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Review
. 2021 Sep 27;14(1):156.
doi: 10.1186/s13045-021-01164-5.

Combination strategies to maximize the benefits of cancer immunotherapy

Shaoming Zhu #  1   2 , Tian Zhang #  1   3 , Lei Zheng  1   4 , Hongtao Liu  1   5 , Wenru Song  1   6 , Delong Liu  1   7 , Zihai Li  8   9 , Chong-Xian Pan  10   11
Affiliations
Review

Combination strategies to maximize the benefits of cancer immunotherapy

Shaoming Zhu et al. J Hematol Oncol. .

Abstract

Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.

Keywords: CAR-T; Cancer vaccine; Cytokine; Immune checkpoint inhibitor; Immunotherapy; Oncolytic virus.

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Conflict of interest statement

TZ: Research funding (to Duke) from Pfizer, Janssen, Acerta, Abbvie, Novartis, Merrimack, OmniSeq, PGDx, Merck, Mirati, Astellas and Regeneron; consulting/speaking with Genomic Health and Sanofi Aventis; and consulting/advisory board with AstraZeneca, Bayer, Pfizer, Foundation Medicine, Janssen, Amgen, BMS, Calithera, Dendreon and MJH Associates; Stock ownership/employment (spouse) from Capio Biosciences, Archimmune Therapeutics and Nanorobotics. LZ: grant support from Bristol-Meyer Squibb, Merck, AstraZeneca, iTeos, Amgen, NovaRock, Inxmed and Halozyme; paid consultant/Advisory Board Member at Biosion, Alphamab, NovaRock, Ambrx, Akrevia/Xilio, Datarevive, QED, Xilio, Natera, Novagenesis, Snow Lake Captials and Mingruizhiyao; and shareholder at Alphamab and Mingruzhiyao. HL: research support from Karyopharm and Bristol Myers Squibb, served at advisory board meetings of Agios and a consultant for Beigene, NGM Biopharm. WS: an employee of Kira Pharmaceuticals. DL attended advisory board meetings of AstraZeneca, Beigene, Rigel; serves on the Speaker bureaus of AstraZeneca, Beigene, Incyte, Janssen, Pharmacyclics and Rigel; and has research fundings from Acerta, Celgene, Denovo and Pfizer. ZL: Scientific advisory board member for Heat Biologics, Alphamab (chair), Hengenix and Ioknisys. CXP is a co-founder and shareholder of LP Therapeutics.

Figures

Fig. 1
Fig. 1
Timeline of the FDA approvals of combination therapy
Fig. 2
Fig. 2
The cancer-immunity cycle, resistant mechanisms and potential solutions
See this image and copyright information in PMC

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