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

doi:10.1016/j.isci.2020.101854

Adoptive Immunotherapy Based on Chain-Centric TCRs in Treatment of Infectious Diseases

iScience. 2020 Nov 24;23(12):101854. doi: 10.1016/j.isci.2020.101854. eCollection 2020 Dec 18.

Authors

Anastasiia A Kalinina¹, Ludmila N Nesterenko², Alexandra V Bruter^{1

3}, Denis V Balunets², Dmitriy M Chudakov⁴, Mark Izraelson⁴, Olga V Britanova⁴, Ludmila M Khromykh¹, Dmitry B Kazansky¹

Affiliations

¹ 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.
² "N. F. Gamaleya National Research Center of Epidemiology and Microbiology", the Ministry of Health of the Russian Federation, 123098 Moscow, Russia.
³ Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
⁴ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.

Abstract

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.

Keywords: Immunology; Microbiology.