Nature reviews. Clinical oncology

Injecting cancer immunotherapies directly into tumors and targeting them to tumor tissue

Updated

Abstract

Intratumoural delivery of immune therapies may significantly enhance their efficacy against tumors.

  • Systemic biodistribution of immune-checkpoint inhibitors and CAR T cells raises safety concerns.
  • Directly targeting immune cells or factors to tumors could improve the bioavailability of immunotherapies.
  • In mouse models, intratumoural administration of various agents has shown powerful effects on both injected and uninjected tumors.
  • Biotechnology strategies aim to achieve higher concentrations of immune mediators in tumor tissues by targeting specific elements or using specially designed agents.
  • Ongoing clinical trials are assessing these strategies but face challenges related to administration methods and response evaluations.

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Funding

Competing interests

I.M. has received research grants from Alligator, Bioncotech, Bristol Myers Squibb (BMS), Leadartis, Pfizer and Roche; has received speaker’s bureau honoraria from MSD; and is a consultant or advisory board member for Alligator, AstraZeneca, Bayer, Bioncotech, BMS, F-Star, Genmab, Gossamer, Merck Serono, Numab, Pieris and Roche. E.C. is a consultant or advisory board member for AstraZeneca, Beigene, BMS, MSD and Roche. S.C. has received honoraria from Amgen, AstraZeneca, BMS, Janssen, Merck, MSD, Novartis and Roche; is an advisory board member for Amgen and AstraZeneca; has received funding for travel and conference attendance from AstraZeneca, MSD and Roche; and has received research grants from AstraZeneca, BMS, Boehringer Ingelheim, Janssen-Cilag, Merck, Novartis, Onxeo, Pfizer, Roche and Sanofi, and non-financial research support (investigational drugs) from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Medimmune, Merck, NH TherAGuiX, Onxeo, Pfizer and Roche. S.C. has been a principal investigator of academic or industry-sponsored clinical trials of intratumoural immunotherapies for Abbvie, AstraZeneca/Medimmune, BMS, Eisai/H3 Biomedicine, IDERA, Lytix Biopharma, MSD, Nanobiotix and Sanofi/BioNTech. A.M. has been a principal investigator of academic or industry-sponsored clinical trials of intratumoural immunotherapies from AstraZeneca, BMS, Eisai, IDERA, Lytix Biopharma, Merck/MSD, Roche and Transgene; is a member of the Data Safety and Monitoring Board of a trial of a intratumoural TLR3 agonist sponsored by Oncovir (NCT02423863); and has participated in scientific advisory boards or has provided consultancy services on the topic of intratumoural immunotherapies for Amgen, AstraZeneca, Banque Pour l’Investissement, Bayer, Eisai, eTheRNA, Lytix Biopharma, Medincell, MSD, Novartis, Oncosec, Pillar Partners, Rigontec and Sanofi/BioNTech. M.A. declares no competing interests.
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