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Recombinant Human Cyclophilin A in Combination with Adoptive T-cell Therapy Improves the Efficacy of Cancer Immunotherapy in Experimental Models in vivo

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Abstract

Adoptive T-cell therapy (ACT) is successfully applied in cancer treatment; however, its efficiency can be limited by a low viability, short persistence time, and loss of functional activity of T-cells after adoptive transfer. The search for novel immunomodulators that can improve the viability, expansion, and functions of T-cells after their infusion with the minimal side effects could contribute to the development of more efficient and safe ACT strategies. Recombinant human cyclophilin A (rhCypA) is of particular interest in this respect, as it exhibits pleiotropic immunomodulatory activity and stimulates both innate and adaptive anti-tumor immunity. Here, we evaluated the effect of rhCypA on the efficacy of ACT in the mouse EL4 lymphoma model. Lymphocytes from transgenic 1D1a mice with an inborn pool of EL4-specific T-cells were used as a source of tumor-specific T-cells for ACT. In models of immunocompetent and immunodeficient transgenic mice, the course (3 days) rhCypA administration was shown to significantly stimulate EL4 rejection and prolong the overall survival of tumor-bearing mice after adoptive transfer of lowered doses of transgenic 1D1a cells. Our studies showed that rhCypA significantly improved the efficacy of ACT by enhancing the effector functions of tumor-specific cytotoxic T-cells. These findings open up the prospects for the development of innovative strategies of adoptive T-cell immunotherapy for cancer using rhCypA as an alternative to existing cytokine therapies.

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Abbreviations

Ab:

antibody

ACT:

adoptive cell therapy

CTL:

cytotoxic T-lymphocyte

CypA:

cyclophilin A

Kb:

major histocompatibility complex H2-Kb

rhCypA:

recombinant human CypA

TCR:

T-cell receptor

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Funding

This work was supported by the Russian Science Foundation (project no. 22-75-00004; https://rscf.ru/en/project/22-75-00004/).

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Authors and Affiliations

  1. N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478, Moscow, Russia

    Anastasiia A. Kalinina, Dmitry B. Kazansky & Ludmila M. Khromykh

Authors
  1. Anastasiia A. Kalinina
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  2. Dmitry B. Kazansky
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  3. Ludmila M. Khromykh
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Contributions

A.A.K., L.M.K., D.B.K. – conceptualization; L.M.K., D.B.K. – supervision and data curation; A.A.K. – in vivo and ex vivo experiments; A.A.K., L.M.K., D.B.K. – discussion of results; A.A.K. – writing of the original draft; L.M.K., D.B.K., A.A.K. – reviewing and editing; A.A.K. – funding acquisition. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Anastasiia A. Kalinina.

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The authors declare no conflicts of interest. This study was carried out in compliance with all applicable international, national, and institutional guidelines for the care and use of laboratory animals.

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Kalinina, A.A., Kazansky, D.B. & Khromykh, L.M. Recombinant Human Cyclophilin A in Combination with Adoptive T-cell Therapy Improves the Efficacy of Cancer Immunotherapy in Experimental Models in vivo. Biochemistry Moscow 88, 590–599 (2023). https://doi.org/10.1134/S0006297923050024

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  • DOI: https://doi.org/10.1134/S0006297923050024

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