Showing papers by "Fred Hutchinson Cancer Research Center published in 1972"

Counteraction of the blocking of cell‐mediated tumor immunity by inoculation of unblocking sera and splenectomy: immunotherapeutic effects on primary polyoma tumors in rats

Abstract: Circulating lymphocytes of rats carrying progressively growing polyoma tumors are specifically cytotoxic to polyoma tumor cells in vitro. The serum of such rats can block this lymphocyte cytotoxicity, an effect probably mediated by tumor-specific antigen-antibody complexes. Inoculation of blocking serum into rats has previously been shown to facilitate tumor growth. It is now demonstrated that so-called “unblocking” antibodies can be produced by immunization of BCG primed rats or rabbits with tumor cells. These antibodies can counteract the effect of specific blocking sera and tumor eluate in vitro. When inoculated into rats which had previously received a polyoma tumor isograft, unblocking serum was found to inhibit the appearance of (or counteract) the blocking activity of serum in four of five rats. Tumors in these four rats grew progressively for 10-12 days and then completely regressed. The effects of inoculation of unblocking sera into rats carrying primary kidney sarcomas, and subjected to splenectomy, were studied by in vitro tests for blocking and unblocking activity and for homologous complement-dependent cytotoxicity on serially-drawn serum samples from all treated rats, as well as for cytotoxicity of circulating lymphocytes from some of the animals. The serum blocking activity decreased or disappeared in all rats treated with unblocking serum while animals inoculated in parallel with control serum showed no such alteration. While sera of untreated rats or rats inoculated with control serum never had any detectable homologous complement-dependent cytotoxic activity, such activity was demonstrated on several occasions in all tested rats inoculated with unblocking sera. Unblocking activity was observed in several of the treated animals. Inoculating of unblocking sera from either rats or rabbits in combination with splenectomy led to the disappearance of grossly visible tumor in two rats and to retardation of the tumor growth rate in seven of nine other rats. The survival time of nine of 11 rats treated with unblocking sera was significantly prolonged. These results show that immunotherapeutic effects can be achieved by serum treatment combined with splenectomy. Although other mechanisms have not been excluded, the “vertical” in vitro analysis of various facets of the anti-tumor immune status of these animals supports the hypothesis that procedures counteracting the blocking serum activity in vivo will allow the already present immune lymphocytes to exert their cytotoxic effect and thereby eliminate tumor cells.

Facilitation of polyoma tumor growth in rats by blocking sera and tumor eluate.

Abstract: It has been shown previously that sera of tumor-bearing individuals are capable of blocking specifically the lymphocyte cytotoxicity in vitro against the tumor cells in question. The present investigation demonstrates that blocking material, in the form of sera of rats carrying progressively growing polyoma tumors and low pH eluates of polyoma tumor tissue inoculated into polyoma isografted rats, cause an enhanced tumor growth. Corresponding serum from rats carrying an MCA-induced sarcoma and eluate from such tumor tissue had no significant enhancing effect. The administered blocking activity was detectable in the sera of the recipients for 3 days after inoculation. No delay or decrease in the level of cell-mediated anti-tumor immunity could be detected by in vitro tests for lymphocyte cytotoxicity against polyoma tumor cells. This indicates that the mechanism of the facilitated tumor growth in vitro is akin to a central or an efferent type of enhancement.