untitled h1
table 3

| Mesothelin expression in human cancers by immunohistochemistry  Cancer histology Mesothelin  Expression (%) Comments   | References                                                                           |                                                                                                                                    |                                                                         |
|------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|
| Present in all pleural                                                                                                 |                                                                                      |                                                                                                                                    |                                                                         |
| Mesothelioma                                                                                                           | 100                                                                                  | mesotheliomas; absent  in sarcomatous type                                                                                         | (Chang et al., 1992a:  Or Ordonez, 2003)                                |
| Absent in normal                                                                                                       |                                                                                      |                                                                                                                                    |                                                                         |
| Pancreatic                                                                                                             | 100                                                                                  | pancreas and chronic  pancreatitis                                                                                                 | (Argani et al., 2001;  Hassan et al., 2005b;  Ordóñez, 2003)            |
| Present in nonmucinous ovarian  cancers; absent from  mucinous type                                                                                                                        | (Chang et al., 1992b;  Frierson et al., 2003;  Hassan et al., 2005a;  Ordóñez, 2003) |                                                                                                                                    |                                                                         |
| Ovarian                                                                                                                | 67-100                                                                               | Present in lung  adenocarcinomas and  some expression in  squamous and large  cell lung cancer; absent  in small cell lung  cancer | (Ho et al., 2007;  Miettinen and  Sarlomo-Rikala, 2003;  Ordóñez, 2003) |
| Lung  adenocarcinoma                                                                                                   | 41-53                                                                                |                                                                                                                                    |                                                                         |
| Esophageal                                                                                                             | 25, adenocarcinoma  75, squamous carcinoma                                           | (Ordóñez, 2003)                                                                                                                    |                                                                         |
| Colorectal  adenocarcinoma                                                                                             | 28                                                                                   | (Ordóñez, 2003)                                                                                                                    |                                                                         |
| Cervical                                                                                                               | 25                                                                                   | Uterine, squamous  carcinoma                                                                                                       | (Ordóñez, 2003)                                                         |  
Table 4  
