Increased immunogenicity of a spontaneous variant clone of the 13762A rat mammary adenocarcinoma

The 13762A rat mammary adenocarcinoma is weakly immunogenic and spontaneously metastasizes to regional lymph nodes and lungs. A clone (18A) was isolated from the parental tumor, which grew for 3 weeks in normal F344 rats, forming tumors up to 2-3 cm and some nodal metastases, and then completely regressed. Pretreatment of recipient rats with 450 rad permitted progressive growth and death due to metastases. The behavior of 18A has been stable during a period of 120 days in continuous culture or for 6 in vivo passages in irradiated rats. Regression of 18A was associated with intense tumor mononuclear leukocytic infiltration, whereas parental tumors of the same size recruited few leukocytes. Regressions occurred when 18A cells were placed intradermally, sc, or im, but iv injections were not rejected. Parental tumors grew progressively at all sites. Regressor rats were specifically immune to challenge with both 18A and parental tumor but not to an unrelated mammary carcinoma (R3230AC). Irradiated 18A tumor cell vaccines protected recipients against challenge with parental tumor, but similar vaccines of irradiated parental tumor cells were ineffective. The systemic adoptive transfer of immune lymphocytes more strongly inhibited the growth of established (7 days) 18A than parental tumor. It was concluded that the parental 13762A tumor contained stable variants that were significantly more immunogenic and more susceptible to immune attack than the parental tumor. Such variant tumor lines may be useful in the study of the host response to metastasis.