Multi-antigen T cell therapy shows early promise in pancreatic cancer trial

A first-in-human study has shown that an autologous, multi-antigen T cell immunotherapy achieved durable disease control in selected patients with pancreatic cancer, with a favourable safety profile and evidence of sustained immune activity

A recent paper has described a novel immunotherapy approach for pancreatic cancer that has shown encouraging early clinical signals in a first-in-human phase 1/2 study. The trial – known as TACTOPS – has evaluated the safety, feasibility and preliminary efficacy of an autologous T cell therapy designed to target multiple tumour-associated antigens in patients with pancreatic ductal adenocarcinoma, a disease that has remained largely resistant to existing immune-based treatments.

The study was a collaboration between investigators at Baylor College of Medicine, the Dan L Duncan Comprehensive Cancer Center, the Center for Cell and Gene Therapy, Texas Children’s Hospital and Houston Methodist Hospital, all of Houston, Texas, USA. Together, the team sought to address the biological heterogeneity of pancreatic cancer by directing the immune response against a panel of five tumour-associated antigens rather than a single molecular target.

“We wanted to develop a targeted therapeutic that would hone the immune system on tumour-associated antigens that were present on malignant cells. We targeted five different antigens to deal with the polyclonal nature of the disease,” said Dr. Ann Leen, professor of paediatrics, haematology and oncology at the Center for Cell and Gene Therapy, who served as a co-corresponding author on the study.

The investigators enrolled patients into three distinct cohorts that reflected different clinical stages of disease. Arm A included patients with advanced pancreatic cancer who had demonstrated a response to first-line chemotherapy. Arm B comprised patients with metastatic disease whose cancer had progressed despite first-line chemotherapy. Arm C included patients with surgically resectable disease who underwent tumour removal. Each participant provided a blood sample from which personalised T cell products were manufactured under good manufacturing practice conditions at the Center for Cell and Gene Therapy. In total, 37 patients received six monthly infusions of their individualised T cell therapy.

Clinical outcomes varied substantially across the cohorts. Patients in Arm A and Arm C experienced the most favourable responses. Among patients with advanced disease who had responded to frontline chemotherapy, investigators reported an 84.6 per cent disease control rate. In the surgically resected cohort, two of nine patients remained disease-free more than five years after surgery, an outcome that remains uncommon in pancreatic cancer. By contrast, patients in Arm B, whose disease had proven refractory to standard treatment, achieved a disease control rate of only 25 per cent.

Importantly, the therapy demonstrated a strong safety profile across all cohorts. Only one serious adverse event was considered possibly related to treatment, and no dose-limiting toxicities were observed. This tolerability stands in contrast to several earlier cellular immunotherapy strategies, which have encountered safety barriers in solid tumours.

“Pancreatic cancer does not appear as foreign to the immune system as [with] many other cancers. This novel immunotherapy may help the immune system to recognise and attack cancer cells in a way that other immunotherapies have not achieved thus far,” said Dr. Benjamin Musher, professor of medicine at Baylor College of Medicine and medical director of medical oncology at the Dan L Duncan Comprehensive Cancer Center, who also served as a co-corresponding author.

Correlative laboratory analyses supported the observed clinical effects. Positive outcomes were associated with functional expansion of infused T cells and their sustained persistence in peripheral blood samples collected during treatment when compared with baseline specimens. These findings have suggested that the transferred cells not only survived in patients but retained anti-tumour activity over time.

The research team has already begun to use the trial data to refine the therapeutic strategy in preparation for subsequent studies. Planned future trials may evaluate the T cell therapy as a standalone intervention or in combination with other immune-modulating approaches, with the aim to enhance efficacy further and extend benefit to a broader patient population.

“Nationwide, only five per cent of pancreatic cancer patients enrol in clinical trials,” said Musher.

“To improve pancreatic cancer outcomes meaningfully, we must explore all possible treatment options and enrol more patients in clinical trials.

“Studies such as ours, which include robust correlative science, allow us to learn from both successes and failures and to facilitate further advances.

“They also provide patients with much-needed hope while allowing them to feel part of something larger than themselves,” Professor Musher added.

While larger, randomised studies will be required to define clinical benefit conclusively, the TACTOPS trial has provided early evidence that multi-antigen autologous T cell therapy can prove safe, biologically active and potentially transformative in a cancer type that has long resisted immunotherapeutic intervention.

“The clinical and translational science expertise at Baylor within the Duncan Cancer Center and the Center for Cell and Gene Therapy enables our team to conduct complex trials that reach patients at different stages of disease.

“We could not achieve this without close collaboration between laboratory and clinic, the work of our regulatory team and access to a top-tier good manufacturing practice facility,” Leen said.

For further reading please visit: 10.1038/s41591-025-04043-5