GENERATION OF IMMUNOPROTECTION AGAINST SQUAMOUS-CELL CARCINOMAS BY IN-VITRO CULTIVATION AND A POSSIBLE MECHANISM OF ACTION

The immunogenicity of individual diethylnitrosamine (DEN)-induced fore stomach carcinomas in female BALB/c mice was investigated following in vitro and in vivo cultivation. Of the five transplantable tumor lines studied, (DEN1, DEN3, DEN6, DEN8, and DEN9) only two (DEN6 and DEN8) showed some degree of immunogenicity. DEN1, DEN3, and DEN9 were highly tumorigenic with very little immunogenic potency as judged by tumor t ransplantation-excision assay, Winn neutralization, and antibody bindi ng tests. These three tumors grew rapidly and showed a high degree of malignancy. DEN1 and DEN3 also metastasized readily. Cell lines from D EN6 and DEN9 lost their tumorigenicity at the 5th and 50th passage of culture, respectively. Although DEN1 and DEN3 did not lose their tumor igenicity, the number of tumor cells required to produce tumors increa sed substantially and their ability to metastasize was lost. Tumor tra nsplantation studies, with these cultured cell lines in normal and x-i rradiated recipients, suggested that the decrease in tumorigenicity ma y be immunologically mediated. Mice immunized with the in vitro lines demonstrated transplantation resistance against the respective in vitr o and in vivo lines. The treatment of in vivo or in vitro propagated c ells with periodic acid or neuraminidase enhanced antigen-antibody bin ding significantly. The effect of these chemicals became less pronounc ed as in vitro culture continued. It appears that during in vivo culti vation the antigenic determinants are masked or modulated by some glyc oprotein or glycolipid molecules which render them non-, or very weakl y, immunogenic.