Biomedical Research Project
In loving memory of Prof. Nikolay N. Trapeznikov
ALLOGENEIC KIR-BASED IMMUNOTHERAPY OF MALIGNANT DISEASES WITH HIGH RISK OF RELAPSE
- FGBU Blokhin Russian Cancer Research Center of the Ministry of Healthcare of Russia (Moscow, Russia)
- ZAO NeuroVita Clinic of Interventional and restorative Neurology and Therapy Russia (Moscow, Russia)
- AO Biomedical Cell Products (Moscow, Russia)
- ZAO Akrus (Moscow, Russia)
The project is aimed at the development of the novel anti-tumor biotherapeutic technologies and biomedical cell products that can completely cure and/or prevent tumor relapse and tumor metastases of various types of cancers, sarcomas and other malignant disorders. The project relies on the unique experimental and clinical research of the team of the Russian oncologists under the supervision of the academician of the Russian Academy of Sciences Prof. Nikolay Trapeznikov held in the Blokhin Russian Cancer Research Center (RCRC) from 1982 to 19993. Using the principle of histocompatibility and alloreactivity of the bone marrow of the donor and recipient, the Russian scientists studied the immunological phenomena known as graft-versus-tumor effect (GvT) and graft-versus-host disease (GvHD) induced by allogeneic transplantation of the bone marrow (allo-bone marrow) in different groups of cancer cases. The effectiveness of their method was 41% of complete cure and recovery in the cases of the solid tumors and 56% of the cases showed long-term remission and no metastases for 4 to 10 years. The pioneer research and novel results of the therapy of various types of malignancies appeared forgotten in the time of the USSR breakup and social and economic turmoil of the 90-s and even more because of the death of the leader Prof. Nikolay N. Trapeznikov. However, now professor’s students and followers have resumed his research enriching it with the advances of the scientific progress and new evidence of immunology and cancer biology. In this project we deal with allogeneic immunotherapy (alloIT) as viewed from the molecular-biological point of contemporary oncology. We do not plan complete replacement of the cells of the immune system of the patient as in alloIT after the high-dose therapy; we will partially replace the cells of the immune control and surveillance (natural killer (NK) cells and T cells) for the analogous donor cells. AlloIT is achieved by the transfusion of the allogeneic biomedical cell product (allogeneic bone marrow+allogeneic mesenchymal stromal stem cells (SCs) +/- hematopoietic SCs) along with immunosuppression for further development of the anti-cancer immune response represented as controlled GvT. The project proposes to match the donor and recipient according to the HLA-compatibility of the major histocompatibility complex (MHC) of I and II classes, blood group, Rh factor and blood phenotype, and alloreactivity of the donor and recipient is evaluated by the non-coincidence of the repertoire of Killer-cell immunoglobulin-like receptors (KIRs) (the receptors NK) and blood T-lymphocytes surface markers. The treatment consists of two independent stages of the immune therapy (IT). At the first (preparatory) stage IT is given to reduce the risk of complications of the consequent alloIT. Depending on the immune and interferon status the cytokine-therapy, adoptive immunotherapy, anti-cancer dendritic vaccines, cytotoxic lymphocytes, immunomodulators, immunosuppressors and other will be used. The goal of this stage of IT is restoration of the immune balance of the patient. The second (main) stage of the IT is KIR-based alloIT that involves administration of the biomedical cell preparation after immunosuppressive chemotherapy. The proposed alloIT is an alternative to the anti-tumor therapy in the cases of high risk of relapse or metastases cancers when the chemo- and radiotherapies are impossible as well as the measure of prevention.