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The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy

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Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada
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Department of Experimental Therapeutics, Thoreau Laboratory for Global Health, M2D2, University of Massachusetts, Lowell, MA 01852, USA
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Department of Immunology and Allergy, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
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Division of Hematology & Oncology, Department of Pediatrics, Ali-Asghar Children Hospital, Iran University of Medical Science, Tehran 1449614535, Iran
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QPS, Holdings LLC, Pencader Corporate Center, 110 Executive Drive, Newark, DE 19702, USA
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The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5G 1M1, Canada
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Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto, Toronto, ON M5G 1M1, Canada
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Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
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KaviKrishna Laboratory, Department of Cancer and Stem Cell Biology, GBP, Indian Institute of Technology, Guwahati 781039, India
*
Authors to whom correspondence should be addressed.
Co-First/Equal authorship: These authors contributed equally to this work.
Academic Editors: Damiana Álvarez-Errico and Lorea Villanueva
Cancers 2021, 13(14), 3596; https://doi.org/10.3390/cancers13143596
Received: 14 June 2021 / Revised: 13 July 2021 / Accepted: 14 July 2021 / Published: 18 July 2021
(This article belongs to the Special Issue Epigenetics and Cancer Immunotherapy)
Drug development and therapeutic approaches for treating cancer have shifted towards incorporating more multimodality approaches that harness the immune system. Despite innovative and notable advances in immunotherapy, challenges associated with variations in patient response rates and efficacies on select tumors minimize the overall effectiveness of these immunotherapy approaches. This review provides an overview of the current immunotherapy options available, followed by epigenetic immunomodulators that may enhance and transmogrify immunotherapy effectiveness. These approaches are positioned to harness trained immunity, improve immune response rates, and increase the efficacy of immunotherapies.
Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy. View Full-Text
Keywords: immunotherapy; cancer stem cells; oncolytic viral therapy; COVID-19; gut microbiota; drug resistance; combination immunotherapy; CAR T cell therapy; diet; epigenetic therapies; hTERT vaccines; telomerase-targeted immunotherapy immunotherapy; cancer stem cells; oncolytic viral therapy; COVID-19; gut microbiota; drug resistance; combination immunotherapy; CAR T cell therapy; diet; epigenetic therapies; hTERT vaccines; telomerase-targeted immunotherapy
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MDPI and ACS Style

Mokhtari, R.B.; Sambi, M.; Qorri, B.; Baluch, N.; Ashayeri, N.; Kumar, S.; Cheng, H.-L.M.; Yeger, H.; Das, B.; Szewczuk, M.R. The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy. Cancers 2021, 13, 3596. https://doi.org/10.3390/cancers13143596

AMA Style

Mokhtari RB, Sambi M, Qorri B, Baluch N, Ashayeri N, Kumar S, Cheng H-LM, Yeger H, Das B, Szewczuk MR. The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy. Cancers. 2021; 13(14):3596. https://doi.org/10.3390/cancers13143596

Chicago/Turabian Style

Mokhtari, Reza B., Manpreet Sambi, Bessi Qorri, Narges Baluch, Neda Ashayeri, Sushil Kumar, Hai-Ling M. Cheng, Herman Yeger, Bikul Das, and Myron R. Szewczuk. 2021. "The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy" Cancers 13, no. 14: 3596. https://doi.org/10.3390/cancers13143596

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