Interleukin-2 gene-modified allogeneic melanoma cell vaccines can induce cross-protection against syngeneic tumors in mice.
Vaccination using well-characterized allogeneic tumor cell lines expressing standardized doses of immunostimulatory cytokines is an attractive alternative for autologous gene-transfected tumor cell vaccines. In the present study, we show that vaccination with irradiated allogeneic K1 735 (H-2k) or B16F10 (H-2b) melanoma cells induces a moderate degree of cross-protection against the M-3 melanoma (H-2d) in DBA/2 mice. Cross-protection against the syngeneic tumor was markedly improved when the allogeneic vaccines were transfected with the interleukin-2 (IL-2) gene. The IL-2 gene-modified allogeneic vaccines were effective for prophylactic vaccination against subsequent tumor challenge and for therapeutic vaccination against pre-existing tumor deposits, with efficacies that were comparable with that of the IL-2 gene-modified syngeneic vaccines. Cross-protection correlated with the cytotoxic activity of splenocytes against M-3 targets. Allogeneic vaccination was not effective in another model, against the B16F10 melanoma in C57BL/6 mice, irrespective of genetic modification with the IL-2 or granulocyte-macrophage colony-stimulating factor genes.
Kircheis
R
R
Department of Cancer Vaccines, Boehringer Ingelheim Austria, Vienna. ralf.kircheis@vie.boehringer-ingelheim.com
Küpcü
Z
Z
Wallner
G
G
Rössler
V
V
Schweighoffer
T
T
Wagner
E
E
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000473:pathology; D016019:Survival Analysis; D014161:Transduction, Genetic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured / Q000528:radiation effects / Q000637:transplantation; D014611:Vaccination
D019496:Cancer Vaccines; D007376:Interleukin-2