Tumor-enhancing and tumor-inhibiting in vivo effects of phytohaemagglutinin : Study on proliferation of transplantable mouse melanoma

Abstract

Phytohaemagglutinin (PHA)-induced stimulation, as well as inhibition of tumor growth in mice transplanted with Harding-Passey melanoma, has been demonstrated in the present study. Tumor proliferation could be modulated depending upon the dose of PHA and its time of administration with respect to tumor implantation. Once a critical dose of PHA was exceeded or tumor implantation has been performed, a shift from tumor-enhancing to tumor-inhibiting activity took place. Furthermore, experimental conditions which enhanced tumor proliferation, increased the rate of “tumor takes” and vice versa. While the inhibitory effect of PHA was maintained in retransplanted tumors, PHA-induced enhancement of tumor growth was no longer observed during successive passages of the melanoma in untreated recipients. In addition, spleen cells of melanoma bearing mice were tested for their ability to respond to sheep red blood cells (SRBC). SRBC-specific responses decreased progressively during the course of tumor-bearing and additional treatment with PHA including tumor-enhancing treatment was associated with a further depression of splenic immunocompetence to this antigen. Our results, suggesting a dose and time dependent different action of PHA on tumor growth, indicate how critically experimental parameters must be controlled for applying immunotherapy with this mitogen.