Table 4. Determination of coSS1scFv-CD28Z retroviral vector titers.  
| retroviral vector titers. Harvest   | Titer (TU/mL, x106 )   |
|-------------------------------------|------------------------|
| 1                                   | 1.2 + 0.2              |
| 2                                   | 1.8 + 0.1              |
| 3                                   | 2.1 + 0.2              |
| 4                                   | 2.2 + 0.2              |
| 5                                   | 1.8 + 0.2              |
| 6                                   | 1.8 + 0.1              |
|                                     |                        |
untitled h1
t a ble 5

| T u m or C ell Li n e   |               |         |           |              |           |             |
|-------------------------|---------------|---------|-----------|--------------|-----------|-------------|
| M e s o-                | M e s o +     |         |           |              |           |             |
| P ati e nt              | S a m pl e    | N o n e | A 4 3 1   | A 4 3 1- H 9 | H A Y     | O V C A R 3 |
| Pt. K                   | H ar v e st 1 | 6 3 4   | 1 7 4     | 1 6 2 6 9    | 1 3 4 7 6 | 2 1 0 2 0   |
| H ar v e st 2           | 5 8 3         | 1 6 2   | 3 0 2 2 5 | 2 6 8 0 8    | 3 7 3 9 8 |             |
| H ar v e st 3           | 7 0 5         | 1 9 4   | 3 2 7 7 3 | 3 0 1 1 1    | 4 0 2 4 9 |             |
| H ar v e st 4           | 6 4 2         | 1 8 8   | 3 2 5 8 0 | 2 5 3 4 5    | 3 2 1 3 0 |             |
| H ar v e st 5           | 6 5 7         | 1 9 3   | 2 3 6 2 0 | 1 9 9 6 5    | 2 7 0 8 8 |             |
| H ar v e st 6           | 4 5 1         | 1 3 2   | 2 0 3 0 8 | 1 6 2 3 1    | 2 1 8 0 0 |             |
| Pt. L                   | H ar v e st 1 | 1 1 2   | 1 1 8     | 3 2 7 7 5    | 3 9 5 8   | 2 7 2 1     |
| H ar v e st 2           | 1 1 3         | 1 0 8   | 2 8 4 8 1 | 8 2 5 6      | 4 4 8 6   |             |
| H ar v e st 3           | 9 8           | 1 0 4   | 3 6 6 6 1 | 9 2 0 0      | 4 6 5 6   |             |
| H ar v e st 4           | 1 0 1         | 1 0 0   | 3 6 8 9 3 | 9 9 0 3      | 4 7 0 0   |             |
| H ar v e st 5           | 8 7           | 1 3 5   | 3 6 6 3 5 | 5 1 0 0      | 2 7 1 8   |             |
| H ar v e st 6           | 1 0 2         | 1 2 8   | 2 9 2 8 8 | 4 3 1 4      | 2 5 9 7   |             |
| Pt. M                   | H ar v e st 1 | 1 0 2   | 8 7       | 5 6 8 6      | 2 0 6 8 0 | 2 6 2 1 0   |
| H ar v e st 2           | 9 4           | 9 4     | 1 0 0 4 9 | 2 3 2 6 0    | 1 6 3 3 7 |             |
| H ar v e st 3           | 9 1           | 8 0     | 1 5 0 3 5 | 2 6 6 7 2    | 2 0 7 4 0 |             |
| H ar v e st 4           | 8 6           | 8 4     | 1 4 1 0 3 | 2 4 5 3 6    | 2 2 7 8 4 |             |
| H ar v e st 5           | 1 1 6         | 7 5     | 9 3 5 7   | 2 5 1 6 8    | 2 1 6 6 9 |             |
| H ar v e st 6           | 1 0 8         | 8 4     | 9 8 3 1   | 1 8 1 3 4    | 1 6 4 1 0 |             |  
T a bl e 5. S p e cifi c c yt o ki n e r el e a s e b y C A R-tr a n s d u c e d P B L.  
C yt o ki n e r el e a s e w a s m e a s ur e d f oll o wi n g t h e i n c u b ati o n of 1 0 tr a n s d u c e d T  
l y m p h o c yt e s wit h 1 0 t u m or t ar g et c ell s i n 2 0 0 m L f or 1 8 h at 3 7 C. N e g ati v e t u m or t ar g et, A 4 3 1 a n d m e s ot h eli n- p o siti v e t u m or t ar g et s i n cl u d e A 4 3 1- H 9 (tr a n sf e ct a nt), H A Y  
m e s ot h eli o m a c a n c er c ell li n e) a n d O V C A R 3 ( o v ari a n c a n c er c ell li n e). All c ell li n e s w er e c ult ur e d i n R 1 0 m e di u m c o n si sti n g of R P MI 1 6 4 0 c o nt ai ni n g 1 0 % f et al b o vi n e s er u m. Dil uti o n s of c ult ur e s u p er n at a nt w er e t h e n t e st e d f or I F N g b y e n z y m e-li n k e d i m m u n o s or b e nt a s s a y ( E LI S A). D at a r e pr e s e nt e d fr o m 3 s e p ar at e p ati e nt' s P B L.
untitled h1
table 6 modification of dose

Unless otherwise specified in this protocol, actual body weight is used for dose calculations of treatment agents. In patients who are determined to be obese (BMI > 35), the **practical weight** (see 3 below) will be used. 1. BMI Determination:
BMI = weight (kg) / [height (m)]2 2. Calculation of ideal body weight Male = 50 kg + 2.3 (number of inches over 60 inches)
Example: ideal body weight of 5'10'' male 50 + 2.3 (10) = 73 kg Female = 45.5 kg + 2.3 (number of inches over 60 inches)
Example: ideal body weight of 5'3'' female 45.5 + 2.3 (3) = 57 kg 3. Calculation of "practical weight" Calculate the average of the actual and the ideal body weights. This is the practical weight to be used in calculating the doses of chemotherapy and associated agents designated in the protocol.  
