Induction of antitumor L3T4-positive T cells by OK-432 at tumor sites in mice.
We have previously reported the development of antitumor effector cells by day 12 after tumor implantation using a murine malignant ascites model with BAMC-1 tumor, which could be cured completely by five consecutive i.p. injections of OK-432 starting on day 2. In contrast, the OK-432 treatment with the same protocol failed to cure the tumor-bearing athymic mice, though it could suppress tumor growth temporarily. The results suggest that T cells may play a critical role in achieving a therapeutic effect. The present study was designed to clarify the nature of the antitumor effector cells induced by OK-432 in euthymic mice. The number of tumor cells in the peritoneal cavity of OK-432-treated euthymic mice increased gradually up to day 12 and dropped suddenly on day 14, while in the athymic mice the tumor cells transiently decreased in the first 7 days then started to expand drastically on day 8. The timing of the appearance of the effector cells was examined by adoptive-transfer experiments. The peritoneal exudate cells (PEC) obtained from BAMC-1 bearing euthymic mice on various days during the treatments with OK-432 were passively transferred intraperitoneally on the respective days (synchronous transfer) or on day 7 (convergent transfer) to BAMC-1-bearing athymic mice, which were treated similarly with OK-432. More than 85% of the recipient athymic mice survived when an adoptive transfer was made on and after day 7. These results indicated that the effector cells developed before day 8 in euthymic mice. The effector cells detectable on day 7 in the PEC represent plastic- or nylon-wool-column-nonadherent cells, which could cure the tumor-bearing athymic mice. Furthermore, the effector cells were destroyed when the nylon-wool-column-nonadherent cells were treated with an anti-L3T4 antibody and complement whereas the same treatment with anti-Lyt2 antibody had no effect. These L3T4+ cells did not possess asialo-GM1 antigen. Although the exact mechanism of action of the effector cells is yet to be clarified, the induction of human equivalents of this type of effector cell would be a good parameter indicative of clinical effects induced by OK-432 or other biological response modifiers in an individual cancer patient.
Moriya
Y
Y
Central Research Laboratories, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Sato
H
H
Ito
K
K
Saito
M
M
Yoshida
T
T
Ishida
N
N
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001201:Ascites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000032:analysis; D007116:Immunization, Passive; D016130:Immunophenotyping; D007167:Immunotherapy; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000628:therapy*; D010529:Peritoneal Cavity / Q000166:cytology; D010844:Picibanil / Q000008:administration & dosage*; D016019:Survival Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D005677:G(M1) Ganglioside; D010844:Picibanil; C018835:asialo GM1 ganglioside