In the section devoted to biomedical cell products, much attention was paid mainly to the legal aspects of the circulation of this type of product, as well as to the basic procedures that make up the life cycle of BMCP. However, this article is devoted directly to BMCP – the newest and promising method of treatment of cancer, in particular oncohematological diseases, with the help of the patient’s genetically modified T-lymphocytes.

CAR-T (Chimeric antigen receptor [of] T cells) therapy is one of the newest methods of adoptive cell therapy with the help of patient’s genetically modified T-lymphocytes expressing chimeric antigen receptors (CAR) to specific tumor antigens.

The mechanism of action of this type of therapy is that due to the modified receptor, the specificity of the interaction of T-lymphocytes with the tumor cell (which leads to its destruction), as well as the activation of T-lymphocytes, is ensured.

The production technology of modified T-cells consists of several stages. First, T-cells are collected from the patient’s peripheral blood, then they are activated for subsequent modification. At the third stage, genetic modification of T-lymphocytes is carried out, with the result that chimeric receptors appear on their surface, ensuring the effectiveness of therapy. The last stage is the expansion of modified T-lymphocytes in the bioreactor. Before the introduction of cells to the patient, the quality control of the cell product is carried out – testing for microbiological safety, transduction efficiency and functional activity of T-lymphocytes.

This approach, in which cells are first removed from the patient’s body, then modified, and after that returned back is called ex vivo.

This therapy is effective in treating patients with B-cell lymphomas, chronic lymphocytic leukemia (CLL) and lymphoblastic leukemia (LL). Currently, more than 100 clinical studies are being conducted to study this type of therapy.  Cellular therapy was most effective when used in combination with chemotherapy or other types of therapy. According to Kochenderfer et al, the response to this type of combination therapy was 43% for patients with CLL. According to Maude et al. and Grupp et al. with allogeneic bone marrow transplantation followed by the introduction of modified T-lymphocytes (using CAR-T therapy), complete remission was 90%.

However, CAR-T therapy has side effects , such as: allergic reactions to animals or recombinant components, hypercytokinemia, expressed in fever, fatigue, tachycardia, nausea, etc. In addition, receptors on the surface of modified T-lymphocytes can interact with healthy cells, for example, with normal B-lymphocytes.

Thus, CAR-T therapy showed its effectiveness in the course of preclinical and clinical studies in the treatment of oncological diseases. However, it requires improvement in order to eliminate side effects.

References:

1. Павлова А.А., Масчан М.А., Пономарев В.Б. Адоптивная иммунотерапия генетически модифицированными Т-лимфоцитами, экспрессирующими химерные антигенные рецепторы. Онкогематология. 2017;12(1):17-32. https://doi.org/10.17650/1818-8346-2017-12-1-17-32
2. Kochenderfer J.N., Wilson W.H., Janik J.E. et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010;116(20): 4099–102. DOI: 10.1182/blood-2010-04-281931.
3. Kochenderfer J.N., Dudley M.E., Feldman S.A. et al. B-cell depletion and remissions of malignancy along with cytokineassociated toxicity in a clinical trial of anti- CD19 chimeric-antigen-receptortransduced T cells. Blood 2012;119(12):2709–20. DOI: 10.1182/blood-2011-10-384388
4. Maude S.L., Frey N., Shaw P.A. et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014;371(16):1507–17. DOI: 10.1056/NEJMoa1407222.
5. Grupp S.A., Kalos M., Barrett D. et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368(16):1509–18. DOI: 10.1056/NEJMoa1215134