Transfer tumorspezifischer Immunit�t mit ?Immun? RNA: Aussichten f�r eine Krebstherapie

Abstract

Ribonucleic acids extracted from specifically sensitized lymphoid cells (I-RNA) have been shown to transfer specific immunoreactivity to normal non-immune lymphoid cells. Evidence for the transfer by I-RNA, of immune responses to tumor-associated antigens of animal and human neoplasms, in vivo and in vitro, is reviewed. Results obtained in our laboratory and in other laboratories indicate that xenogeneic, allogeneic and syngeneic I-RNA extracts mediate specific cytotoxicity to tumor cells, in vitro, and mediate transplantation resistance and tumor rejection responses in vivo. Our results suggest that I-RNA preparations fail to elicit immune responses directed against "self" antigens. By contrast, I-RNA's directed against "non-self" tumor-associated antigens appear to induce lymphocytes to effect specific anti-tumor immune responses. The mechanisms responsible for the failure of I-RNA to initiate immune responses against "self" antigens are not known at present and demand investigation. Preliminary results of a clinical Phase I trial of immunotherapy with xenogeneic I-RNA in selected cancer patients are reviewed. I-RNA might offer promise as a new modality for the immunotherapy of human cancer.

Conversion of human lymphocytes to antitumor immune reactivity by xenogeneic and allogeneic imune RNA detected by leukocyte-adherence inhibition tests

“…In both animal and human tumor systems we have previously reported that xenogeneic and allogeneic I-RNA mediated immune responses, in vivo and in vitro, which were specific for the tumor or the histologic type of tumor used to immunize the I-RNA donor [22,23,29]. However, in most of our previous in vitro studies, cellular antitumor immune responses mediated by I-RNA were detected and measured by microcytotoxicity tests [9,[17][18][19][20][21][22][23], by tests for inhibition of macrophage migration [40], or by lymphocyte blastogenesis assays [5]. Suspicion has been raised that incubation of I-RNA treated lymphoid cells containing macrophages with tumor antigens might generate RNA-antigen complexes [12,13], which might facilitate in vitro sensitization of effector cells during long-term incubation in vitro.…”

“…Our previous studies, utilizing microcytotoxicity tests, suggested that normal lymphocytes treated with xenogeneic antitumor I-RNA mediated cellular immune responses to species and/or histocompatibility antigens as well as to tumor antigens [9]. In order to demonstrate tumor-specific immunity, lymphoid effector cells treated with xenogeneic antitumor I-RNA had to be syngeneic in the case of animal tumors [19,22,30], or autologous in the case of human tumors [17,[20][21][22], with respect to the tumor target cells.…”