350 rub
Journal Technologies of Living Systems №1 for 2021 г.
Article in number:
Key immune checkpoints and their inhibitors in the therapy of bone tumors. Part 2. Additional targets for immunotherapy of bone tumors and markers of its efficiency
DOI: 10.18127/j20700997-202101-02
UDC: 616.71-006-085:612.017.1
Keywords: Bone tumors CTLA-4 B7-H3 NKG2D/NKG2DL HLA-G immunotherapy.
Authors:

A.A. Alferov¹, M.M. Efimova², Yu.B. Kuzmin³, I.N. Kuznetsov4, E.S. Gershtein5, N.E. Kushlinskii6

1–3, 5, 6 N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of the Russian Federation (Moscow, Russia)

4 A.I. Evdokimov Moscow University of Medicine and Dentistry of Ministry of Health           of the Russian Federation (Moscow, Russia)

Abstract:

The intent interest of oncologists in bone sarcomas is imposed by the prevalence of these diseases at advanced stages in children, adolescent and young people, its aggressiveness, resistance to chemotherapy, and unfavorable prognosis. Blockade of the signaling system of programmed cell death 1 receptor protein PD-1/PD-L is the most well-known, actively applied and clinically effective method of immune checkpoints targeted antitumor immunotherapy. However, the recent experience shows that the most promising approach could be a complex blockade of two or more immune checkpoints.

Aim of the work – analysis of the clinical implications of the investigation of expression and blockade of such immune checkpoints as CTLA-4, B7-H3, NKG2D/NKG2DL, HLA-G, etc. in primary bone tumor patients.

Currently, the exploration of additional targets for immunotherapy and biological markers for assessment of its efficiency in oncological patients is under investigation. The study of the prognostic value of TILs, PD-1/PD-L1, HLA, CTLA-4, B7-H3, NKG2D/NKG2DL, CSPG4, LAG-3, GITR in the immunotherapy of malignant tumors including bone sarcomas actively proceeds. In this review, the main and just appearing immune checkpoints’ inhibitors, which are experimentally explored and undergo the first clinical trials for the treatment of bone sarcomas are described. The majority of current investigations from basic studies to clinical trials of blocker drugs are still at initial stages. The principal results of these studies describe the assessment of the efficiency of immunotherapy of various bone sarcomas with single immune checkpoint blockers or in combined regimens and their potential irAE – immune-related adverse effects.

Active development of the studies of various immune checkpoints, search of the drugs targeted on their suppression and biological markers of their efficiency allow to expect that in the nearest future standardized panels of screening biomarkers for the immunotherapy of such severe disease as bone sarcomas would be found.

Pages: 18-31
For citation

Alferov A.A., Efimova M.M., Kuzmin Yu.B., Kuznetsov I.N., Gershtein E.S., Kushlinskii N.E. Key immune checkpoints and their inhibitors in the therapy of bone tumors. Part 2. Additional targets for immunotherapy of bone tumors and markers of its efficiency. Technologies of living systems. 2021. V. 18. № 1. P. 18–31. DOI: 10.18127/j20700997-20210102 (In Russian).

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Date of receipt: 20.07.2020
Approved after review: 24.08.2020
Accepted for publication: 25.09.2020