B30-MDP, a synthetic muramyl dipeptide derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice.
The effect of a muramyl dipeptide derivative (B30-MDP) on the augmentation of antitumour immunity against highly metastatic L5178Y-ML25 mouse lymphoma cells was examined in CDF1 (Balb/c x DBA/2) mice. Mice immunized with a mixture of X-irradiated tumour cells (10(3)) and B30-MDP (100 micrograms) on 7 days prior to challenge by viable tumour cells displayed a significant decrease in metastasis towards the target organs, liver and spleen, compared with that of untreated mice. Immunization of mice with the mixture on day 5 or 7 after tumour challenge, when the level of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in sera of mice inoculated with viable tumour cells was observed to be normal, caused less metastasis than immunization with X-irradiated tumour cells alone. Sensitization with X-irradiated tumour cells admixed with B30-MDP induced almost two times higher cytotoxicity of spleen cells against L5178Y-ML25 lymphoma cells than sensitization with X-irradiated tumour cells without B30-MDP. In contrast, cytotoxic activity of spleen cells against another target, L1210 lymphoma cells derived from BDF1 mice, was not observed by immunization with X-irradiated L5178Y-ML25 cells with or without B30-MDP. Specific lysis by splenic cells of the immunized mice against L5178Y-ML25 cells decreased to the normal level when T cells were deleted from the immunized spleen cells by the treatment of rabbit anti-mouse Thy1.2 antibody and rabbit complement. These results indicate that B30-MDP is able to augment a specific tumour immunity due to the enhancement of cytotoxicity mediated by T lymphocytes, and is useful as an immunopotentiating agent for active immunization of inactivated tumour cells.
Yoo
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YC
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saiki
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Sato
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Azuma
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D007940:Leukemia L5178 / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D013154:Spleen; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D014614:Vaccines, Synthetic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C044706:B 30-muramyl dipeptide