Significance of arming, potentiating and blocking factors as correlates of tumour-host interaction in the hamster SV40 system

Abstract

The study of blocking factors requires in vitro assay of cell mediated immunity that parallels the in vivo response. By microcytotoxicity testing, progressor and immune peripheral blood lymphocytes caused significant target cell reduction. The cytotoxicity was specific as no cytotoxic effect was detected against unrelated normal as well as a malignant target cell lines. No anti-tumour effect was noted when progressor peripheral blood lymphocytes were evaluated in the Winn assay. In marked contrast, immune peripheral blood lymphocytes were capable of preventing tumour growth in the Winn assay. Furthermore, hamsters repeatedly immunized with irradiated SV40 tumour cells could resist a live cell challenge. Thus immune peripheral blood lymphocytes were chosen as the effector population to evaluate the abrogation ability of serum in the microcytotoxicity assay.

Serum from hamsters with progressively growing SV40 tumours did not block, neutralize or potentiate in vitro lymphocytotoxicity. However, serum taken from hamsters before the appearance of a palpable tumour, potentiated in vitro lymphocytoxicity. Serum taken from hamsters hyperimmunized with irradiated SV40 tumour cells, live SV40 virus or following complete excision of a growing SV40 tumour armed normal effector cells and potentiated immune effector cells resulting in enhanced target cell destruction. Serum alone was not cytotoxic, suggesting a serum dependent cellular cytotoxicity effect.

Serum from hamsters in which tumours recurred after excision was capable of abrogating in vitro lymphocytoxicity. However, no antibody activity was detectable to cell surface antigens by the mixed haemadsorption test in the sera that demonstrated blocking or potentiating activity. Progressor serum was unable to enhance the growth of SV40 tumour cells in vivo.

The potentiating and arming activity of serum in this study directly parallels the cytostatic antibody activity described by Coggin et al. in the hamster SV40 system. Both cytostatic antibody activity and enhancement of in vitro lymphocytotoxicity activity correlates with in vivo tumour resistance. These results suggest that progressive primary tumour growth in this system may correlate with a lack of serum dependent cellular cytotoxicity rather than blocking factors, while the latter may be associated with recurrent and/or metastatic disease.