*Practical weight will NOT be used in the calculation of dose for aldesleukin.
untitled h1
figure 1

C.  
ombinant retroviral vector encoding a in. A) *Schematic representation of* eric antigen receptors (CAR) used in this G4S)3 linker to the human CD8D, hinge and ellular T cell signaling domains. B) *Cell* were transduced with the SS1 CAR-encoding PBL were stained for CAR+ cells using a ptavidin-PE. Transduction efficiency in CAR+ cells. Data are from three separate y secreted IFNJ *in response to mesothelin-*1 x 105) and mesothelin-positive target cell
) at 37ºC and 5% CO2. Supernatants were 6$WRGHWHFW,)1Ȗ'DWDUHSUHVHQWDWLYHRI
s controls in all experiments (data not shown).
untitled h1
figure 2

re 2. Expression of mesothelin on human tumor cell lines. Indicated cell lines were incubated recombinant biotinylated MN monoclonal antibody (a mouse anti-human IgG specific for human othelin) or isotype control antibody (mouse IgG) followed by streptavidin-PE. Samples were analyzed ACS. Black histograms indicated staining with the MN antibody and grey histograms , staining wth sotype control.
untitled h1
figure 3

A.  
B. C.  
  
ace expression and functional analysis of CAR-transduced PBL following a A) *Expansion of CAR-transduced PBL.* CAR-transduced PBL (see Figure 1B) were which consists of a second stimulation with OKT3 antibody and cultured at a
/mL in the presence of IL2 and irradiated feeders. On day 5 post-REP, fold ulated. B) *Cell surface expression of SS1 CAR-transduced PBL following a REP.*
, PBL were stained for CAR+ cells using a biotinylated mouse anti-F(ab')2 antibody vidin-PE. Transduction efficiency in transduced PBL was represented as the
+ cells. Data are from the same three separate patient's PBL as in Figure 1B. C)
ed PBL specifically secreted IFNJ *in response to mesothelin-positive tumor cell* ced effector cells (1 x 105) and mesothelin-positive target cell lines (1 x 105) were co-FXOWXUHȝODW&DQG&22. Supernatants were harvested for enzyme-HQWDVVD\(/,6$WRGHWHFW,)1Ȗ'DWDUHSUHVHQWDWLYHRISDWLHQW¶V3%/&'
BL were used as controls in all experiments (data not shown).
untitled h1
appendix 1 '9(56((9(1762&&855112)37(17675(7('7+/'(6/(8.1 (n=525)1

| Body System   | % Patients   | Body System   | % Patients   |         |             |    |    |    |    |
|---------------|--------------|---------------|--------------|---------|-------------|----|----|----|----|
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Appendix 2  
Expected IL-2 Toxicities and their Management  
| Expected IL-2 Toxicities and their Management                                                               |               |                                                                                                                                                 |                                                                  |                   |
|-------------------------------------------------------------------------------------------------------------|---------------|-------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------|-------------------|
| Expected                                                                                                    | Expected      | Supportive                                                                                                                                      | Stop Cycle*                                                      | Stop Treatment ** |
| toxicity                                                                                                    | grade         | Measures                                                                                                                                        |                                                                  |                   |
| Chills                                                                                                      | 3             | IV Meperidine 25-50                                                                                                                             | No                                                               | No                |
| mg, IV q1h, prn,                                                                                            |               |                                                                                                                                                 |                                                                  |                   |
| Fever                                                                                                       | 3             | Acetaminophen 650  mg, po, q4h;  Indomethicin 50-75  mg, po, q8h                                                                                | No                                                               | No                |
| Pruritis                                                                                                    | 3             | Hydroxyzine HCL  10-20 mg po q6h,  prn;  Diphenhydramine  HCL25-50 mg, po,  q4h, prn                                                            | No                                                               | No                |
| Nausea/ Vomiting/                                                                                           | 3             | Ondansetron 10 mg,                                                                                                                              |                                                                  |                   |
| Anorexia                                                                                                    | IV, q8h, prn; |                                                                                                                                                 |                                                                  |                   |
| Granisetron 0.01                                                                                            |               |                                                                                                                                                 |                                                                  |                   |
| mg/kg IV daily prn;  Droperidol 1 mg, IV  q4-6h, prn;  Prochlorperazine 25  mg pr, prn or 10 mg  IV q6h prn | No            | No                                                                                                                                              |                                                                  |                   |
| Diarrhea                                                                                                    | 3             | Loperamide 2mg, po,  q3h, prn;  Diphenoxylate HCl  2.5 mg and atropine  sulfate 25 mcg, po,  q3h, prn; codeine  sulfate 30-60 mg, po,  q4h, prn | If uncontrolled after  24 hours despite all  supportive measures | No                |
