Комбинированная терапия рака на основе онколитической виротерапии и таргетной CAR T/NK-клеточной иммунотерапии

Translated title of the contribution: Combination of Oncolytic Virotherapy and CAR T/NK Cell Therapy for the Treatment of Cancer

G. V. Kochneva, G. F. Sivolobova, A. V. Tkacheva, A. A. Gorchakov, S. V. Kulemzin

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

Multiple lines of evidence indicate that CAR-T cell based therapy and oncolytic virotherapy display robust performance in both immunocompetent and immunodeficient mouse models. Rare, yet highly successful attempts to combine these therapeutic platforms have also been reported. Interestingly, both approaches have shown pronounced efficacy in human trials, albeit these were limited to just a handful of malignancies. Specifically, CD19-specific CAR-T cell products (Kymriah and Yescarta) have been highly effective against B cell lymphomas and leukemias, whereas administering oncolytic viruses resulted in pronounced responses in melanoma (Imlygic and Rigvir) and nasopharyngeal carcinoma (Oncorine) patients. It is well established that efficacy of virotherapy as a standalone approach is largely restricted by the pre-existing and mounting immune response against viral antigens, and requires a relatively functional immune system, which is not typical for cancer patients, with the current antitumor therapy schemes. On the other hand, the most important challenges faced by the current CAR-T cell therapy formats include the lack of targetable tumor-specific surface antigens, tumor cell heterogeneity, and immunosuppressive tumor microenvironment, not to mention the unacceptably high costs. Remarkably, combining the two approaches may help address their individual bottlenecks. Namely, local acute inflammatory reaction induced by the viral infection may reverse tumor-associated immunosuppression and lead to more efficient homing and penetration of CAR-expressing lymphocytes into the tumor stroma; combined viral and CAR-mediated cytotoxicity may ensure the production of immunogenic cell debris and efficient presentation of tumor neoantigens, and potently recruit the patient's own bystander immune cells to attack cancer cells. Thus, testing the combinations of CAR-based and virolytic approaches in the clinical setting appears both logical and highly promising.

Translated title of the contributionCombination of Oncolytic Virotherapy and CAR T/NK Cell Therapy for the Treatment of Cancer
Original languageRussian
Pages (from-to)3-16
Number of pages14
JournalMolekuliarnaia biologiia
Volume54
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • anticancer immunity
  • cancer therapy
  • chimeric antigen receptors
  • NK-cells
  • oncolytic viruses
  • T-cells
  • virotherapy
  • NATURAL-KILLER-CELL
  • CHIMERIC ANTIGEN RECEPTOR
  • MODIFIED T-CELLS
  • VACCINIA VIRUS
  • ANTITUMOR-ACTIVITY
  • CHECKPOINT BLOCKADE
  • DELIVERY
  • RESPONSES
  • NK CELLS
  • IMMUNOTHERAPY

State classification of scientific and technological information

  • 34 BIOLOGY

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