Document:

<PAGE>   1
                                                                 EXHIBIT 10.8(c)

                                AMENDMENT NO. 2
                                     TO THE
                    PATENT AND TECHNOLOGY LICENSE AGREEMENT

     This is AMENDMENT NO. 2 effective this 8th day of August, 1997, ("EFFECTIVE
AMENDMENT NO. 2 DATE") to the Patent and Technology License Agreement dated
July 20, 1994, as amended by that certain Amendment No. 1 effective September
1, 1996 (HEREINAFTER REFERRED TO AS THE "FIRST AMENDED AGREEMENT"), by and
between THE UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTER (hereinafter
referred to as "MDA"), located at Houston, Texas, and which is a component
institution of THE UNIVERSITY OF TEXAS SYSTEM (hereinafter referred to as
"SYSTEM") which is governed by a BOARD OF REGENTS (hereinafter referred to as
"BOARD") and INTROGEN THERAPEUTICS, INC., located at 301 Congress Avenue, Suite
1850, Austin, Texas 78701 (hereinafter referred to as "LICENSEE").

                                    RECITALS

A.   BOARD is the owner of the invention(s) and other subject matter listed in
     SCHEDULE B hereto ("IL-2 INVENTION(s)").

B.   LICENSEE is a company interested in the development and commercialization
     of new technologies directed to the treatment of cancer, and other
     threatening diseases, to which end LICENSEE, MDA and BOARD entered into the
     FIRST AMENDED AGREEMENT noted hereinabove.

C.   LICENSEE wishes to add the IL-2 INVENTIONS to the LICENSED SUBJECT MATTER
     under the FIRST AMENDED AGREEMENT.

D.   BOARD wishes to grant LICENSEE rights to the IL-2 INVENTIONS under the
     FIRST AMENDED AGREEMENT to promote its practical development for the
     benefit of the MDA's patients and for the benefit of the people of the
     state of Texas.

E.   The definitions set forth in the AGREEMENT and the FIRST AMENDED AGREEMENT
     shall apply in this AMENDMENT NO. 2, except to the extent that a definition
     herein is specific to this AMENDMENT No. 2.

NOW, THEREFORE, in consideration for the mutual covenants contained herein,
the sufficiency of which is hereby acknowledged, the parties hereby agree to
the following:
<PAGE>   2
THE FIRST AMENDED AGREEMENT IS HEREBY AMENDED AS FOLLOWS:
AMENDED TERMS

1.   Add the following as new Schedule B in its entirety:

                                  SCHEDULE B
                                IL-2 INVENTIONS

[*]
[*]
Inventors: [*]
U.S. Patent Number: [*]
PCT Patent Number: [*]

2.   So much of Section 2.3(a) as reads

     "...the patents and patent applications described in Schedule A hereto (the
     "Existing Patent Rights") and all patents anywhere in the world issuing
     thereon;"

     is hereby amended to read

     "...the patent and patent applications described in Schedules A and B
     hereto (the "Existing Patent Rights") and all patents anywhere in the world
     issuing thereon;"

3.   The title for ATTACHMENT A of the AGREEMENT shall be replaced in its
     entirety to read as follows: "SCHEDULE A."

4.   Add new paragraph 2.12 that will read in its entirety as follows:

     "2.12 IL-2 PRODUCT shall mean a LICENSED PRODUCT the manufacture, use or
     sale of which would infringe a VALID CLAIM within the IL-2 PATENTS."

5.   Add new paragraph 2.13 that will read in its entirety as follows:

     "2.13 IL-2 PATENTS shall mean those PATENT RIGHTS which claim or disclose
     an IL-2 INVENTION as described in Schedule B hereto."

6.   Paragraph 5.1 of the AGREEMENT shall be amended by the addition of the
     following two new paragraphs:

     [*] Certain information on this page has been omitted and filed separately
         with the Commission. Confidential treatment has been requested with
         respect to the omitted portions.

