Adoptive Immunotherapy Based on Chain-Centric TCRs in Treatment of Infectious Diseases
Anastasiia A. Kalinina,
Ludmila N. Nesterenko,
Alexandra V. Bruter,
Denis V. Balunets,
Dmitriy M. Chudakov,
Mark Izraelson,
Olga V. Britanova,
Ludmila M. Khromykh,
Dmitry B. Kazansky
Affiliations
Anastasiia A. Kalinina
Federal State Budgetary Institution ''N. N. Blokhin National Medical Research Center of Oncology'' оf the Ministry of Health of the Russian Federation, 115478 Moscow, Russia
Ludmila N. Nesterenko
''N. F. Gamaleya National Research Center of Epidemiology and Microbiology'', the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Alexandra V. Bruter
Federal State Budgetary Institution ''N. N. Blokhin National Medical Research Center of Oncology'' оf the Ministry of Health of the Russian Federation, 115478 Moscow, Russia; Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Denis V. Balunets
''N. F. Gamaleya National Research Center of Epidemiology and Microbiology'', the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Dmitriy M. Chudakov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Mark Izraelson
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Olga V. Britanova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Ludmila M. Khromykh
Federal State Budgetary Institution ''N. N. Blokhin National Medical Research Center of Oncology'' оf the Ministry of Health of the Russian Federation, 115478 Moscow, Russia
Dmitry B. Kazansky
Federal State Budgetary Institution ''N. N. Blokhin National Medical Research Center of Oncology'' оf the Ministry of Health of the Russian Federation, 115478 Moscow, Russia; Corresponding author
Summary: Complications after vaccination, lack of vaccines against certain infections, and the emergence of antibiotic-resistant microorganisms point to the need for alternative ways of protection and treatment of infectious diseases. Here, we proposed a therapeutic approach to control salmonellosis based on adoptive cell therapy. We showed that the T cell receptor (TCR) repertoire of salmonella-specific memory cells contains 20% of TCR variants with the dominant-active α-chain. Transduction of intact T lymphocytes with the dominant salmonella-specific TCRα led to their enhanced in vitro proliferation in response to salmonella. Adoptive transfer of transduced T cells resulted in a significant decrease in bacterial loads in mice infected with salmonella before or after the adoptive transfer. We demonstrated that adoptive immunotherapy based on T cells, transduced with dominant-specific TCRα could be successfully applied for treatment and prevention of infectious diseases and represent a useful addition to vaccination and existing therapeutic strategies.
