STRAIN DIFFERENCES IN THE ANTITUMOR ACTIVITY OF AN IMMUNOPOTENTIATOR, NOCARDIA RUBRA CELL-WALL SKELETON, IN B10 CONGENIC AND RECOMBINANT MICE

Abstract

An immunogenetic evaluation of the antitumor activity of the immunopotentiator Nocardia rubra cell-wall skeleton (N. rubra-CWS) has been performed using non-virus-producing tumors induced by the Schmidt-Ruppin strain of Rous sarcoma virus (RSV) in B10 congenic and recombinant mice. Live tumor cells mixed with either N. rubra-CWS or a placebo control were inoculated intradermally into the right flank of syngeneic mice. With N. rubra-CWS, the development and growth of B10 mouse tumors, S1018(B10) and B1OSA2F, in B10(H-2^b) mice were completely inhibited in all test mice. B10.A(5R) mouse tumor, S322(5R), was completely suppressed in 23 of 25 B10.A(5R)(H-2ⁱ⁵) mice, and B10.BR mouse tumor, S623(BR), was completely suppressed in 7 of 14 B10.BR(H-2^k) mice. However, B10.D2 mouse tumor, S908(D2), in B10.D2(H-2^d) mice and B10.A mouse tumors, S826(BA) and B10ABr1F, in B10.A(H-2^a) mice were not suppressed at all by N. rubra-CWS. N. rubra-CWS showed a remarkable antitumor effect in B10 mice, not only in mixed inoculation with the tumor cells but also with intratumoral administration. These effects were not seen in B10.A mice. Peritoneal exudate cells (PEC) from B10 and B10.A strains previously treated intraperitoneally with N. rubra-CWS and/or MMC-treated tumor cells showed cytolytic and cytostatic activities on tumor cells derived from both strains. These results did not reflect the strain difference seen in the in vivo studies. Mitogenic activity of N. rubra-CWS on spleen cells, however, was significantly different among B10 congenic mice; N. rubra-CWS induced greater blastogenesis of spleen cells from B10 mice than of those from B10.A mice, corresponding to the in vivo results showing strain difference. These results suggest that the host's immunogenetic background may play an important role in cancer therapy with immunopotentiators.