                                       2
<PAGE>   3

         New 5.1(e) shall read in its entirety:

         "(e) [*] of NET SALES attributed to SALES of LICENSED
         PRODUCTS that are IL-2 PRODUCTS by LICENSEE, AFFILIATES, and
         SUBLICENSEES." For avoidance of doubt, the royalties due on PRODUCTS
         other than IL-2 PRODUCTS shall be as specified in Paragraph 5.1(a)
         above.

         New 5.1(f) shall read in its entirety:

         "(f) For any advance payment attributable to an IL-2 PRODUCT or IL-2
         PATENT received by LICENSEE from a third party pursuant to a
         sublicensee, marketing, distribution, or franchise agreement, other
         than amount paid to LICENSEE in reimbursement of development or other
         costs, as provided for in Article 4.3 hereof [*]: [*] of said advance
         payment attributable to an IL-2 PRODUCT or IL-2 PATENT." For avoidance
         of doubt, advanced payments for PRODUCTS other than IL-2 PRODUCTS shall
         be as specified in Paragraph 5.1(b) above.

7.       The definition of TECHNOLOGY RIGHTS (Paragraph 2.4) shall be amended by
         addition of the following text:

         "TECHNOLOGY RIGHTS shall also include all information, know-how,
         biological materials or other subject matter owned by the BOARD and
         reasonably necessary for practicing an IL-2 INVENTION at any time
         covered by the IL-2 PATENTS."

         OTHERWISE, the terms and provisions of the original AGREEMENT shall
remain in full force and effect, provided, however, that in the event of a
conflict in the terms and conditions between this AMENDMENT NO. 2 and the
AGREEMENT, the terms and conditionals of this AMENDMENT NO. 2 shall prevail.
THIS AMENDMENT NO. 2 and the SCHEDULES hereto and the AGREEMENT and its
ATTACHMENTS constitute the entire agreement between the parties in connection
with the subject matter hereof and thereof and supersede all prior and
contemporaneous agreements, understandings, negotiations and discussions,
whether oral or written, of the parties.

        [*] Certain information on this page has been omitted and filed
            separately with the Commission. Confidential treatment has been
            requested with respect to the omitted portions.

                                       3
<PAGE>   4

         IN WITNESS WHEREOF, the parties hereto have caused their duly
authorized representatives to execute this AMENDMENT NO. 2.

THE UNIVERSITY OF TEXAS                 BOARD OF REGENTS OF THE
M.D. ANDERSON CANCER CENTER             UNIVERSITY OF TEXAS SYSTEM

By   /s/ MICHAEL J. BEST                By  /s/ RAY FARABEE
  -----------------------------           --------------------------
  Michael J. Best                         Ray Farabee
                                          Vice Chancellor and General Counsel

APPROVED AS TO CONTENT                  APPROVED AS TO FORM

By   /s/ WILLIAM J. DOTY                By  /s/ BETH LYNN MAXWELL
  -----------------------------           --------------------------
  William J. Doty                         Beth Lynn Maxwell, Ph.D.
  Director, Technology Development        Office of General Counsel

INTROGEN THERAPEUTICS, INC.

By   /s/ DAVID G. NANCE
  -----------------------------
  David G. Nance
  President

                                       4
<PAGE>   5
                                   SCHEDULE B
                                IL-2 INVENTIONS

                                      [*]
                                      [*]
                                 Inventors: [*]
                      U.S. Patent Number: [*] Issued: [*]
                             PCT Patent Number: [*]

    [*] Certain information on this page has been omitted and filed separately
        with the Commission. Confidential treatment has been requested with
        respect to the omitted portions.

                                       5<PAGE>   1
                                                                    Exhibit 10.9

CS93-27

                 SPONSORED RESEARCH AGREEMENT FOR CLINICAL STUDY

         Agreement, made this 11th day of February, 1993, by and between THE
UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTER (hereinafter referred to as
"CANCER CENTER"), a component institution of The University of Texas System
(hereinafter referred to as "SYSTEM"), located in Houston, Texas, and Texas
Biomedical Development Partners (hereinafter referred to as "SPONSOR"), located
in Austin, Texas.

