Local drug delivery of immunotherapy in head and neck cancer: a narrative review
Year: 2026
Type: review
Abstract: Background and Objective: There are several immunotherapies approved by the U.S. Food and Drug Administration, but the response rate is relatively low and systemic administration of the immunotherapy may cause serious side effects. Local drug delivery of immunotherapy in head and neck cancer is promising because the therapeutic agents are distributed directly to the tumor site, therefore avoiding systemic toxicity. This narrative review aims to provide an overview of both clinical and preclinical research on local immunotherapy in head and neck cancer. It seeks to identify promising directions for future preclinical investigations, to explore which preclinical findings have the potential for clinical translation, and to identify clinical trial results that demonstrate potential for broader application as new standards of care. Methods: A review of the papers and clinical trials published between January 1st, 1960 and October 8th, 2025, was conducted by querying the MEDLINE database via PubMed, as well as ClinicalTrials.gov. Key Content and Findings: There are preclinical and clinical studies testing various strategies for local drug delivery of immunotherapy in head and neck cancer. The related agents for immunotherapy are cytokines, chemokines, interferons, toll-like receptor agonists, antibodies, peptides, immune cells, plasmids, and chemical drugs. Hydrogels and microneedles have been developed to increase the retention time in the tumor site. While all subtypes of head and neck cancer have potential for benefit from local drug delivery strategies, current clinical translation is focused on those subsites that are easily accessible, such as the oral cavity, cutaneous and mucosal melanoma. Conclusions: Local drug delivery of immunotherapy for the treatment of head and neck cancer is a promising approach to enhance anti-cancer immunity and limit side effects associated with systemic administration by delivering multiple therapeutic agents.
DOI: 10.21037/fomm-25-13
Authors: Jing Nie, Richard Bryan Bell, Di Wen
Institution: Oregon Health & Science University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7135222737