**Update on retroviral vector-mediated tumorigenesis**

**in gene transfer clinical trials**

**ERRATUM (modifications shown in *bold, italic*)**

**Appendix 4.**

**Table 1. Comparison of X-SCID Retroviral Vector-Mediated Gene
Transfer**

+-----------------+------------+------------+------------+------------+
| **C             | **Fischer  | **Thrasher | **We       | **         |
| haracteristic** | \[1\]**    | \[2\]**    | inberg\*** | Malech\*** |
+-----------------+------------+------------+------------+------------+
| Cell Source     | Bone       | Bone       | Bone       | ***G-CSF   |
|                 | Marrow     | Marrow     | Marrow     | mobilized  |
|                 |            |            |            | CD34+      |
|                 |            |            |            | PBSC***    |
+-----------------+------------+------------+------------+------------+
| CD34^+^         | Miltenyi   | CliniMACS  | Isolex 300 | Isolex     |
| Selection       | Biotec     |            | I          | 300I       |
+-----------------+------------+------------+------------+------------+
| Media           | X-Vivo-10  | X-Vivo-10  | X-vivo-15  | X-Vivo 10  |
+-----------------+------------+------------+------------+------------+
| Serum/Other     | 4% FCS     | 1% HSA     | None       | 1% HSA     |
+-----------------+------------+------------+------------+------------+
| Cytokines       | 300 ng/ml  | 300 ng/ml  | 300 ng/ml  | 50 ng/ml   |
| (Source):       | (Immunex)  | (R&D)      |            |            |
|                 |            |            | (Immunex)  | (R&D)      |
| 1.  Flt-3       | 60 ng/ml   | 20 ng/ml   |            |            |
|     ligand      | (Novartis) | (R&D)      | \-\        | 5 ng/ml    |
|                 |            |            | -\-\-\-\-\ |            |
| 2.  IL-3        | \          | 100 ng/ml  | -\-\-\-\-- | (R&D)      |
|                 | -\-\-\-\-\ |            |            |            |
| 3.  TPO         | -\-\-\-\-- | (R&D)      | 50 ng/ml   | 50 ng/ml   |
|                 |            |            |            |            |
| 4.  MGDF        | 100 ng/ml  | \-\        | (R&D)      | (R&D)      |
|                 | (Amgen)    | -\-\-\-\-\ |            |            |
| 5.  SCF         |            | -\-\-\-\-- | \          | \-\-\-\    |
|                 | 300 ng/ml  |            | -\-\-\-\-\ | -\-\-\-\-\ |
| 6.  IL-6        |            | 300 ng/ml  | -\-\-\-\-- | -\-\-\-\-- |
|                 | (Amgen)    |            |            |            |
|                 |            | (R&D)      | 50 ng/ml   | 50 ng/ml   |
|                 | \-\        |            |            |            |
|                 | -\-\-\-\-\ | \-\        | (R&D)      | (R&D)      |
|                 | -\-\-\-\-- | -\-\-\-\-\ |            |            |
|                 |            | -\-\-\-\-- | \-\        | 25 ng/ml   |
|                 |            |            | -\-\-\-\-\ |            |
|                 |            |            | -\-\-\-\-- | (R&D)      |
+-----------------+------------+------------+------------+------------+
| Hrs Prestim.    | 24         | 40         | 40         | 18         |
+-----------------+------------+------------+------------+------------+
| Transduction    | Yes        | Yes        | Yes        | Yes        |
|                 |            |            |            |            |
| 1.  Fibronectin | Three      | Three      | Three      | Four       |
|                 |            |            |            |            |
| 2.  Exposures   | 72 hours   | 56 hours   | 72 hours   | 78 hours   |
|                 |            |            |            |            |
| 3.  Time        |            |            |            |            |
+-----------------+------------+------------+------------+------------+
| Vector Backbone | MFG        | MFG        | MND        | MFG        |
|                 |            |            |            |            |
| (LTR)           | (MoMLV     | (MoMLV     | (MPSV LTR) | (MoMLV     |
|                 | LTR)       | LTR)       |            | LTR)       |
+-----------------+------------+------------+------------+------------+
| Vector Envelope | A-MuLV     | GaLV       | GaLV       | GaLV       |
| (Packaging      |            |            |            |            |
| Line)           | (Psi-CRIP) | (PG-13)    | (PG-13)    | (PG13)     |
+-----------------+------------+------------+------------+------------+

1\. Hacein-Bey-Abina, S., et al., *Sustained correction of X-linked
severe combined immunodeficiency by ex vivo gene therapy.* New England
Journal of Medicine, 2002. **346**(16): p. 1185-1193.

2\. Gaspar, H.B., et al., *Gene therapy of X-linked severe combined
immunodeficiency by use of a pseudotyped gammaretroviral vector.*
Lancet, 2004. **364**(9452): p. 2181-7.

\* Details provided with kind permission from Drs. Weinberg and
Podsakoff of The Saban Research Institute of Childrens Hospital Los
Angeles, and Dr. Malech of NIH/NIAID.

**Table 4. Clinical Summary of ADA-SCID Trials**

+--------------+--------------+-------------+------------+-----------+
| **In         | **Previous   | **Previous  | **Max Dose | **Longest |
| vestigator** | BMT/**       | infectious  | transpla   | time from |
|              |              | or**        | ntedADA^+^ | tr        |
|              | **Co         |             | cells/kg** | eatment** |
|              | nditioning** | **other     |            |           |
|              |              | comp        |            |           |
|              |              | lications** |            |           |
+--------------+--------------+-------------+------------+-----------+
| **Bord       | 1 of 2       | Yes         | 2.15 x     | Approx    |
| ignon\[3\]** | subjects     |             | 10^6^      | 3.5 years |
|              |              |             |            |           |
|              | Busulfan     |             |            |           |
|              | conditioning |             |            |           |
+--------------+--------------+-------------+------------+-----------+
| **Kohn\***   | ***No        | No          | 6.67 x     | ***3.5    |
|              | Previous     |             | 10^6^      | years***  |
|              | BMT***       |             |            |           |
|              |              |             |            |           |
|              | No           |             |            |           |
|              | conditioning |             |            |           |
+--------------+--------------+-------------+------------+-----------+

3\. Aiuti, A., et al., *Gene therapy for adenosine deaminase
deficiency.* Curr Opin Allergy Clin Immunol, 2003. **3**(6): p. 461-6.

\*Details provided with kind permission from Drs. Kohn and Podsakoff of
The Saban Research Institute of Children's Hospital Los Angeles.
Conditions reflect methods used since 2001, not previously.