Next-Gen TCR-T Cell Therapy Produces Strong Responses in HPV-Associated Cancers

In an interview with Targeted Oncology^®, Christian S. Hinrichs, MD, co-director of the Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute, provides a brief overview of an ongoing phase 2 study (NCT05686226) assessing the clinical activity of immunotherapy with T cell receptor (TCR)-T cells in patients with various metastatic human papillomavirus (HPV)-associated cancers. Initial findings of this study were recently presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting press conference.

Watch the first part of Dr Hinrichs’ interview.

The second study presented at the SITC meeting focuses on a “next-generation” approach following TIL therapy, utilizing autologous peripheral blood T cells that are genetically engineered with a specific receptor. Engineering these cells enables a more targeted approach to the cancer.

Unlike typical CAR T therapies, which generally target antigens on the cell surface, this method employs a TCR, which is designed to target an intracellular antigen that is processed and recognized by the T cell. The specific target protein is HPV16 E7.

This study is enrolling patients with HPV-associated cancers of any primary tumor site after first-line therapy, with a planned total enrollment of 20 patients. To date, 6 of the 10 patients treated so far have shown promising objective responses (partial or complete response per RECIST criteria). Crucially, 2 complete responses were documented in patients who had metastatic disease which was refractory to prior lines of therapy. These responses are currently ongoing—one at 12 months and the other at 14 months post-treatment.

Overall, these results demonstrate the potential of targeted, engineered TCR therapies to produce significant clinical benefits even in heavily pretreated, refractory solid tumors.

Read the full interview here.