Head of the laboratory- Apollinaria V. Bogolyubova—Kuznetsova , Candidate of Biological Sciences
The Laboratory of Transplantation Immunology is part of the Management Division of Biomedical Technologies. It was founded at the NMRC for Hematology in 2015. The main scientific goals of the laboratory are the development of methods for the prevention and therapy of hematological diseases based on T—lymphocytes and the identification of features of the T-cell immune response to various pathogens, including the SARS-CoV-2 virus.
CURRENT LABORATORY RESEARCH TOPICS:
Development of CAR-T-cell drugs for the treatment of blood malignancies
A relatively new method of treating tumors of the hematopoietic system is the use of lymphocytes with a chimeric antigen receptor specific to the tumor antigen – CAR-T.
The laboratory staff is developing an original anti-CD19 CAR-T-cell drug for the treatment of B-cell malignancies. In addition, research is underway to create a "universal" CAR-T-cell platform, with the help of which it will be possible to obtain CAR-T cells specific to a given human antigen.
Study of the T-cell response to the SARS-CoV-2 virus
To create diagnostic systems and vaccines against coronavirus, it is necessary to study the interactions of human immunity with the virus.
The laboratory staff is looking for new sites (epitopes) of the virus, to which an immune response and immunological memory are formed, and also studying T-cell immunity in patients who have had COVID-19, people who have not had COVID-19 and in those that have been vaccinated against SARS-CoV-2.
Publications:
- SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T cell receptors. A. Shomuradova, M. Vagida, S. Sheetikov, K. Zornikova, D. Kiryukhin, A. Titov, I. Peshkova, A. Khmelevskaya, D. Dianov, M. Malasheva, A. Shmelev, Y. Serdyuk, D. Bagaev, A. Pivnyuk, D. Shcherbinin, A. Maleeva, N. Shakirova, A. Pilunov, D. Malko, E. Khamaganova, B. Biderman, A. Ivanov, M. Shugay, G. Efimov. Immunity (Dec 2020) doi.org/10.1016/j.immuni.2020.11.004;
- Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection. A. Minervina, E. Komech, A. Titov, M. Koraichi, E. Rosati, I. Mamedov, A. Franke, G. Efimov, D. Chudakov, T. Mora, A. Walczak, Y. Lebedev, M. Pogorelyy arXiv:2005.08290v3.
· Minervina AA, Komech EA, Titov A, Bensouda Koraichi M, Rosati E, Mamedov IZ, Franke A, Efimov GA, Chudakov DM, Mora T, Walczak AM, Lebedev YB, Pogorelyy MV. Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection. Elife. 2021 Jan 5;10:e63502. doi: 10.7554/eLife.63502. PMID: 33399535; PMCID: PMC7806265.
· Goncharov M, Bagaev D, Shcherbinin D, Zvyagin I, Bolotin D, Thomas PG, Minervina AA, Pogorelyy MV, Ladell K, McLaren JE, Price DA, Nguyen THO, Rowntree LC, Clemens EB, Kedzierska K, Dolton G, Rius CR, Sewell A, Samir J, Luciani F, Zornikova KV, Khmelevskaya AA, Sheetikov SA, Efimov GA, Chudakov D, Shugay M. VDJdb in the pandemic era: a compendium of T cell receptors specific for SARS-CoV-2. Nat Methods. 2022 Sep;19(9):1017-1019. doi: 10.1038/s41592-022-01578-0. PMID: 35970936.
· Titov A, Shaykhutdinova R, Shcherbakova OV, Serdyuk YV, Sheetikov SA, Zornikova KV, Maleeva AV, Khmelevskaya A, Dianov DV, Shakirova NT, Malko DB, Shkurnikov M, Nersisyan S, Tonevitsky A, Khamaganova E, Ershov AV, Osipova EY, Nikolaev RV, Pershin DE, Vedmedskia VA, Maschan M, Ginanova VR, Efimov GA. Immunogenic epitope panel for accurate detection of non-cross-reactive T cell response to SARS-CoV-2. JCI Insight. 2022 May 9;7(9):e157699. doi: 10.1172/jci.insight.157699. PMID: 35389886; PMCID: PMC9090254.
· Wu D, Kolesnikov A, Yin R, Guest JD, Gowthaman R, Shmelev A, Serdyuk Y, Dianov DV, Efimov GA, Pierce BG, Mariuzza RA. Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors. Nat Commun. 2022 Jan 10;13(1):19. doi: 10.1038/s41467-021-27669-8. PMID: 35013235; PMCID: PMC8748687.
· Molodtsov IA, Kegeles E, Mitin AN, Mityaeva O, Musatova OE, Panova AE, Pashenkov MV, Peshkova IO, Alsalloum A, Asaad W, Budikhina AS, Deryabin AS, Dolzhikova IV, Filimonova IN, Gracheva AN, Ivanova OI, Kizilova A, Komogorova VV, Komova A, Kompantseva NI, Kucheryavykh E, Lagutkin DА, Lomakin YA, Maleeva AV, Maryukhnich EV, Mohammad A, Murugin VV, Murugina NE, Navoikova A, Nikonova MF, Ovchinnikova LA, Panarina Y, Pinegina NV, Potashnikova DM, Romanova EV, Saidova AA, Sakr N, Samoilova AG, Serdyuk Y, Shakirova NT, Sharova NI, Sheetikov SA, Shemetova AF, Shevkova LV, Shpektor AV, Trufanova A, Tvorogova AV, Ukrainskaya VM, Vinokurov AS, Vorobyeva DA, Zornikova KV, Efimov GA, Khaitov MR, Kofiadi IA, Komissarov AA, Logunov DY, Naigovzina NB, Rubtsov YP, Vasilyeva IA, Volchkov P, Vasilieva E. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific T Cells and Antibodies in Coronavirus Disease 2019 (COVID-19) Protection: A Prospective Study. Clin Infect Dis. 2022 Aug 24;75(1):e1-e9. doi: 10.1093/cid/ciac278. PMID: 35435222; PMCID: PMC9047235.
