grow in vitro with IL-2 but will show decreased in vivo efficacy if not re- 
exposed to tumor in culture (presumably due to the requirement of cultured T- 
cells for antigen exposure) (25 ) . Furthermore, irradiated or non-viable tumor 
and tumor extracts produce immune responses in animals that are typically 
inferior to the responses to viable tumor (26). Therefore the injection of 
small amounts of viable tumor at a cutaneous site might not only result in 
tumor for TIL production, but also generate an immune response superior to 
that demonstrated using irradiated or non-viable tumor. This immune response 
may not only be seen at the tumor site, but pre-clinical models show that T- 
cells can be recovered in lymph nodes draining the site of tumor inoculation, 
which can be expanded in culture and show in vivo anti-tumor activity. This 
aspect of the cellular immune response to tumor immunization will be discussed 
later in the protocol. 
Because tumor growth at the transplant site is necessary for TIL 
production, it is important to know if that will occur and what are the 
potential risks involved. Southam and Brunschwig inoculated a series of 
patients with a variety of metastatic cancers with their own resected tumors 
in graded doses (27,28). This revealed that the majority of patients could 
grow tumors at these inoculation sites if an adequate inoculum was 
administered. These were all patients with widely metastatic disease or 
unresectable advanced cancers and no impact from the inoculations on their 
overall clinical course was identified. For patients with widely metastatic 
cancer, a very small local cutaneous tumor inoculation (representing a 
fraction of their progressive metastatic disease) and subsequent resection of 
any growing tumor, is unlikely to significantly accelerate the course of their 
systemic disease. In support of this, one can cite the extreme case of tumor 
auto-inoculation which occurs when large numbers of malignant cells are 
intravenously infused as a result of peritoneal-vdnous shunting to palliate 
malignant ascites. Multiple clinical and post-mortem studies fail to show 
significant decreases in survival or alterations in the pattern of metastatic 
disease in shunted versus non-shunted patients (29-31\. Such shunted patients 
Recombinant DNA Research, Volume 15 
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