observed after extended culture. Hence, all retroviral vector supernatants used to infect patient cells will 
be screened for replication competent virus by standard assays (14). It is theoretically possible for the 
retroviral vector to insert the transgene into a proto-oncogene or tumor suppressor gene resulting in 
cellular transformation by insertional mutagenesis. The likelihood of this occurring is extremely small. 
The neo*^ gene transferred into the genetically modified tumor cells inactivates neomycin and related 
antibiotics such as amikacin. As the genetically modified cells will be injected subcutaneously, local 
expression of the neo*^ gene is unlikely to effect treatment with these antibiotics at other sites. In 
addition, other more commonly used antibiotics such as gentamycin and tobramycin are not inactivated 
by the neo’^gene. Hence, the introduction of this gene into a local area of the patient is not expected to 
affect clinical management of infections. 
5.3 Treatment of Toxicity 
Local toxicity at the sites of cell administration will be treated with either topical steroids and/or surgical 
excision of the injection site as deemed appropriate. Hypersensitivity reactions may occur. Chills, fever 
and/or rash may be treated symptomatically with antipyretics and antihistamines. Patients should not be 
treated prophylactically. 
Should arthralgias, lymphadenopathy or renal dysfunction occur, the investigators should be notified and 
treatment with corticosteroids and/or antihistamines may be instituted. Anaphylactoid type 
hypersensitivity reactions are not anticipated. However, should anaphylaxis occur, administration of 
epinephrine, fluids, steroids and cardiopulmonary support should be instituted as needed. 
6.0 Treatment Plan 
6.1 Location 
Patients will be treated at Sharp Memorial Hospital, San Diego, CA. 
6.2 Administration of Biological Agents 
Patients will be randomly assigned to receive either autologous or allogeneic IL-2 transduced tumor cells. 
Subjects will receive at least three subcutaneous immunizations at least two weeks apart with one of the 
following preparations: 
1) Irradiated autologous tumor cells genetically modified to secrete IL-2. 
2) Irradiated allogeneic HLA- A2 positive GT9 tumor cells genetically modified to 
secrete IL-2. 
All subjects will be treated as outpatients. Vital signs will be checked prior to immunization. 
Subsequently, vital signs should be obtained qlh x 2. The patients should be examined qlh x 2 for 
inflammation at the injection site and for evidence of rash, wheezing or edema. Provided that there are 
no contraindications, subjects may be discharged 2 hours after drug administration. If discharge is 
contraindicated, patients will be followed in the hospital on a regular basis as deemed appropriate. 
7.0 Therapy Modification 
7.1 Dose Escalation 
We plan to initiate therapy with transduced cells that secrete 25 units of IL-2/24 hrs. This dose of IL-2. 
was well tolerated in our first patient and was the lowest dose associated with the generation of a cellular 
anti-tumor immune response. Our data indicate that the transduced cells will express approximatley 20 
Recombinant DNA Research, Volume 19 
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