The study of the immune response to minor histocompatibility antigens and the creation of a method of T-cell therapy for leukemia
The most severe side effect of transplantation is the "graft versus host" reaction. It can occur even if the donor and the patient are fully compatible with HLA (human leukocyte antigens), since donor cells can respond to minor histocompatibility antigens (mHAgs) in the patient's body. They are different due to genetic differences between different people.
The laboratory searches for the mHAgs that most often cause an immune response during transplantation, and studies the parameters of the immune response in patients after transplantation. The study is aimed at more successful selection of donor—patient pairs during blood cell transplantation.
The immune response to mHAgs may also have therapeutic applications. Thus, the laboratory staff uses the NA-1 antigen on the surface of blood cells as a target in the developed approach to leukemia therapy. The introduction of a receptor that recognizes NA-1 into the donor's T-lymphocytes will allow them us recognize and destroy residual leukemia cells that survived chemotherapy and transplantation, which should reduce the risk of relapse.
Publications:
- Rapid Multiplex Genotyping of 20 HLA-A*02:01 Restricted Minor Histocompatibility Antigens. D. Romaniuk, A. Postovskaya, A. Khmelevskaya, D. Malko, G. Efimov. Frontiers in Immunology (Jun 2019) 10: 1226 frontiersin.org/articles/10.3389/fimmu.2019.01226/full;
- In Silico Analysis of the Minor Histocompatibility Antigen Landscape Based on the 1000 Genomes Project. N. Bykova, D. Malko, G. Efimov. Frontiers in Immunology (Aug 2018) 9: 1819 frontiersin.org/articles/10.3389/fimmu.2018.01819/full;
- Transgenic lymphocytes targeting minor histocompatibility antigens for post-transplant immunotherapy. A. Pilunov, D. Romaniuk, S. Sheetikov, A. Khmelevskaya, A. Shmelev, N. Bykova, A. Shomuradova, D. Kiryukhin, D. Dianov, G. Efimov. Cytotherapy (May 2020) 22: 5 (Supplement), S124 sciencedirect.com/science/article/pii/S1465324920302978;
- Development of T-Cell Therapy Targeting Hematopoietic Minor Histocompatibility Antigen HA-1. A. Pilunov, D. Romaniuk, S. Sheetikov, A. Khmelevskaya, A. Shmelev, N. Bykova, A. Shomuradova, D. Kiryukhin, D. Dianov, G. Efimov, V. Savchenko. Blood (Nov 2019) 134 (Supplement 1): 5749 doi.org/10.1182/blood-2019-130552.
Creation of a T-cell vaccine against cytomegalovirus infection
The NMRC for Hematology is undergoing clinical testing of the T-cell therapy method for cytomegalovirus (CMV) infection in patients after transfusion of blood stem cells from a donor. The goal of therapy is to reduce the risk of transplant rejection. To do this, a special population of donor immune cells is used which recognize and destroy cytomegalovirus-infected cells. This approach is called a "T-cell vaccine" because the T-cells injected into the patient provide an immune response to infection.
The laboratory staff is studying the T-cell response to CMV in healthy donors and patients after blood stem cell transplantation. The laboratory has developed an algorithm for matching donor—patient pairs to inject the patient with donor T cells against CMV. This algorithm is used in clinical testing. T-cells for therapy are obtained according to the international standard of Good Manufacturing Practice (GMP).
Publications:
- Abundance, diversity and functionality of cytomegalovirus-specific T cells depends on HLA genotype of the donor and hierarchy of the immunodominant epitopes. A. Maleeva, K. Zornikova, D. Kiryukhin, N. Shakirova, V. Shmarov and G. Efimov. The Journal of Immunology (May 2020) 204 (Supplement 1): 94.13 jimmunol.org/content/204/1_Supplement/94.13;
- Repertoire of Cytomegalovirus-Specific T Cells Is Focused on the Immunodominant Epitopes in Fixed Hierarchy Dependent on HLA Genotype of the Donor. A. Maleeva, V. Shmarov, D. Kiryukhin, G. Efimov, V. Savchenko. Blood (Nov 2019) 134 (Supplement 1): 2327 doi.org/10.1182/blood-2019-130241;
- CMV-specific T-cell reconstitution as a key factor for identification of candidates for CMV-specific lymphocytes infusion. A. Dmitrova, V. Shmarov, M. Drokov, L. Kuzmina, N. Popova, E. Mikhaltsova, V. Vasilyeva, M. Dovyidenko, O. Koroleva, D. Dubnyak, Z. Konova, E. Usikova, U. Maslikova, O. Starikova, D. Kiryukhin, G. Efimov, E. Parovichnikova, V. Savchenko. HemaSphere (Jun 2019) 3: S1, p 1037 doi:10.1097/01.HS9.0000567776.14469.6f.