| Malaise                                                                                                     | 3 or 4        | Bedrest                                                                                                                                         | If other toxicities  occur  simultaneously                       | No                |
| Hyperbilirubinemia                                                                                          | 3 or 4        | Observation                                                                                                                                     | If other toxicities  occur  simultaneously                       | No                |
| Anemia                                                                                                      | 3 or 4        | Transfusion with                                                                                                                                | If uncontrolled                                                  |                   |
| PRBCs                                                                                                       | despite all   |                                                                                                                                                 |                                                                  |                   |
| supportive measures                                                                                         | No            |                                                                                                                                                 |                                                                  |                   |
| Thrombocytopenia                                                                                            | 3 or 4        | Transfusion with                                                                                                                                | If uncontrolled                                                  |                   |
| platelets                                                                                                   | despite all   |                                                                                                                                                 |                                                                  |                   |
| supportive measures                                                                                         | No            |                                                                                                                                                 |                                                                  |                   |
| Edema/Weight gain                                                                                           | 3             | Diuretics prn                                                                                                                                   | No                                                               | No                |
| Hypotension                                                                                                 | 3             | Fluid resuscitation                                                                                                                             | If uncontrolled                                                  |                   |
| Vasopressor support                                                                                         | despite all   |                                                                                                                                                 |                                                                  |                   |
| supportive measures                                                                                         | No            |                                                                                                                                                 |                                                                  |                   |  
12-C-0111 71  
| Version Date: April 12, 2018                                                                                                       |                                             |                                            |                              |                           |
|------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------|--------------------------------------------|------------------------------|---------------------------|
| Dyspnea                                                                                                                            | 3 or 4                                      | Oxygen or ventilatory                      | If requires                  | No                        |
| support                                                                                                                            | ventilatory support                         |                                            |                              |                           |
| Oliguria                                                                                                                           | 3 or 4                                      | Fluid boluses or  dopamine at renal  doses | If uncontrolled  despite all |                           |
| supportive measures                                                                                                                | No                                          |                                            |                              |                           |
| Increased creatinine                                                                                                               | 3 or 4                                      | Observation                                | Yes (grade 4)                | No                        |
| Renal failure                                                                                                                      | 3 or 4                                      | Dialysis                                   | Yes                          | Yes                       |
| Pleural effusion                                                                                                                   | 3                                           | Thoracentesis                              | If uncontrolled  despite all |                           |
| supportive measures                                                                                                                | No                                          |                                            |                              |                           |
| Bowel perforation                                                                                                                  | 3                                           | Surgical intervention                      | Yes                          | Yes                       |