                                   WITNESSETH:

         WHEREAS, CANCER CENTER has research facilities and situations which
would allow clinical investigation and study of the "Clinical Protocol for
Modification of Oncogene and tumor Suppressor Gene Expression in Non-Small Cell
Lung Cancer (NSCLC)" as described in Exhibit I hereinafter referred to as
("Research"), a copy of which is attached hereto and incorporated herein by
reference; and

         WHEREAS, both SPONSOR and CANCER CENTER consider it necessary and
desirable and desirable to perform the Research;

         NOW, THEREFORE, the parties agree as follows:

1. Evaluation. SPONSOR agrees to engage the services of CANCER CENTER as an
independent contractor to perform the Research. The Research will be under the
supervision of Jack A. Roth, M.D. (Principal Investigator) at CANCER CENTER,
with the assistance of appropriate associates and colleagues at CANCER CENTER as
may be required.

2. Research. CANCER CENTER agrees as an independent contractor to conduct the
Research. Such Research was originally approved by CANCER CENTER in accordance
with CANCER CENTER policy and may be subsequently amended only in accordance
with CANCER CENTER policy and the written agreement of CANCER CENTER and SPONSOR
as provided for in Article 15 herein below.

3. Invention and Patents.

         a. For all purposes herein, "Invention" shall mean any discovery,
concept or idea whether or not patentable or copyrightable, which (i) arises out
of work performed pursuant to the obligations of this Agreement; (ii) is
conceived and reduced to practice during the term of the Agreement as defined in
Article 13 hereinbelow; and (iii) includes but is not limited to processes,
methods, software, formulae, techniques, compositions of matter, devices, and
improvements thereof and know-how relating thereto. Inventions made solely by
the Principal Investigator and/or other CANCER CENTER personnel as identified in
Article 1 hereinabove or agents of CANCER CENTER shall be the sole property of
CANCER CENTER.

         b. In the event that an Invention is made, CANCER CENTER agrees to
include such Invention in the Option Agreement of December 17, 1992 (attached
hereto as Exhibit III) previously
<PAGE>   2
entered in to by CANCER CENTER and SPONSOR and give notice of such Invention to
SPONSOR within thirty (30) days of the identification of such Invention.

4. Confidentiality. In the course of work performed pursuant to the Research
under this Agreement, should either party provide confidential information to
the other party, the recipient party shall, until three (3) years after the
termination of this Agreement, maintain the confidentiality of that information
as it maintains the confidentiality of its own confidential information, and
shall not disclose such confidential information to any other party, nor shall
the recipient party disclose the disclosing party's confidential information to
the recipient's employees other than those employees having a "need-to-know."
Confidential information shall be clearly marked as such. If disclosed orally,
the party making the disclosure shall be responsible for clearly informing the
recipient party of the confidentiality of the information disclosed.
Notwithstanding the other provisions of this paragraph, nothing disclosed
hereunder shall be construed as confidential information which:

         a. is or becomes available to the public (except by a breach of this
Agreement by a party hereto);

         b. is rightfully received from another party not under obligation of
confidentiality to the disclosing party;

         c. is not known by the recipient party, or is independently developed
by the recipient party by persons without access to the confidential
information;

         d. is approved for release by the party designating the information as
confidential;

         e. is not identified as confidential at the time of disclosure;

         f. is not in writing or physical form at time of disclosure or reduced
to a written or physical form and identified as confidential within thirty (30)
days of disclosure; or

         g. is required to be disclosed under the laws of the United States of
America or the State of Texas or other governmental bodies, provided that the
parties shall first exhaust all reasonable measures available to protect the
confidentiality of such information upon disclosure.

5. Publication Rights. Notwithstanding the provisions of Article 4 of this
Agreement, CANCER CENTER may publish scientific papers relating to the
collaborative research performed under this Agreement. In the event that CANCER
CENTER wishes to publish, CANCER CENTER shall notify SPONSOR of its desire to
publish [ * ] in advance of publication and shall furnish to SPONSOR a written
description of the subject matter of the publication in order to permit SPONSOR
to review and comment thereon.

