English

Abstract

Cancer is a disease of genes, with a myriad of them showing altered expression, either contributing to the cause of cancer, or consequence of it. These changes in gene expression make many alterations in cell physiology like: - 1) self-sufficiency in growth signals, 2) insensitivity to anti-growth signals, 3) evasion of apoptosis, 4) limitless replicative potential, 5) sustained angiogenesis, and 6) tissue invasion and metastasis [1]. Oncogenesis, as a result of overactivity of growth factor receptors, cytokine receptors and oncoproteins, coordinates immune evasion [2]. Tumor cells display different antigens coupled with MHC I than the normal cells. Ideally our immune system employs a defense mechanism called ‘immunological surveillance’ to detect and destroy these cancer cells, a concept proposed by Elrich in 1909 [1, 2].There are several mechanisms of escape from the immune surveillance like immunoselection of tumor antigen-negative variants, the downregulation of MHC class I expression, suppressive T cells, and the elaboration of immunosuppressive cytokines and other factors [3]. Professional APCs are endowed with the ability of ‘cross presentation’ i.e., presentation of antigens on MHC class I molecules. Cross presentation can either lead to tolerance or to immunity. If antigens are obtained themselves alone, it leads to tolerance. If antigens are acquired with immunostimulatory signals, it leads to immunity. The phenomenon of cross presentation is essential for development of immunity to tumors [4]. Immunotherapy has long been viewed as an alternative to overcome the serious side effects of treatments like chemotherapy and radiotherapy. The immune system has the potential to either promote or delay tumor onset and progression, the effectiveness of immune surveillance and the efficacy of immunotherapy depend on the balance between these diametric opposites. In leukemia one treatment option is replacing the bone marrow. Often bone marrow infused from allogeneic donor to the patient induces a beneneficial graft vs leukaemia or to say in general graft vs tumor effect In this review we are exploring strategies, in context of MHC restriction to contain this graft vs host disease and at the same time retain a sustained anti- tumor[here mainly anti-leukemia] effect. Further the use of this principle in conjunction with immunobiotechnology approaches like siRNA and allogeneic therapeutic vaccines can be extended to solid tumors.