Novel immunotherapy against pancreatic cancer shows promising results in phase 1/2 study

Novel immunotherapy against pancreatic cancer shows promising results in phase 1/2 study

A recent publication inNatural medicinedescribes a novel immunotherapy for pancreatic cancer that has shown promising results in an initial phase 1/2 human trial. The TACTOPS study, which examined the safety and clinical effects of autologous T cell therapy against multiple tumor antigens, was a collaboration between researchers at Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Center for Cell and Gene Therapy, Texas Children's Hospital and Houston Methodist Hospital.

We wanted to develop a targeted therapeutic that would prime the immune system for tumor-associated antigens (TAAs) present on malignant cells. We targeted five different antigens to deal with the polyclonal nature of the disease.”

Dr. Ann Leen, co-author, Professor of Pediatrics - Hematology and Oncology at the Center for Cell and Gene Therapy

"Pancreatic cancer does not look as alien to the immune system as other cancers. This novel immunotherapy may help the immune system recognize and attack cancer cells in ways that other immunotherapies have not been able to do," said co-author Dr. Benjamin Musher, professor of medicine at Baylor and medical director of medical oncology at the Dan L Duncan Comprehensive Cancer Center.

Patients with pancreatic cancer were included in one of three study cohorts. Arm A included patients with advanced disease who responded to first-line chemotherapy. Arm B included patients with metastatic disease who had progressed on first-line chemotherapy. Arm C included patients with surgically resectable disease. Each patient provided a blood sample and an individual T-cell therapy was prepared at the Center for Cell and Gene Therapy. A total of 37 study participants received six monthly infusions of T cells.

Patients in Arms A and C showed promising results, with a disease control rate of 84.6% in the group of patients who responded to first-line chemotherapy (Arm A). Two of nine patients who underwent surgical resection (Arm C) remained disease-free more than five years after surgery. Researchers observed only 25% disease control in patients with refractory disease (Arm B). The therapy was extremely well tolerated, with only one potentially treatment-related serious adverse event documented in all three cohorts.

Positive clinical outcomes correlated with functional T cell expansion and persistence of infused cells in blood samples collected during therapy compared to those collected at baseline. Researchers are already using data from this study to refine their approach in preparation for the next trial, which may include T cell therapy alone or in combination with other immunotherapies.

“Nationwide, only 5% of pancreatic cancer patients participate in clinical trials,” Musher said. "To meaningfully improve outcomes in pancreatic cancer, we need to explore all possible treatment options and enroll more patients in clinical trials. Studies like ours, which incorporate robust correlative science, help us learn from successes and failures and enable further progress. They also give patients much-needed hope while helping them feel part of something bigger than themselves."

“Baylor's clinical and translational science expertise in the Duncan Cancer Center and the Center for Cell and Gene Therapy allows our team to conduct complex studies that reach patients at various stages of disease,” Leen said. “We could not achieve this without close collaboration between laboratory and clinic, the excellent work of our regulatory team and a world-class GMP (Good Manufacturing Practices) facility.”

Dr. Spyridoula Vasileiou and Brandon G. Smaglo, along with Musher, are the first authors of this work. Other contributors include Catherine S. Robertson, Mengfen Wu, Tao Wang, Ayumi Watanabe, Manik Kuvalekar, Yovana Velazquez, Shamika Ketkar, Tamadar Al Doheyan, Penelope G. Papayanni, Aakash Shah, Natalia Lapteva, Bambi J. Grilley, George Van Buren, Premal D. Lulla, Helen E. Heslop, Cliona M. Rooney and Malcolm K. Brenner. All authors were affiliated with Baylor College of Medicine, the Center for Cell and Gene Therapy, the Dan L Duncan Comprehensive Cancer Center, Texas Children's Hospital, and/or Houston Methodist Hospital at the time of conducting the study. A full list of funding sources can be found in the publication.

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