Late metastatic disease was studied in LIO tumor-bearing guinea pigs which had shown an initial therapeutic response to a vaccine of x-irradiated LIO 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 Ll O parent were designated LI O variant I (LI O-1) and LI O variant 2 (L10-2), respectively. Comparisons of the antigenic properties of the LIO parent and the two LIO variants showed that the earlier occurring metastasis (L10-1) was not distinguishable from the LIO 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 LlO-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 LIO tumor-bearing animals was successful under defined conditions of treatment.