Combination treatment with irritant and recombinant interleukin 2 in the peritoneal cavity for evoking effective anti-tumor activity: generation of lymphokine-activated killer cells and tumor-specific killer cells.
Meth A sarcoma, growing in the subcutaneous tissue of syngeneic BALB/c mice, regressed completely after an intraperitoneal (ip) injection of proteose peptone (PP) (on day 6) followed by 2 ip administrations (on days 7 and 8) of human recombinant interleukin-2 (IL-2, 25 micrograms/day), whereas one such treatment alone had little effect on the tumor growth. While this combination treatment was effective in anti-asialo GM1 antibody-treated mice, no such effect was noted in T cell-depleted ATXFL (thymectomized, irradiated and fetal liver cell-reconstituted) mice. These results show that T cells are mainly responsible for this antitumor effect. Treatment with a combination of PP and IL-2, but not with either PP or IL-2 alone, resulted in a marked increase in the T cell population in the peritoneal cavity after the treatment. At an early stage after the combination treatment, both peritoneal exudate cells (PEC) and spleen cells exhibited killing activity with a promiscuous specificity. However, at a later stage, 7 days after the treatment, Meth A-specific killer activity was observed in both PEC and the spleen. Meth A rechallenge was rejected by the mice in which the tumor had regressed, but the antigenically different Meth 1 was accepted by them. A similar result was obtained in Winn's neutralization test. These results suggest that this combination treatment, which is effective in the generation of lymphokine-activated killer cells in the peritoneal cavity, finally resulted in the induction of tumor-specific killer cells in the periphery. These results clearly show the anti-tumor efficacy of combination treatment with PP and rIL-2.
Uchida
H
H
Department of Immunology, Kyushu University, Fukuoka.
Taniguchi
K
K
Nomoto
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002364:Caseins / Q000627:therapeutic use*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D004359:Drug Therapy, Combination; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000627:therapeutic use*; D010529:Peritoneal Cavity / Q000166:cytology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy
D000276:Adjuvants, Immunologic; D002364:Caseins; D007376:Interleukin-2; D010446:Peptide Fragments; D011994:Recombinant Proteins; C018135:proteose-peptone; D008748:Methylcholanthrene