Experimental cancer immunotherapy: modification of tumor cells to increase immunogenicity

Abstract

Firmly established transplantable C3H/HeJ mammary carcinomas can be inhibited by host challenge with Vibrio cholerae neuraminidase (VCN)-treated tumor cells. The effect is totally immunospecific, even VCN-treated tumors bearing shared mammary tumor virus (MTV) antigen cannot induce the regression. Thus, VCN is capable of increasing the immunogenicity of the private, unique-unshared tumor antigens on mammary carcinomas; VCN is incapable of increasing the immunogenicity of the shared MTV-associated tumor antigen even in syngeneic C3HeB/FeJ MTV-free mice. The immunoregressive effect of VCN-treated tumor cells can be augmented by subtotal or total surgical excision of large transplantable tumors. Spontaneous mammary tumors in retired breeder C3H/HeJ female mice can be made to regress by two immunological maneuvers: (1) repeated intratumor injections of VCN and/or BCG; and (2) total excision and immunotherapy with VCN-treated autochthonous mammary tumor cells. The use of VCN-treated transplantable mammary tumor cells sharing the MTV-associated antigen was not better than excision alone. The evidence supports the idea that active specific immunotherapy of spontaneous tumors with VCN-altered tumor cells may require the use of autochthonous cells.