Survival of Fischer rats bearing 9L
gliosarcoma in the brain was measured to determine the efficacy of 1) systemically administered
chemotherapy with local adoptive immunotherapy (chemo-adoptive immunotherapy) or 2) systemically administered chemo-
immunotherapy. Winn assays, where
tumor instillation coincided with the start of treatment, and one-week established
tumor assays were conducted. Survival of chemo-adoptive immunotherapy treated groups given intraperitoneal
cyclophosphamide and intracranial lymphokine activated killer cells and recombinant
Interleukin-2 was significantly extended when compared to
sham treated control groups, to groups given
chemotherapy with intraperitoneal
cyclophosphamide, and to groups treated by local adoptive immunotherapy with intracranial lymphokine activated killer cells and
Interleukin-2. The killer cells were generated from spleens of donor rats that either had or had not been given
cyclophosphamide 24 h earlier. Long-term survivors (9/39), sacrificed at day 70, were obtained only in the chemo-adoptive immunotherapy treated groups; 7/39 had no histologic evidence of
tumor and had focal sterile
abscesses at the site of killer cell instillation. Average group weight plotted over time showed that there was acceptable toxicity with chemo-adoptive immunotherapy; the toxicity was identical to that obtained with systemic
cyclophosphamide treatment. In contrast, survival of chemo-
immunotherapy treated groups given systemic
cyclophosphamide and
Interleukin-2 was not significantly extended from groups which were
sham treated or treated only with systemic
Interleukin-2. Rapid decline of average group weight plotted over time and early deaths following chemo-
immunotherapy treatment indicated that the regimen was toxic. The effect of
cyclophosphamide administration on the splenocytes of donor rats and the LAK cells generated from them was determined by in vitro studies analyzing cell number, viability, phenotypic expression and cytotoxicity against 9L
tumor. In the treatment of this
intracranial neoplasm, the beneficial effects of
cyclophosphamide were determined to occur in situ in the
tumor-bearing host. No benefit resulted from
cyclophosphamide treatment of donor rats that supplied splenocytes for LAK cell production.