Novel T-Cell Therapies Yield Decade-Long Remission in Epithelial Cancer

Findings from 2 studies showed that onetime cell therapies can elicit complete tumor regression in patients with advanced epithelial cancers.

Novel T-cell therapies may be able to achieve long-lasting remission and complete tumor regression in patients with advanced epithelial cancers, as was shown in 2 human papillomavirus (HPV)–related studies shared at the 2025 Society for Immunotherapy of Cancer Annual Meeting in National Harbor, Maryland.1,2

Both studies were presented by Christian Hinrichs, MD, codirector of the Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence and chief of the Section of Cancer Immunotherapy at Rutgers Cancer Institute in New Brunswick, New Jersey. The first presentation, titled “Complete Tumor Regression of Metastatic Epithelial Cancer Following T Cell Receptor (TCR)-T Cell Therapy,” reported interim results from a phase 2 trial evaluating TCR-T cells targeting the HPV16 E7 oncoprotein in patients with metastatic HPV-associated cancers. The second presentation, titled “Decade-Long Epithelial Cancer Remissions From Cellular Therapy,” shared data of 2 patients with metastatic cervical cancer who remained in remission for 10 years after receiving a single infusion of tumor-infiltrating lymphocyte (TIL) therapy.

“These studies indicate that onetime cell therapies can achieve durable responses in epithelial cancers, which historically have been more resistant to these treatments than blood cancers,” said Hinrichs in a press release on the findings.3 “The decade-long complete responses to TIL therapy give hope that these patients may be cured. The E7 T-cell results that include complete responses are encouraging and support continued study of the approach.”

The First Presentation

This presentation shared data from the first 10 patients of 20 planned patients in a single-center phase 2 trial (NCT05686226) at Rutgers Cancer Institute. Eligible patients had recurrent/refractory or metastatic HPV-mediated cancers with any primary tumor site who had received first-line therapy. They also had HPV-16–positive tumors and the human leukocyte antigen HLA-A*02:01 allele.

Of the 10 patients, 6 experienced a response; the response was a partial response in 4 patients, of whom the cancer types were head and neck cancer (n = 2) and cervical cancer (n = 2). A complete response (CR) occurred in 2 patients, of whom one patient with esophageal cancer had an ongoing CR for 11 months (patient 6) and the other patient with anal cancer had an ongoing CR of 12 months (patient 7). One patient with head and neck cancer had progressive disease, and a total of 3 patients had stable disease, of whom 2 had head and neck cancer and 1 had anal cancer.

The presentation analyzed both patients who experienced a CR.

Patient 6 was a 49-year-old woman with metastatic HPV-16–positive esophageal cancer who received prior treatment consisting of carboplatin plus paclitaxel and radiation, carboplatin plus paclitaxel and pembrolizumab (Keytruda), and pembrolizumab alone.

As of the analysis, the patient had no evidence of disease via PET scan and NavDx at 11 months after a single treatment.

Patient 7 was a 60-year-old woman with metastatic anal cancer who received prior treatment consisting of carboplatin plus paclitaxel, nivolumab (Opdivo), and chemotherapy plus nivolumab maintenance. As of the analysis, the patient had no evidence of cancer via PET scan and NavDx at 12 months after treatment.

Hinrichs added, “We found that E7-directed T cells can induce meaningful and sometimes complete responses in patients with limited options. It's an encouraging step toward effective engineered T-cell therapies for these and other epithelial cancers.”3

Treatment consisted of E7 TCR-T cells at 5 x 1010 cells, with conditioning consisting of cyclophosphamide at 30 mg/kg twice and fludarabine at 25 mg/m2 5 times as well as adjuvant therapy of aldesleukin (Proleukin) at 720,000 IU/kg for up to 6 doses.

The primary end point of the trial was the objective response rate per RECIST v1.1.

Notably, the main changes from phase 1 of the trial were the use of a rapid manufacturing process with a vein-to-vein time of 14 to 16 days and the exclusion of patients with HLA-A*02:01 allele loss when feasible.

Maria, a patient from Philadelphia, Pennsylvania, said, “When I finished my treatment, I couldn't believe how quickly I started feeling better. Within a month, the nodules were gone, and for the first time in years, I felt free, full of energy, and living the life. I can spend time with my son, do the things I love, and really enjoy life again.”3

The Second Presentation

This presentation examined 2 patients with metastatic cervical cancer who remain in CR for 10 years following a single infusion of TIL therapy in a phase 2 trial (NCT01585428).

Of the 2 patients, one each had cervical squamous cell carcinoma and cervical adenocarcinoma. Per circulating tumor DNA (ctDNA) analysis and imaging, the levels of ctDNA and tumor progression have been undetectable for 10 years in both patients.

Regarding the T-cell responses, there was an observed and defined expansion and contraction of antitumor T cells sufficient for ongoing tumor response.

In the patient with cervical squamous cell carcinoma, tumor architecture-resolved mapping revealed that the TIL predominantly targeted subclonal neoantigens. Strongly targeted neoantigens included SETDB1 E21D and METTL17 E279K.

Additionally, the tumor alterations observed in immune-resistance genes were partial and focal.

The key questions that were explored in this analysis were:

1. How durable are the tumor responses?
2. Is ongoing T-cell persistence required for ongoing tumor response?
3. What were the primary tumor regression antigens?
4. What is the profile of tumor-intrinsic immune-resistance gene defects?

Sue, a patient with an ongoing CR in Washington, DC, said, “When I joined the study, my cancer was very advanced, and I wanted to use whatever time I had left to help enhance research that could benefit others. I never imagined the treatment would work for me, but just 2 months after receiving my TIL infusion, my cancer was undetectable on the scans. Now, 12 years later, I'm still cancer free and deeply grateful to the doctors and researchers who made that possible.”3

Disclaimers: Hinrichs reported principal investigator research grant from Neogene Therapeutics, Iovance Biotherapeutics (in-kind support), and Naveris (in-kind support); consultant roles at Vir Biotechnology; owner, shareholder, and founder roles at Scarlet TCR; scientific/medical advisory board member roles for Neogene Therapeutics and Capstan Therapeutics; and being a patent inventor for patents related to immunotherapy and cell therapy including E6 TCR, E7 TCR, HPV-TIL, and tethered IL-15/IL-21.

References

1. Norberg SM, Doran SL, Cao J, et al. Complete tumor regression of metastatic epithelial cancer following T cell receptor (TCR)-T cell therapy. Abstract presented at: 2025 Society for Immunotherapy of Cancer Annual Meeting; November 5-9, 2025; National Harbor, MD. Abstract 366.
2. Norberg SM, Biswas A, Krishnamurthy S, et al. Decade-long epithelial cancer remissions from cellular therapy. Abstract presented at: 2025 Society for Immunotherapy of Cancer Annual Meeting; November 5-9, 2025; National Harbor, MD. Abstract 377.
3. Landmark data from Rutgers Cancer Institute and RWJBarnabas Health show long-term complete responses of T cell therapies for HPV-related cancers. News release. Rutgers Cancer Institute. November 10, 2025. Accessed November 11, 2025. https://tinyurl.com/4628ccs3