| Confusion                                                                                                                          | 3                                           | Observation                                | Yes                          | No                        |
| Somnolence                                                                                                                         | 3 or 4                                      | Intubation for airway                      | Yes                          | Yes                       |
| protection                                                                                                                         |                                             |                                            |                              |                           |
| Arrhythmia                                                                                                                         | 3                                           | Correction of fluid  and electrolyte       |                              |                           |
| imbalances; chemical  conversion or  electrical conversion  therapy                                                                | If uncontrolled  despite all                |                                            |                              |                           |
| supportive measures                                                                                                                | No                                          |                                            |                              |                           |
| Elevated Troponin                                                                                                                  | 3 or 4                                      | Observation                                | Yes                          | If changes in LV function |
| levels                                                                                                                             | have not improved to  baseline by next dose |                                            |                              |                           |
| Myocardial                                                                                                                         | 4                                           | Supportive care                            | Yes                          | Yes                       |
| Infarction  Elevated                                                                                                               | 3 or 4                                      | Observation                                | For grade 4 without          | If changes have not       |
| transaminases                                                                                                                      | liver metastases                            | improved to baseline by  next dose         |                              |                           |
| Hyperbilirubinemia                                                                                                                 | 3 or 4                                      | Observation                                | For grade 4 without          | If changes have not       |
| liver metastases                                                                                                                   | improved to baseline by  next dose          |                                            |                              |                           |
| Electrolyte                                                                                                                        | 3 or 4                                      | Electrolyte                                | If uncontrolled              |                           |
| imbalances                                                                                                                         | replacement                                 | despite all                                |                              |                           |
| supportive measures                                                                                                                | No                                          |                                            |                              |                           |
| Neutropenia                                                                                                                        | 4                                           | Observation                                | No                           | No                        |
| *Unless the toxicity is not reversed within 12 hours  ** Unless the toxicity is not reversed to grade 2 or less by next treatment. |                                             |                                            |                              |                           |
untitled h1
appendix 3 interleukin-2 toxicities observed

| Table 8. Toxicity of Treatment with Interleukin-2   |       |     |       |      |     |     |     |       |
|-----------------------------------------------------|-------|-----|-------|------|-----|-----|-----|-------|
| Interleukin-2 Plus                                  | Alone | TNF | a-IFN | MoAB | CYT | LAK | til | Total |
| Number of Patients                                  | 155   | 38  | 128   | 32   | 19  | 214 | 66  | 652*  |
| Number of Courses                                   | 236   | 85  | 210   | 35   | 30  | 348 | 95  | 1039  |
| Chills                                              | 75    | 16  | 68    | 8    | 8   | 191 | 33  | 39    |
| 53                                                  | 9     | 26  | 2     | 2    | 82  | 180 |     |       |
| Pruntus                                             | , 6   |     |       |      |     |     |     |       |
| Necrosis                                            | 3     | l   | 1.2   | l    | l   | l   | l   | .5    |
| Anaphylaxis                                         | l     | l   | l     |      |     |     |     |       |
| l                                                   | l     | l   |       |      |     |     |     |       |
| Mucositis (requiring liquid diet)                   | 6     | 1   | 7     | 2    | 12  | 2   | 30  |       |
| Alimentation not possible                           | i     | 1   | 4     |      |     |     |     |       |
|                                                     |       | 2   | l     |      |     |     |     |       |
| 162                                                 | 42    | 17  | 14    | 20   | 263 | 48  | 666 |       |
| Nausea and vomiting                                 |       |     |       |      |     |     |     |       |
| Diarrhea                                            | 144   | 38  | 98    | 15   | 13  | 250 | 38  | 596   |
| Hyperbilirubinemia (maximum/mg %)                   | 126   | 49  | 97    | 21   | 18  | 190 | 46  | 547   |
