Combination strategies to maximize the benefits of cancer immunotherapy

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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.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

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Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

Richard S Finn, Shukui Qin, Masafumi Ikeda … (2020)

The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.

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Author and article information

Contributors

Shaoming Zhu: Urology920@163.com

Tian Zhang: tian.zhang2@duke.edu

Lei Zheng: Lzheng6@jhmi.edu

Hongtao Liu: hliu2@medicine.bsd.uchicago.edu

Wenru Song: wenru.song@kirapharma.com

Delong Liu: Delong_liu@nymc.edu

Zihai Li: zihai.li@osumc.edu

Chong-xian Pan:

ORCID: http://orcid.org/0000-0002-8588-3994

Chongxian_pan@hms.harvard.edu

Journal

Journal ID (nlm-ta): J Hematol Oncol

Journal ID (iso-abbrev): J Hematol Oncol

Title: Journal of Hematology & Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1756-8722

Publication date (Electronic): 27 September 2021

Publication date PMC-release: 27 September 2021

Publication date Collection: 2021

Volume: 14

Electronic Location Identifier: 156

Affiliations

[1 ]Chinese American Hematologist and Oncologist Network, New York, NY USA

[2 ]GRID grid.411607.5, Department of Urology, , Beijing Chao-Yang Hospital, ; Beijing, China

[3 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, , Duke University, ; DUMC 103861, Durham, NC 27710 USA

[4 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, The Sydney Kimmel Comprehensive Cancer Center, , Johns Hopkins University School of Medicine, ; Baltimore, MD 21287 USA

[5 ]GRID grid.170205.1, ISNI 0000 0004 1936 7822, University of Chicago, ; Chicago, IL USA

[6 ]Kira Pharmaceuticals, Cambridge, MA USA

[7 ]GRID grid.260917.b, ISNI 0000 0001 0728 151X, New York Medical College, ; Valhalla, NY USA

[8 ]GRID grid.261331.4, ISNI 0000 0001 2285 7943, Pelotonia Institute for Immuno-Oncology, , The Ohio State University, ; Columbus, OH USA

[9 ]GRID grid.38142.3c, ISNI 000000041936754X, Harvard Medical School, ; West Roxbury, MA 02132 USA

Author information

Chong-xian Pan http://orcid.org/0000-0002-8588-3994

Article

Publisher ID: 1164

DOI: 10.1186/s13045-021-01164-5

PMC ID: 8475356

PubMed ID: 34579759

SO-VID: a06aa93f-3fa8-483e-98bd-49497ec8134f

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 29 July 2021

Date accepted : 7 September 2021

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: immunotherapy,immune checkpoint inhibitor,cancer vaccine,oncolytic virus,car-t,cytokine

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: immunotherapy, immune checkpoint inhibitor, cancer vaccine, oncolytic virus, car-t, cytokine

Combination strategies to maximize the benefits of cancer immunotherapy

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Cancer Immunotherapy

Most cited references 315

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

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