6. Publicity. CANCER CENTER acknowledges SPONSOR'S intention to distribute
periodically information releases and announcements to the news media regarding
the progress of research hereunder. SPONSOR shall not release such materials
containing the name of CANCER CENTER or any of its employees without prior
written approval by an authorized representative of CANCER CENTER, and

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                      -2-
<PAGE>   3
said approval shall not be unreasonably withheld. Should CANCER CENTER reject
the news release, CANCER CENTER and SPONSOR agree to discuss the reasons for
CANCER CENTER's rejection, and every effort shall be made to develop an
appropriate informational news release within the bounds of accepted academic
practices. SPONSOR reserves the same right in the event that CANCER CENTER
desires to distribute a news release concerning the research program. Nothing
herein shall be construed as prohibiting CANCER CENTER or SPONSOR from reporting
on this study to a governmental agency.

7. Responsibility. The parties each agree to assume individual responsibility
for the actions and omissions of their respective employee, agents and assigns
in conjunction with this evaluation.

8. Independent Contractor. SPONSOR will not have the right to direct or control
the activities of CANCER CENTER in performing the services provided herein, and
CANCER CENTER shall perform services hereunder only as an independent
contractor, and nothing herein contained shall be construed to be inconsistent
with this relationship or status. Under no circumstances shall CANCER CENTER be
considered to be an employee or agent of SPONSOR. This Agreement shall not
constitute, create or in any way be interpreted as a joint venture, partnership
or formal business organization of any kind.

9. Title to Equipment. CANCER CENTER shall retain title to all equipment
purchased and/or fabricated by it with funds provided by SPONSOR under this
Agreement.

10. Survivorship. The provisions of Articles 3, 4, 5, 6, and 12 shall survive
any expiration or termination of this Agreement.

11. Assignment. This Agreement may not be assigned by either party without the
prior written consent of the other party; provided, however, that SPONSOR may
assign this Agreement to any purchaser or transferee of all or substantially all
of SPONSOR's business upon prior written notice to CANCER CENTER.

12. Indemnification. CANCER CENTER shall, to the extent authorized under the
Constitution and the laws of the State of Texas, hold SPONSOR harmless from
liability resulting from the negligent acts or omissions of CANCER CENTER, its
agents or employees pertaining to the activities to be carried out pursuant to
the obligations of this Agreement; provided, however, that CANCER CENTER shall
not hold SPONSOR harmless from claims arising out of the negligence of SPONSOR,
its officers, agents or any person or entity not subject to CANCER CENTER's
supervision or control.

SPONSOR shall indemnify and hold harmless SYSTEM, CANCER CENTER, their regents,
officers, agents and employees from any liability or loss resulting from
judgments or claims against them arising out of the activities to be carried out
pursuant to the obligations of this Agreement or the use by SPONSOR of the
results of the Research, provided, however, that the following is excluded from
SPONSOR's obligation to indemnify and hold harmless:

         a. the negligent failure of CANCER CENTER to comply with any applicable
governmental requirements; or

                                       -3-
<PAGE>   4
         b. the negligence or willful malfeasance by a regent, officer, agent or
employee of CANCER CENTER or SYSTEM.

13. Award. SPONSOR agrees to pay CANCER CENTER a fee of [ * ]. This fee, as
shown [ * ] in Exhibit II, which is attached hereto and is incorporated herein
by reference, for information only, shall be payable [ * ].

14. Basic Term. This Agreement shall become effective as of the date first
hereinabove written and unless earlier terminated as hereinafter provided, shall
continue in force for a period of Eighteen (18) months after the same.

15. Default and Termination. In the event that either party to this Agreement
shall be in default of any of its material obligations hereunder and shall fail
to remedy such default within [*] after receipt of written notice thereof, the
party not in default shall have the option of terminating this Agreement by
giving written notice thereof, notwithstanding anything to the contrary
contained in this Agreement. Termination of this Agreement shall not affect the
rights and obligations of the parties which accrued prior to the effective date
of termination. SPONSOR shall pay CANCER CENTER for all reasonable expenses
incurred or committed to be expended as of the effective termination date,
subject to the maximum amount as specified in Article 13.