| 2.1-6.0                                             |       |     |       |      |     |     |     |       |
| 6.1-10.0                                            | 12    | 179 |       |      |     |     |     |       |
| 49                                                  | 3     | 8   | 9     | 72   | 26  |     |     |       |
| 10.1+                                               | 26    | 1   | 4     | 3    | l   | 40  | 8   | 83    |
| Oliguria                                            |       |     |       |      |     |     |     |       |
| <80 ml/8 hours                                      | 37    | 9   | 25    | 347  |     |     |     |       |
| 81                                                  | 67    | 14  | 14    |      |     |     |     |       |
| <240 ml/24 hours                                    | 19    | 2   | 3     | l    | 12  | s   | 42  |       |
| Weight gain (% body weight)                         |       |     |       |      |     |     |     |       |
| 0.0–5.0                                             | 23    | 9   | 377   |      |     |     |     |       |
| 106                                                 | 65    | 8   | 17    | 49   |     |     |     |       |
| 5.1-10.0                                            | 78    | 41  | 11    | 22   | 10  | 148 | 26  | 436   |
| 10.1-15.0                                           | 43    | 17  | 26    | 3    | 9   | 62  | 15  | 175   |
| 15.1-20.0                                           | 7     | 3   | 8     | I    | l   | 15  | 3   | 38    |
| 2                                                   | l     | 2   | 13    |      |     |     |     |       |
| 20.1+                                               | I     | l   | 6     |      |     |     |     |       |
| Elevated creatinine (maximum/mg %)                  |       |     |       |      |     |     |     |       |
| 2.1-6.0                                             | 148   | 43  | 121   | 20   | 14  | 237 | 54  | 637   |
| 6.1-10.0                                            | 21    | I   | 14    | 3    | 34  | 12  | 85  |       |
| 10.1+                                               | S     | l   | i     | l    | 2   | l   | 10  |       |
| Hematuria (gross)                                   | 2     | 2   |       |      |     |     |     |       |
| l                                                   | l     | l   | a     | l    |     |     |     |       |
| Edema (symptomatic nerve or vessel                  | 4     | 6.  | 7     | 17   |     |     |     |       |
| compression)                                        | l     | l   | l     |      |     |     |     |       |
| Tissue ischemia                                     | l     | l   | i     | I    | l   | 1.2 |     |       |
| i                                                   |       |     |       |      |     |     |     |       |
| Resp. distress:                                     |       |     |       |      |     |     |     |       |
| not intubated                                       | 17    | i   | 9     | 4    | l   | 28  | 7   | 67    |
| s                                                   |       |     |       |      |     |     |     |       |
| intubated                                           | 15    | i   | 6     | 3    | 12  | 41  |     |       |
| Bronchospasm                                        | 2     | I   | 2     | l    | 4   | 9   |     |       |
| Pleural effusion (requiring                         |       |     |       |      |     |     |     |       |
| thoracentesis)                                      | 4     | l   | i     | 2    | 8   | i   | 17  |       |
| Somnolence                                          | 29    | 2   | 2     | 45   | 8   | 14  |     |       |
| 6                                                   | 2     |     |       |      |     |     |     |       |
| Coma                                                | 9     | i   | 8     | 2    | .8  | s   | 33  |       |
| l                                                   |       |     |       |      |     |     |     |       |
| Disorientation                                      | 52    | 3   | 50    | 7    | 4   | 89  | 10  | 215   |
| Hypotension (requiring pressors)                    | 19    | 16  | 40    | 17   | 12  | 259 | 45  | .508  |
| Angina                                              | 5     | -   | 8     |      | 8   | 22  |     |       |
| Myocardial infarction                               | 4     | I   | l     | l    | l   |     | 6   |       |
| Arrythmias                                          | 15    | 2   | 13    | 3    | l   | 39  | 6   | 78    |
| Anemia requiring transfusion (number                |       |     |       |      |     |     |     |       |
| units transfused)                                   |       |     |       |      |     |     |     |       |
| 1-15                                                | 77    | 16  | 53    | 9    | 6   | 176 | 40  | 377   |
| 6-10                                                | 22    | -   | 5     | 3    | 2   | 53  | 9   | 95    |
| 1-15                                                | 4     | l   | l     | l    | l   | 15  | 4   | 24    |
| 16+                                                 | i     | l   | 1     | l    | l   | .11 | 1.1 | 14    |
| Thrombocytopenia (minimum/mm3)                      |       |     |       |      |     |     |     |       |
| <20,000                                             | 28    | I   | 2     | 4    | 6   | 71  | 19  | 131   |
| 20,001-60,000                                       | 82    | 1   | 62    | 14   | 12  | 150 | 30  | 361   |
| 60,001-100,000                                      | 53    | 36  | 76    | 11   | 8   | 79  | 2   | 285   |
| Central line sepsis                                 | 13    | 7   | I     | 4    | 36  | 2   | 63  |       |
| Death                                               | 4     | l   | 1     | 3    | 2   | 10  |     |       |
| l                                                   | l     |     |       |      |     |     |     |       |
| * Eleven patients are in two protocols.             |       |     |       |      |     |     |     |       |
untitled h1
certificate of analysis infused t

Date of preparation of final product: Patient:
Tests performed on final product:  
| Test                                                                                                                                                                                                        | Method                                              | Limits             | Result   | Tests  Performed   | Initials   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------|--------------------|----------|--------------------|------------|
| by                                                                                                                                                                                                          | /Date                                               |                    |          |                    |            |
