Immune response to haptenized tumor antigen as possible mechanism of anticancer action of hypoxic bioreductive agents at low doses.
Possible anticancer effect mechanism of hypoxic bioreductive agents (HBA) at low nongenotoxic doses are reviewed. Experimental and clinical investigations show the process which can develop step-by-step when injecting HBA into the tumor-bearing organism resulting in the stimulation of antitumor immunity: HBA activation in hypoxic tumor tissue, conjugation of activated HBA with proteins of tumor cells, antigen processing, presentation of neoantigen epitops in association with major histocompatibility complex-I and cytolysis of these tumor cells by T-killers. The present process can be a variant of the delayed-type hypersensitivity reaction in the tumor region. The direct regulating influence of HBA on immunocompetent and/or tumor cells as a result of interaction of these drugs with superficial or intercellular receptors is supposed to be realized additively with this process. It is concluded that the ability of HBA to selective activation in tumor tissue and formation of immunogenic conjugates with tumor proteins can be a starting-point for developing drugs with immuno-modulation anticancer properties.
Schepetkin
I
I
Department of Immunology, Tomsk Research Center, Russian Academy of Medical Science, Russia. oncology@info.tsu.ru
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects*; D006241:Haptens; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D006241:Haptens