16. Entire Agreement. The parties acknowledge that this Agreement and the
attached Exhibits hereto represent the sole and entire Agreement between the
parties hereto pertaining to the Research and that such supersedes all prior
Agreements, understandings, negotiations and discussions between the parties
regarding same, whether oral or written. There are no warranties,
representations or other Agreements between the parties in connection with the
subject matter hereof except as specifically set forth herein. No supplement,
amendment, alteration, modification, waiver or termination of this Agreement
shall be binding unless executed in writing by the parties hereto.

17. Reform of Agreement. If any provision of this Agreement is, becomes or is
deemed invalid, illegal or unenforceable in any United States jurisdiction, such
provision shall be deemed amended to conform to applicable laws so as to be
valid and enforceable; or if it cannot be so amended without materially altering
the intention of the parties, it shall be stricken, and the remainder of this
Agreement shall remain in full force and effect.

18. Notices. Any notices, statements, payments, or reports required by this
Agreement shall be considered given if sent by United States Certified Mail,
postage prepaid and addressed as follows:

         If to CANCER CENTER:

                  Michael J. Best
                  Chief Financial Officer
                  The University of Texas M.D. Anderson Cancer Center
                  1515 Holcombe Blvd.
                  Houston, Texas  77030

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.

                                       -4-
<PAGE>   5
         If to SPONSOR:

                  David Nance
                  Managing Partner
                  Texas Biomedical Development Partners
                  100 Congress Avenue, Suite 200
                  Austin, Texas  78701

19. Captions. The captions in this Agreement are for convenience only and shall
not be considered a part of or affect the construction or interpretation of any
provision of this Agreement.

20. Governing Law. This Agreement shall be governed and interpreted in
accordance with the substantive laws of the State of Texas and with applicable
laws of the United States of America.

                                       -5-
<PAGE>   6
         IN WITNESS WHEREOF, CANCER CENTER and SPONSOR entered into this
Agreement effective as of the date first hereinabove written and have executed
three (3) originals each of which are of equal dignity.

TEXAS BIOMEDICAL DEVELOPMENT           THE UNIVERSITY OF TEXAS
PARTNERS                               M.D. ANDERSON CANCER CENTER

By:  /s/ DAVID NANCE                   By  /s/ MICHAEL J. BEST
   -------------------------------       ---------------------------------
         David Nance                            Michael J. Best
         Managing Partner                       Chief Financial Officer

I have read this agreement
and understand my
obligations hereunder:                 CONTENT APPROVED:

By:  /s/ JACK A. ROTH                  By:  /s/ DONNA S. GILBERG
   -------------------------------       ---------------------------------
         Jack A. Roth, M.D.                     Donna S. Gilberg, CPA
         Principal Investigator                 Manager, Sponsored Agreements

                                       FORM APPROVED:

By:  /s/ CHARLES M. BALCH              By:  /s/ MATTHEW E. BURR
   -------------------------------       ---------------------------------
         Charles M. Balch, M.D.                 Matthew E. Burr, J.D.
         Head, Division of Surgery              Legal Services Officer

                                       -6-
<PAGE>   7
                               BUDGET FOR PROTOCOL

                                      [ * ]

          [*] Certain information on this page has been omitted and filed
              separately with the Commission. Confidential treatment has been
              requested with respect to the omitted portions.

                                       -7-
<PAGE>   8
                                 AMENDMENT NO. 1

                                       TO

                               RESEARCH AGREEMENT

         This Amendment No. 1 to Research Agreement ("AMENDMENT") is made and
entered into as of July 20, 1994 by and between INTRON THERAPEUTICS, INC., a
Delaware Corporation ("SPONSOR") and THE UNIVERSITY OF TEXAS M.D. ANDERSON
CANCER CENTER ("CANCER CENTER"), a component institution of the University of
Texas System ("SYSTEM").

                                    RECITALS

1. SPONSOR and CANCER CENTER entered into a SPONSORED RESEARCH AGREEMENT FOR
CLINICAL STUDY, number CS 93-27, dated as of February 11, 1993 (the "RESEARCH
AGREEMENT').

2. SPONSOR, CANCER CENTER and the Regents of the University of Texas System have
entered into a PATENT AND TECHNOLOGY LICENSE AGREEMENT dated as of July 20, 1994
(the "LICENSE AGREEMENT").

