experimental immunotherapeutic agents. Examples include lymphokine activated 
killer cells (LAK therapy), tumor infiltrating lymphocytes (TIL therapy), and 
autologous lymphocyte transfusion (ALT therapy) which employ stimulator renal 
tumor cells harvested at surgery. 2 Nephrectomy has also been used in Stage 
III T4b and Stage IV patients to decrease tumor burden prior to new 
experimental schedules of IL-2 therapy. 19 
2.2 RATIONALE FOR CELL BASED IMMUNOTHERAPY FOR METASTATIC RENAL CELL 
CARCINOMA: PRECLINICAL DATA WITH MFG RETROVIRAL VECTOR 
The transcendent rationale for tumor vaccine based immunotherapy of 
established cancer depends on the existence of tumor antigens capable of being 
recognized as foreign by the host immune system. The word "vaccine" is used 
in this context as the antigen source for activation of immune responses 
against established metastatic cancer, as opposed to prophylactic 
immunization. Recent evidence from a number of studies suggests that human 
cytotoxic T lymphocytes can recognize tumor-specific peptide antigens that 
arise either as a consequence of genetic alterations in human tumors, or 
induction in tumors of genes not expressed in normal adult tissues. The first 
human tumor— specif ic antigen recognized by human T cells was recently reported 
by Boon and colleagues, who identified a human melanoma specific antigen 
termed MAGE l. 30 
Active Immunotherapy of Cancer 
Active immunotherapy involves the injection of autologous tumor cells to 
generate either a novel or an enhanced systemic immune response which will 
result in the eradication of metastatic sites. The reinjected tumor cells are 
generally altered in some way - by coinjection of adjuvants, by uv- 
irradiation, or by genetic manipulation - in an attempt to enhance their 
immunogenicity . Tumor vaccines have been used previously to treat patients 
with various solid tumors including RCC. 30-45 Most studies have not compared 
vaccination strategies rigorously; unclear is which experimental variables 
exert significant effects on the resulting immune response. In the case of 
RCC, McCune and colleagues treated patients with irradiated tumor vaccines 
prepared immediately after surgery and administered weekly as intradermal 
injections. These cells were not expanded in primary culture. Doses ranged 
from 2.0 to 90 xlO 6 cells. 37 Eight of 16 patients, initially unreactive to a 
skin test with irradiated autologous tumor cells, converted to a positive 
delayed type hypersensitivity (DTH) reaction after therapy. Half of the DTH 
positive patients demonstrated prolonged survival associated with partial 
clinical responses. 37 No responses were observed if the DTH remained 
negative. 37 A significant advantage of "tumor vaccination" as active 
immunotherapy is that it is not reported to produce significant systemic 
toxicities, and can be delivered to outpatients. The most common toxicities 
reported previously are erythema, local pain, fever, and skin ulceration at 
the site of injection that generally resolve without intensive skin care in 1- 
3 weeks. More severe local reactions are related to the use of immune 
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