T cell therapies show long-term HPV gains: A Breakthrough in Cancer Treatment
A groundbreaking study conducted by researchers at Rutgers Cancer Institute, New Jersey's premier National Cancer Institute (NCI)-designated Comprehensive Cancer Center, and RWJBarnabas Health, in collaboration with the National Cancer Institute, has revealed the remarkable potential of novel T cell therapies in achieving long-lasting remission and complete tumor regression in patients with advanced epithelial cancers. The findings, presented by Dr. Christian Hinrichs at the Society for Immunotherapy of Cancer (SITC 2025) Annual Meeting, offer a glimmer of hope for patients with limited treatment options.
The study focused on two HPV-related research projects. In the first, researchers evaluated genetically engineered T cell receptor (TCR)-T cells designed to target the HPV16 E7 oncoprotein (E7 T cells) in patients with metastatic HPV-associated cancers. The treatment involved a conditioning regimen, a single infusion of up to 50 billion E7 T cells, and a median of three doses of adjuvant aldesleukin. All 10 patients had advanced cancers, with five suffering from head and neck cancer, two from cervical cancer, two from anal cancer, and one from esophageal cancer. The treatment was well-tolerated, with side effects consistent with the preparative regimen and aldesleukin.
The results were impressive, with six out of 10 patients achieving substantial tumor shrinkage. Two patients experienced complete tumor regression, which has persisted for 11 and 12 months, respectively. These patients had previously received immunotherapy and other standard treatments, making the findings even more significant. Dr. Hinrichs emphasized the difficulty of treating metastatic HPV-associated cancers and expressed optimism about the potential of E7-directed T cells to induce meaningful and sometimes complete responses in patients with limited options.
The second study revealed an extraordinary finding: two patients with metastatic cervical cancer remain in complete remission 10 years after receiving a single infusion of tumor-infiltrating lymphocyte (TIL) therapy. This study, conducted as part of clinical trial NCT01585428, provides the strongest evidence to date that cellular therapy can produce long-term, potentially curative responses in epithelial cancers, the most common type of malignancy. A decade after treatment, patients exhibited no evidence of disease based on imaging and circulating tumor DNA analysis. The anti-tumor T cells underwent a temporary expansion phase that coincided with tumor shrinkage and apparent elimination, suggesting that the tumors were cleared during the initial response.
The study's success is attributed to the collaboration between the National Cancer Institute and Rutgers Cancer Institute, with the phase II study conducted at Rutgers Cancer Institute. The cell products for the study were manufactured in a Good Manufacturing Practices (GMP) facility on-site at Rutgers Cancer Institute, part of the Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence. This center is uniquely positioned to advance novel cell therapies through specialized research capabilities and GMP infrastructure, supporting both innovative clinical trials and the translation of laboratory discoveries into patient care.
The patients' experiences highlight the profound impact of these therapies. Maria, a patient from Philadelphia, shared her story, expressing her gratitude for the team's research and the positive changes it brought to her life. Sue, a patient from Washington, DC, who has had an ongoing complete response, described her motivation to participate in the clinical trial, emphasizing the potential to enhance research that could benefit others. These personal accounts underscore the importance of continued research and the potential for these therapies to transform lives.
Dr. Hinrichs concluded that these studies indicate one-time cell therapies can achieve durable responses in epithelial cancers, which have historically been more resistant to these treatments than blood cancers. The decade-long complete responses to TIL therapy offer hope that these patients may be cured. The E7 T cell results, including complete responses, are encouraging and support the continued study of this approach. The findings emphasize the significance of conducting research at an NCI-designated Comprehensive Cancer Center and the collaborative efforts required to translate laboratory discoveries into clinical trials and ultimately into life-changing treatments for patients.