3. CANCER CENTER and SPONSOR wish to extend the term of the RESEARCH AGREEMENT,
acknowledge that the RESEARCH to be conducted thereunder will include matters
beyond the clinical trial protocol attached to the RESEARCH AGREEMENT as
originally executed, and that SPONSOR will have the option to include within the
LICENSED SUBJECT MATTER under the LICENSE AGREEMENT any intellectual property
that is made in the course of performing under the RESEARCH.

         NOW, THEREFORE, it is hereby agreed as follows:

         a. DEFINITIONS. Any capitalized terms that are not otherwise defined
herein shall be as in the RESEARCH AGREEMENT or the LICENSE AGREEMENT. In
addition, for all purposes of this AGREEMENT, the term "RESEARCH" shall be
deemed to include all work of CANCER CENTER personnel in performing the clinical
trial described int he protocol attached as Exhibit 1 and as modified from time
to time, as well as any work that is performed by Dr. Jack A. Roth or other
CANCER CENTER personnel comprising additional research projects described in
Attachment A-n, where n represents the ordinal number of a particular project.

         b. Invention and Patents. Section 3 of the RESEARCH AGREEMENT shall be
amended as follows:

                  1. So much of Section 3(a) of the RESEARCH AGREEMENT as reads
"(i) arises out of work performed pursuant to the obligations of this AGREEMENT'
is hereby amended to read "(i) arises out of the Research;".

                  2. Paragraph (b) of Section 3 is hereby deleted and replaced
in its entirety with the following:
<PAGE>   9
                  "b.      In the event that an Invention is made, CANCER CENTER
                           shall notify SPONSOR, which notice shall reference
                           this Section 3 and include a description of the
                           Invention in reasonable detail. SPONSOR shall have
                           the-option to include all worldwide patent rights
                           with respect to such Invention within the "EXISTING
                           PATENT RIGHTS" under Section 2.3(a) of the LICENSE
                           AGREEMENT," and to include related information,
                           know-how, biological materials and the like within
                           the TECHNOLOGY RIGHTS under the LICENSE AGREEMENT. To
                           exercise such option with respect to any particular
                           Invention, SPONSOR shall so notify CANCER CENTER
                           within 120 days after receipt of CANCER CENTER's
                           notice thereof as described above. Promptly following
                           such exercise, the parties shall revise Schedule A to
                           the LICENSE AGREEMENT to reflect the additional
                           patent applications so included. CANCER CENTER
                           warrants to SPONSOR that CANCER CENTER has the right
                           to grant to SPONSOR the option and rights
                           contemplated in this Section 3 and that upon exercise
                           of the option described herein with respect to any
                           Invention, all worldwide patent rights therein will
                           be included under the LICENSE AGREEMENT."

         c. Term. Section 14 of the RESEARCH AGREEMENT is hereby amended by
adding to the end thereof the following: "Following such initial Eighteen (18)
month period, unless earlier terminated as provided in Section 15, this
Agreement shall continue in full force and effect until terminated by either
party for any reason on ninety (90) days prior written notice to the other
party."

         d. Other. Except as expressly provided in this AMENDMENT, all other
terms, conditions and provisions of the RESEARCH AGREEMENT shall continue in
effect as provided therein.

         IN WITNESS WHEREOF, CANCER CENTER and SPONSOR entered into this
AMENDMENT effective as of the date first hereinabove written and have executed
three (3) originals each of which are of equal dignity.

                                       -2-
<PAGE>   10
         IN WITNESS WHEREOF, each of the parties has executed this Amendment as
of the date first above written.

