Статья

Adoptive immunotherapy beyond CAR T-cells

A. Titov, E. Zmievskaya, I. Ganeeva, A. Valiullina, A. Petukhov, A. Rakhmatullina, R. Miftakhova, M. Fainshtein, A. Rizvanov, E. Bulatov,
2021

Adoptive cell immunotherapy (ACT) is a vibrant field of cancer treatment that began progressive development in the 1980s. One of the most prominent and promising examples is chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of B-cell hematologic malignancies. Despite success in the treatment of B-cell lymphomas and leukemia, CAR T-cell therapy remains mostly ineffective for solid tumors. This is due to several reasons, such as the heterogeneity of the cellular composition in solid tumors, the need for directed migration and penetration of CAR T-cells against the pressure gradient in the tumor stroma, and the immunosuppressive microenvironment. To substantially improve the clinical efficacy of ACT against solid tumors, researchers might need to look closer into recent developments in the other branches of adoptive immunotherapy, both traditional and innovative. In this review, we describe the variety of adoptive cell therapies beyond CAR T-cell technology, i.e., exploitation of alternative cell sources with a high therapeutic potential against solid tumors (e.g., CAR M-cells) or aiming to be universal allogeneic (e.g., CAR NK-cells, γδ T-cells), tumor-infiltrating lymphocytes (TILs), and transgenic T-cell receptor (TCR) T-cell immunotherapies. In addition, we discuss the strategies for selection and validation of neoantigens to achieve efficiency and safety. We provide an overview of non-conventional TCRs and CARs, and address the problem of mispairing between the cognate and transgenic TCRs. Finally, we summarize existing and emerging approaches for manufacturing of the therapeutic cell products in traditional, semi-automated and fully automated Point-of-Care (PoC) systems. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • A. Titov
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420008, Russian Federation
  • E. Zmievskaya
    Laboratory of Transplantation Immunology, National Hematology Research Centre, Moscow, 125167, Russian Federation
  • I. Ganeeva
    Institute of Hematology, Almazov National Medical Research Center, Saint Petersburg, 197341, Russian Federation
  • A. Valiullina
    Mircod Biotech Inc., Boca Raton, FL 33432, United States
  • A. Petukhov
    Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russian Federation
  • A. Rakhmatullina
  • R. Miftakhova
  • M. Fainshtein
  • A. Rizvanov
  • E. Bulatov
Название журнала
  • Cancers
Том
  • 13
Выпуск
  • 4
Страницы
  • 1-23
Ключевые слова
  • chimeric antigen receptor; epitope; T lymphocyte receptor; adoptive immunotherapy; bioinformatics; cancer immunotherapy; chimeric antigen receptor natural killer cell immunotherapy; chimeric antigen receptor T-cell immunotherapy; cross reaction; epitope mapping; gamma delta T lymphocyte; hematologic malignancy; human; natural killer cell; nonhuman; patient safety; Review; signal transduction; tumor associated leukocyte; whole exome sequencing
Издатель
  • MDPI AG
Тип документа
  • Review
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus