№66. Cancer immunotherapy
- V.M. Moiseyenko, N.M. VolkovDOI 10.31917/1702053
In this lecture the major steps in the development of the knowledge on anticancer immunity and cancer immunotherapy are reviewed. The timeline covers the period starting from pioneering work made by William Coley up to present moment. The development of vaccines, cytokine therapy, adoptive therapy, clinical applications of antibodies and immune check-point inhibitors for cancer therapy are discussed.
Keywords: anticancer immunity, cancer immunotherapy, history, vaccines, cytokines, adoptive therapy, antibody, immune check-point inhibitor
- Z.G. Kadagidze, A.I. ChertkovaDOI 10.31917/1702062
Relationship between tumor and immune system is mediated by balance between immune activation and suppression. The dual character of interaction between immune system and tumors currently viewed as a dynamic process of cancer immunoediting. A different population of cells of innate and adaptive immunity: NK-, T-, NKT-cells, macrophages and dendritic cells display a value for anti-tumor immune response. These are heterogenic populations of cells with immunosuppressive and anti-tumor activities. Herein, we characterize main population of immunocompetent cells, effectors and suppressors, as well as their role in the anti-tumor immune response.
Keywords: cancer immunoediting, T-effectors, regulatory T cells, NK cells, NKT cells, macrophages, myeloid-derived suppressor cells
- A.A. Rumyantsev, S.A. TjulandinDOI 10.31917/1702074
In this article we described briefly the mechanism of action of modern immunotherapeutic drugs which act as inhibitors of CTLA-4 and PD-1 immune checkpoints. The most recent clinical data about efficacy of ipilimumab, nivolumab, pembrolizumab and atezolizumab in the treatment of advanced melanoma, non-small cell lung cancer, renal cell carcinoma as well as head and neck cancer were outlined. We summarized briefly the main advantages and safety profile of listed immunotherapeutics. We also discussed the contemporary evidence about potential prognostic and predictive role of known biomarkers which may help to select patients for this kind of treatment. Current regulatory status of immunotherapeutic agents and future directions of development for these drugs were also highlighted.
Keywords: drug therapy, immunotherapy, CTLA-4, PD-1, PD-L1, check-points, programmed cell death protein, nivolumab, pembrolizumab, ipilimumab, atezolizumab, biomarkers, efficacy
- N.M. VolkovDOI 10.31917/1702090
Taking into consideration the major role of cellular immunity in tumor rejection mechanisms it is very logical to use ex vivo expanded immune cells for anti-cancer therapy. Adoptive immunotherapy employs several types of cells: dendritic cells, natural killers, LAK, T-lymphocytes. Also novel genetically engineered Т-cell approaches using T-cell receptor and chimeric antigen receptor transfection are studied. This paper reviews current knowledge on the principles of adoptive cellular immunotherapy for cancer and the most notable clinical trials results.
Keywords: сell-based immunotherapy, adoptive therapy, dendritic cell, vaccine, T-lymphocyte, natural killer, cancer
- V.A. ChubenkoDOI 10.31917/1702099
The immune system is regulated by cytokines. They are included into three groups: interleukins, interferons and colony stimulating agents. This review is dedicated to the analysis of their biology and functions from the point of view of the application in clinical practice. In most, the role of this proteins is contradictory, variety and duplicated in a tumour microenvironment. It results in development of the wide spectrum of immune therapeutic strategies in malignancies. A basic problem is absence of the predictive biomarker for the selection of the patients. To select the most effective therapy the perspective methods of the treatment decisions are discussed in this article.
Keywords: immune system, cytokines, interleukins, interferons, colony stimulating agents, microenvironment, strategies of the immunotherapy
- G.Yu. Kharkevich, K.V. OrlovaDOI 10.31917/1702110
Drugs, overcoming immunological tolerance, refer to the new direction of management – Immuno-Oncology. The effectiveness of this group of drugs already proved with a number of malignancies such as melanoma of the skin, non-small cell lung cancer, clear cell renal cell cancer, bladder cancer, Merkel cell carcinoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. In this review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1 based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.
Keywords: immune-related adverse events, skin toxicity, colitis, hepatitis, anti-CTLA-4, anti-PD-1, hypophysitis, melanoma