TEXAS BIOMEDICAL DEVELOPMENT           THE UNIVERSITY OF TEXAS
PARTNERS                               M.D. ANDERSON CANCER CENTER

By:  /s/ DAVID NANCE                   By  /s/ MICHAEL J. BEST
   -------------------------------       ---------------------------------
         David Nance                            Michael J. Best
         Managing Partner                       Chief Financial Officer

I have read this agreement
and understand my
obligations hereunder:                 CONTENT APPROVED:

By:  /s/ JACK A. ROTH                  By:  /s/ DONNA S. GILBERG
   -------------------------------       ---------------------------------
         Jack A. Roth, M.D.                     Donna S. Gilberg, CPA
         Principal Investigator                 Manager, Sponsored Agreements

                                       FORM APPROVED:

By:  /s/ HELMUTH GOEPFERT              By:      Not applicable
   -------------------------------       ---------------------------------
         Helmuth Goepfert, M.D.                 Matthew E. Burr, J.D.
         Head, Division of Surgery and          Legal Services Officer
         Anesthesiology (Ad interim)

                                       -3-
<PAGE>   11
                                    EXHIBIT 1

                                    PROTOCOL

                                       -4-
<PAGE>   12
                                 AMENDMENT NO. 2

                                       TO

                            CLINICAL STUDY AGREEMENT

STATE OF TEXAS
COUNTY OF HARRIS

         AMENDMENT, effective this 1st day of January, 1995, between THE
UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTER (hereinafter referred to
as"CANCER CENTER"), a component of THE UNIVERSITY OF TEXAS SYSTEM (hereinafter
referred to as "SYSTEM") located at Houston, Texas, and INTROGEN THERAPEUTICS,
formerly Intron Therapeutics, Inc. (hereinafter referred to as "SPONSOR"), of
the Clinical Study Agreement made by these parties and dated the 11th day of
February, 1993 and amended the 20th day of July, 1994, regarding research on the
evaluation and study of the "Clinical Protocol for Modification of Tumor
Supressor Gene Expression in Non-Small Cell Lung Cancer with a Retroviral Vector
Expressing Wildtype (normal) p53).

1. CANCER CENTER and SPONSOR agree that the period of work identified in the
original Clinical Study Agreement shall be extended to the later of February 29,
1996 or the completion of the project.

2. CANCER CENTER and SPONSOR agree that the work to be done during this extended
work period will be performed according to the procedures described in the
revised workscope, the title of which is "Clinical Protocol for Modification of
Tumor Supressor Gene Expression in Non-Small Cell Lung Cancer with a Retroviral
Vector Expressing Wildtype (normal) p53", a copy of which is attached hereto as
Exhibit I and incorporated herein by reference. The workscope has been amended
and approved in accordance with institutional policy. The Clinical Study
Agreement may be extended by the SPONSOR upon notification to CANCER CENTER and
Investigator to provide CANCER CENTER and Investigator with the funds needed to
complete the research provided the research is within the workscope as herein
described.

3. CANCER CENTER and SPONSOR agree that the specific additional costs associated
with this work [ * ].

4. SPONSOR and CANCER CENTER agree that payment of amounts by SPONSOR shall be
made [ * ].

         OTHERWISE, the terms and provisions of the original Agreement executed
on the 11th day of February, 1993 and amended on the 20th day of July, 1994 by
and between the parties hereto shall remain in full force and effect, provided,
however, that in the event of a conflict in the terms and conditions between
this Amendment No. 2 and the Clinical Study Agreement, the terms and conditions
of this Amendment shall prevail.

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.
<PAGE>   13
         IN WITNESS WHEREOF, the parties have executed two (2) original
counterparts of this Amendment No. 2, each of which are of equal dignity and
effective as of the date first hereinabove written.

INTROGEN THERAPEUTICS                  THE UNIVERSITY OF TEXAS
                                       M.D. ANDERSON CANCER CENTER

By:  /s/ DAVID NANCE                   By  /s/ DONNA S. GILBERG
   -------------------------------       ----------------------------------
         David Nance                            Donna S. Gilberg, CPA
         President                              Manager, Sponsored Programs

Date:    6/24/95                       Date:  6/22/95
     -----------------------------          -------------------------------

                                       I have read this agreement and
                                       understand my obligations hereunder:

                                       By:  /s/ JACK A. ROTH
                                         ----------------------------------
                                                Jack A. Roth, M.D.
                                                Principal Investigator

                                       By:  /s/ HELMUTH GOEPFERT
                                         ----------------------------------
                                                Helmuth Goepfert, M.D.
                                                Ad Interim Head, Div. of Surgery

Payment Mailing Address:

The University of Texas
M.D. Anderson Cancer Center
Attn.:  Manager, Sponsored Programs
P.O. Box 297402
Houston, Texas  77297
Tax ID:  74-6001118-A1

                                       -2-
<PAGE>   14
                                    EXHIBIT 2

                                     BUDGET

                                      [ * ]

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.

