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Current strategies for intratumoural immunotherapy - Beyond immune checkpoint inhibition.

Department of Translational Oncology and Early Oncology Development, Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: jianda.yuan@merck.com. Department of Translational Oncology and Early Oncology Development, Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: anuradha.khilnani@merck.com. Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA. Electronic address: joshua.brody@mssm.edu. Seven and Eight Biopharmaceuticals Inc., 343 Thornall Street, Suite 520, Edison, NJ, 08837, USA. Electronic address: robert.andtbacka@gmail.com. Department of Internal Medicine-Oncology, Huntsman Cancer Institute, University of Utah, 2000 Cir of Hope Dr #1950, Salt Lake City, UT, 84112, USA. Electronic address: SHu-Lieskovan@mednet.ucla.edu. Department of Hematology/Oncology, University of Pittsburgh Hillman Cancer Center, 5115 Centre Ave, Pittsburgh, PA, 15232, USA. Electronic address: jluke@medicine.bsd.uchicago.edu. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Electronic address: ADiab@mdanderson.org. Department of Therapeutic Innovation and Early Trials, Gustave Roussy, University of Paris-Saclay, 114 Rue Edouard Vaillant, 94805 Villejuif, France. Electronic address: AURELIEN.MARABELLE@gustaveroussy.fr. Department of Translational Oncology and Early Oncology Development, Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: snyderalex@gmail.com. Department of Translational Oncology and Early Oncology Development, Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: zhu.cao@merck.com. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA. Electronic address: stephen_hodi@dfci.harvard.edu.

European journal of cancer (Oxford, England : 1990). 2021;:493-510
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Abstract

Immunotherapy has revolutionised cancer treatment through restoration of host antitumour immune response. Immune checkpoint inhibitors (ICIs) confer durable responses in only a subset of patients. Mechanisms of ICI resistance to improve durable response rates and overall survival are an area of intense clinical research. Robust clinical development is ongoing to evaluate novel combination therapies to overcome ICI resistance, including targeting immunoregulatory pathways in the tumour microenvironment. Intratumoural (IT) immunotherapies such as toll-like receptor agonists, stimulator of interferon-induced gene agonists, retinoic-inducible gene I-like receptor agonists and oncolytic viruses may represent potential combination treatment options to overcome ICI resistance. Use of IT immunotherapies in combination with ICIs may alter the tumour microenvironment to address resistance mechanisms and improve antitumour response. Optimisation of IT immunotherapy clinical trials will elucidate resistance mechanisms, facilitate clinical trial design, define pharmacodynamic predictors that identify patients who may most benefit and inform clinical development of combination immunotherapy regimens. Here we provide an overview of IT immunotherapy principles, mechanisms of action, categories of IT immunotherapeutics, emerging data, clinical development strategies, response assessment, dose and schedule determination, clinical trial design and translational study design.

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Publication Type : Review

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