Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): I--Utilization of cimetidine and cyclosporine A.

Cimetidine (CMT), cyclosporine A (CsA), interleukin 2 (IL 2), were used to characterize the anticancerous effect of a polyantigenic immunodulator (PAI). PAI consists of a mixture of inactivated bacteria and influenza virus in a peanut oil-arlacel A-aluminum monoesterate emulsion. Antitumoral activity was tested on Ehrlich's ascites tumor (EAT) implanted into Swiss-Webster (allogeneic) or C57BL/6J (syngeneic) mice. PAI antitumor activity was enhanced by CMT acting synergistically by reducing substantially the tumor growth and increasing the percentage of surviving mice, while CsA suppressed this activity. PAI or its individual components were able to induce significant lymphocyte blastogenesis in mouse (C57BL/6J)-spleen lymphocytes and IL-2 enhanced considerably this lymphoproliferative response. The results suggest that PAI acts at the level of cellular immunity.

Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): II--Involvement of NK cells and adoptive immunotherapy.

Natural killer (NK) cell activity and adoptive immunotherapy were used to characterize the anticancerous effect of a polyantigenic immunomodulator (PAI). PAI consists of a mixture of inactivated bacteria and influenza virus in a peanut oil-arlacel A-aluminum monoesterate emulsion, shown previously to have antitumoral activity in mice implanted with Ehrlich's ascites tumor. The administration of PAI, its bacterial or viral component strongly increased the in vitro activity of NK cells of splenocyte populations obtained from Swiss-Webster (allogeneic) and C57BL/6J (syngeneic) mice, specially during the early post-induction period. On the other hand, PAI-sensitized, allogeneic or syngeneic lymphocytes were transferred successfully to tumor-bearing mice implanted with Ehrlich's ascites tumor, reducing tumor growth and increasing survival. The results confirm our previous suggestions that PAI acts probably at the level of cellular immunity. Therefore complex polyantigenic substances such as PAI could be used directly alone, in combination with other immunoadjuvants or to sensitize in a global manner immunocompetent cells to be employed in adoptive immunotherapy.