Evaluation of the Cellular and Humoral Immune Response of the Hamster to Simian Virus 40 Tumors

Abstract

<p>The SV40 virus system has been extensively investigated as a model for the study of antigens and immune responses to such antigens associated with oncogenesis. While there is considerable data available on the nature of resistance to autochthonous and transplantable tumors in this system, there is very little information on the mechanisms of progressive tumor growth. To evaluate the role of serum factors on progressive tumor growth, an in vitro assay of cell-mediated cytotoxicity using peripheral blood lymphocytes as effector cells and a transplantable SV40 induced tumor (HSO) as the target cell was adapted to the hamster SV40 system. Progressor, immune and post-excision peripheral blood lymphocytes caused a significant reduction in the number of target cells as compared to normal peripheral blood lymphocytes. The cytotoxicity was specific as there was no significant difference between the cytotoxic effect of 'immune' and normal effector cells when tested against unrelated normal and malignant target cell lines. In marked contrast, the cytotoxicity demonstrated by peritoneal exudate cells was non-specific as significant cytotoxicity could be demonstrated on both related and unrelated malignant cell lines.</p> <p>Serum from hamsters with progressively growing tumors either transplantable (H50 cells) or autochthonous virus induced, did not block, neutralize or enhance in vitro lymphocytotoxicity. However, serum taken from hamsters prior to the appearance of a palpable tumor enhanced the cytotoxicity of immune lymphocytes. Serum from hamsters hyperimmunized with irradiated H50 cells, live SV40 virus, or following SV40 virus, or following complete excision of a growing tumor caused enhanced cytotoxicity of immune and normal lymphocytes. Serum alone was not cytotoxic suggesting an antibody dependent cellular cytotoxicity effect. Serum from hamsters in which tumors recurred after excision was capable of abrograting in vitro lymphocytotoxicity. The inability of progressor serum to enhance or abrograte in vitro lymphocytotoxicity cannot be explained on the basis of preferential absorption of these serum factors by an enlarging tumor mass as low pH tumor eluates could not enhance or abrograte in vitro lymphocytotoxicity.</p> <p>The activity of immune serum in this study directly parallels the cytostatic antibody activity described by Coggin et al in the hamster SV40 system. These results suggest that progressive primary tumor growth in this system may correlate with a lack of antibody dependent cellular cytotoxicity rather than blocking factors, while the latter may be associated with recurrent and/or metastatic disease.</p>