Augmentation of tumor immunity in mice by intralesional injection of vitamin A.
We investigated the antitumor effect of vitamin A(VA) using the double grafted tumor technique to examine whether VA administered into a primary tumor (intralesionally or i.l.) accelerates antitumor immune reactions so that growth of the secondary tumor may be more effectively inhibited than by other systemic administration routes. In the double grafted tumor system, where BALB/c mice were inoculated with MethA fibrosarcoma cells into the right inguinal region (1 x 10[6] cells) on day 0 and later into the left (3 x 10[6] cells) on day 10, the injection of VA at a dose of 1000 IU/mouse i.l., s.c., i.p., and i.v. on days 3 through 7 inhibited the growth of the secondary tumor to the same extent, while VA at the i.l. dose of 100 IU/mouse into the primary tumor inhibited more effectively than by any other administration route. VA did not inhibit the secondary MethA growth in BALB/c (nu/nu) mice. The spleen cells taken from VA-treated tumor-bearing mice prevented the growth of MethA tumors in naive BALB/c mice when given as a mixture with the MethA inoculum (the Winn assay). The delayed-type hypersensitivity (DTH) response to methylated bovine serum albumin (MBSA) antigen was augmented when VA (1000 IU) was injected at the site of the antigen injection. These results suggest that the direct interaction of VA with the tumor cells may be necessary for the tumor immunity-potentiating effect of VA, and that T-lymphocyte-mediated tumor immunity is involved in the anti-tumor effect of VA. The antitumor mechanism of VA seems to involve retinoid receptors, because the benzoic acid derivative Am80, which has been reported to exert retinoidal activity by binding to specific retinoid receptors, also showed activity.
Kashida
T
T
Research Laboratories, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
Narasaki
N
N
Yano
T
T
Tsuzurahara
K
K
Takeyama
S
S
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007267:Injections; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D012710:Serum Albumin, Bovine / Q000276:immunology; D013154:Spleen / Q000201:enzymology; D014183:Transplantation, Heterologous; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*
D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D014801:Vitamin A; D012710:Serum Albumin, Bovine