| Cell viability1                                                                                                                                                                                             | trypan blue exclusion                               | >70%               |          |                    |            |
| Total viable cell                                                                                                                                                                                           | visual microscopic count                            | Between 106  and   |          |                    |            |
| number1                                                                                                                                                                                                     | 5 x 1010 cells                                      |                    |          |                    |            |
| Identity                                                                                                                                                                                                    | FACs analysis on final                              | > 80 % CD3+ after  |          |                    |            |
| expanded cells7                                                                                                                                                                                             | transduction                                        |                    |          |                    |            |
| Tumor reactivity2                                                                                                                                                                                           | J-IFN release vs. cell  line expressing  mesothelin | >200 pg/ml and > 2 |          |                    |            |
| times background                                                                                                                                                                                            |                                                     |                    |          |                    |            |
| CAR expression2                                                                                                                                                                                             | FACS analysis of the                                | PBL, >30%          |          |                    |            |
| transduced cells  gram stain1,3,                                                                                                                                                                            | no micro-organisms                                  |                    |          |                    |            |
| Microbiological                                                                                                                                                                                             |                                                     |                    |          |                    |            |
| studies                                                                                                                                                                                                     | seen                                                |                    |          |                    |            |
|                                                                                                                                                                                                             | aerobic culture3,4                                  | no growth          |          |                    |            |
|                                                                                                                                                                                                             | fungal culture3,4                                   | no growth          |          |                    |            |
|                                                                                                                                                                                                             | anaerobic culture3,4                                | no growth          |          |                    |            |
|                                                                                                                                                                                                             | mycoplasma test5                                    | negative           |          |                    |            |
| Endotoxin                                                                                                                                                                                                   | limulus assay1                                      | "(8NJ                    |          |                    |            |
| RCR                                                                                                                                                                                                         | S+L- Assay4                                         |                    |          |                    |            |
| RCR-PCR6                                                                                                                                                                                                    | negative                                            |                    |          |                    |            |
| 1 Performed on sample of the final product immediately prior to infusion. Results are available at the time of infusion. 2 Performed 2-10 post transduction. Results are available at the time of infusion. |                                                     |                    |          |                    |            |  
1 Performed on sample of the final product immediately prior to infusion. Results are available at the time of infusion. 2 Performed 2-10 post transduction. Results are available at the time of infusion.  
3 Performed 2-4 days prior to infusion. Results are available at the time of infusion but may not be definitive.  
4 Sample collected from the final product prior to infusion. Results will not be available before cells are infused into the patient. 5 Performed 2-10 days prior to infusion. Results are available at the time of infusion.  
6 Performed on sample approximately 1-4 days prior to infusion. Results are available at the time of infusion.  
7 Performed 2-10 days prior to infusion. Results are available at the time of infusion. REP cells well be tested if intended for infusion.  
Prepared by: _________________________________________ Date: ____________________  
  
QC sign-off: __________________________________________ Date: ____________________  
  
Qualified Laboratory or Clinical Supervisor