                                       -3-
<PAGE>   15
                                 AMENDMENT NO. 3

                                       TO

                            CLINICAL STUDY AGREEMENT

         AMENDMENT, effective this 31st day of December, 1995, between THE
UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTER (hereinafter referred to as
"CANCER CENTER"), a component of THE UNIVERSITY OF TEXAS SYSTEM (hereinafter
referred to as "SYSTEM") located at Houston, Texas, and INTROGEN THERAPEUTICS
(hereinafter referred to as "SPONSOR"), of the Sponsored Research Agreement made
by these parties and dated the 11th day of February, 1993 and subsequently
amended, regarding research on the evaluation and study of the tumor suppressor
gene expression in non-small cell lung cancer.

1. CANCER CENTER and SPONSOR agree that the period of work identified in the
original Clinical Study Agreement shall be extended to December 31, 1996.
Thereafter, this Agreement can be extended for additional annual periods upon
the mutual written consent of CANCER CENTER and SPONSOR.

2. CANCER CENTER and SPONSOR agree that the work to be done during this extended
work period will be performed according to the procedures described in the
additional Protocol, the title of which is "Modification of Tumor Suppressor
Gene Expression and Induction of Apoptosis in Non-Small Cell Lung Cancer (NSCLC)
with an Adenovirus Vector Expressing Wildtype p53 and Cisplatin," a copy of
which is attached hereto as Exhibit I and incorporated herein by reference. The
Protocol has been approved in Accordance with institutional policy.

3. Award. During the term of this Amendment as set forth herein and in
consideration for CANCER CENTER's performance of the Protocol, SPONSOR agrees to
pay CANCER CENTER a fee [ * ].

4. ACCESS TO INFORMATION. All results of and information arising from the
Research shall be made available and accessible to SPONSOR by CANCER CENTER.
SPONSOR shall have the right to obtain copies or duplicates of such results and
information on a timely basis, in either written or electronic form, upon
SPONSOR giving CANCER CENTER reasonable notice of SPONSOR's desire to obtain
such results and information.

         OTHERWISE the terms and provisions of the original Agreement executed
on the 11th day of February, 1993 and subsequently amended by and between the
parties hereto shall remain in full force and effect, provided, however, that in
the event of a conflict in the terms and conditions between this Amendment No. 3
and the Clinical Study Agreement, the terms and conditions of this Amendment
shall prevail.

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.
<PAGE>   16
         IN WITNESS WHEREOF, the parties have executed two (2) original
counterparts of this Amendment No. 3, each of which are of equal dignity and
effective as of the date first hereinabove written.

INTROGEN THERAPEUTICS                  THE UNIVERSITY OF TEXAS
                                       M.D. ANDERSON CANCER CENTER

By:  /s/ DAVID NANCE                   By  /s/ DONNA S. GILBERG
   -------------------------------       ----------------------------------
         David Nance                            Donna S. Gilberg, CPA
         President                              Manager, Sponsored Programs

Date:    6/22/95                       Date:  6/22/95
     -----------------------------          -------------------------------

                                       I have read this agreement and
                                       understand my obligations hereunder:

                                       By:  /s/ JACK A. ROTH
                                         ----------------------------------
                                                Jack A. Roth, M.D.
                                                Principal Investigator

                                       By:  /s/ HELMUTH GOEPFERT
                                         ----------------------------------
                                                Helmuth Goepfert, M.D.
                                                Ad Interim Head, Div. of Surgery

Payment Mailing Address:

The University of Texas
M.D. Anderson Cancer Center
Attn.:  Manager, Sponsored Programs
P.O. Box 297402
Houston, Texas  77297
Tax ID:  74-6001118-A1

                                       -2-
<PAGE>   17
                                    PROTOCOL

                                      [ * ]

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.

                                       -3-

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