Antigenic heterogeneity of the guinea pig line 10 hepatocarcinoma. Implications for active specific immunotherapy

Summary Late metastatic disease was studied in L10 tumor-bearing guinea pigs which had shown an initial therapeutic response to a vaccine of x-irradiated L10 tumor cells plus BCG. A single metastatic lesion was isolated from two different animals showing evidence of tumor recurrence on days 134 and 212 after tumor implantation. These putative variants of the L10 parent were designated L10 variant 1 (L10-1) and L10 variant 2 (L10-2), respectively. Comparisons of the antigenic properties of the L10 parent and the two L10 variants showed that the earlier occurring metastasis (L10-1) was not distinguishable from the L10 parent in the ability of the tumor cells to immunize normal animals and elicit delayed-type hypersensitivity (DTH) responses in immunized animals. In contrast, the later occurring metastasis (L10-2) showed a decrease in antigen expression compared with the L10-parent. Although it has been postulated that the antigenic heterogenity of primary or early-passage tumors is lost upon repeated in vivo passage, the present studies show that such heterogeneity does exist or can be induced in a transplantable guinea pig tumor of long duration. Despite the presence of antigenic heterogeneity, active specific immunotherapy of L10 tumor-bearing animals was successful under defined conditions of treatment.