Properties of a herpesvirus-transformed hamster cell line: immunogenicity of sublines of high and low metastatic potential

Abstract

The immunogenicity of a herpesvirus hominis type-2-transformed hamster cell line (HSV-2-333-2-26) of low spontaneous metastatic ability was compared with that of its two in vivo-derived sublines of increased metastatic potential. The parent (HSV-2-333-2-26) tumour was immunogenic as assessed by protection against tumour challenge afforded by implantation of irradiated tumour cells or tissue. In contrast, the two metastatic sublines, designated Met A and Met B, were non-immunogenic as defined by the above critera . However, the parent Met A and Met B tumours were shown to possess a common antigen(s), since immunization with irradiated parent tumour cells afforded protection to challenge with Met A or Met B. Immunization with the metastatic sublines, however, gave no protection to homologous or heterologous tumour challenge. Bacillus Calmette-Guérin (BCG) inoculated in admixture with irradiated tumour cells and followed 7 days later by one immunization with X-irradiated tumour cells alone, increased host immunocompetence to subsequent homologous or cross-tumour cell challenge with parent, Met A or Met B cells. The immunity raised by using BCG plus irradiated tumour cells was shown to be specific to antigens expressed on the HSV-2 parent cell line and its metastatic sublines. In addition, BCG admixed with live inocula of parent, Met A or Met B cells induced contact suppression of in vivo tumour growth of the parent cells, but not of Met A or Met B cells. It is suggested from these studies that the parent tumour possesses a tumour-specific transplantation antigen(s) ( TSTAs ) which is not functionally active on its metastatically derived sublines. Common antigens, shared between the parent and Met A and Met B cells, are detectable by cross-challenge experiments, but they themselves appear not to be immunologically offensive. The loss of immunogenicity is discussed as a possible mechanism for the in vivo selection of sublines with increased metastatic potential.