Markedly induced asialoGM1+CD8+ T cell production and enhancement of antimetastatic activity by interferon beta with folic or folinic acid.
Either folic or folinic acid enhanced the antimetastatic activity of recombinant murine interferon beta (rMulFN beta) toward highly metastatic colon carcinoma 26 (Co 26Lu). Folinic acid administered with rMuIFN beta markedly increased asialoGM1+CD4+ and asialoGM1+CD8+ T cell production in the peritoneal cavity but not in the thymus and spleen. Peritoneal cells expressed killing activity toward Co 26Lu cells in vitro. In athymic nude mice, the above combination produced many asialoGM1+CD4+ and few asialoGM1+CD8+ T cells in the peritoneal cavity, but did not decrease lung metastatic colonies. AsialoGM1+CD4+ T cells would thus appear to have no or only very weak killing activity toward these tumor cells. The antimetastatic activity of folinic acid with rMuIFN beta was significantly decreased with anti-asialoGM1 and anti-CD8 antibodies. Inactivated CD8+ and asialoGM1+ cells cease to have killing activity toward Co 26Lu cells as shown by Winn's assay. AsialoGM1+CD8+ cell production was markedly induced in the peritoneal cavity by treatment with rMuIFN beta and folinic acid. AsialoGM1+CD8+ T cells may be inhibiting lung metastasis of Co 26Lu. Folinic acid and interferon are used in combination therapy with 5-fluorouracil for biochemical modulation. Folinic acid with interferon, as adjuvant therapy, may promote the induction of CD8+ T cell production with consequent prevention of metastasis.
Iigo
M
M
Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Moriyama
M
M
Suzuki
I
I
Tsuda
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D005492:Folic Acid / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000378:metabolism*; D016899:Interferon-beta / Q000494:pharmacology*; D002955:Leucovorin / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010529:Peritoneal Cavity
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D016899:Interferon-beta; D005492:Folic Acid; D002955:Leucovorin