Current strategies for intratumoural immunotherapy – Beyond immune checkpoint inhibition

Jianda Yuan, Anuradha Khilnani, Joshua Brody, Robert H.I. Andtbacka, Siwen Hu-Lieskovan, Jason J. Luke, Adi Diab, Aurelien Marabelle, Alexandra Snyder, Z. Alexander Cao, F. Stephen Hodi

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations

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.

Original languageEnglish
Pages (from-to)493-510
Number of pages18
JournalEuropean Journal of Cancer
Volume157
DOIs
StatePublished - Nov 2021

Keywords

  • Immunotherapy
  • Translational medical research
  • Tumour biomarkers
  • Tumour microenvironment

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