AACR Immune Cell Therapies: Early Study Results Suggest Activity of Multiantigen T-Cell Therapy in Patients With Pancreatic Cancer
Findings from a small phase I study investigating a nonengineered, multiantigen-specific T-cell therapy for the treatment of pancreatic cancer has found that the therapy had clinical activity and was safe and well tolerated. The early results suggest that the immune cell therapy may provide a feasible approach to treating this cancer. The study by Smaglo et al was presented at the AACR conference on Immune Cell Therapies for Cancer: Successes and Challenges of CAR T Cells and Other Forms of Adoptive Therapy (Abstract PRO1/Poster A18).
Although pancreatic cancer is rare, accounting for about 3% of all cancers in the United States, it is among the deadliest, with 5-year survival rates hovering at just 9.3%. According to the National Cancer Institute, this year, an estimated 56,770 people will be diagnosed with pancreatic cancer and nearly 46,000 will die from the disease.
Study Methods
Eighteen patients with pancreatic adenocarcinoma were treated with up to six infusions of customized, nonengineered, multiantigen-specific T cells in a three-arm phase I study. Arm A of the study included nine patients with unresectable or metastatic pancreatic cancer who were responding to standard first-line chemotherapy, arm B included six patients with progressive disease or intolerance to first-line therapy, and arm C included three patients with potentially resectable disease.
The researchers created each patient’s customized treatment after harvesting immune cells from their blood and developing a nonengineered T-cell therapy with single T-cell lines that targeted the tumor-associated antigens PRAME, SSX2, MAGEA4, NY-ESO-1, and Survivin. The patients’ T cells were expanded in number in the laboratory and infused back into the patients.
Results
Of the nine patients in arm A who received cells in conjunction with first-line chemotherapy, two are at a point in treatment too early to evaluate; two had disease progression; and five have had ongoing radiographic stable disease or responses of 6- to 9-month duration, including one complete response. Of the six patients treated with progressive disease—arm B—three continued to have progression on treatment, and three have ongoing stable disease (1–6 months duration). In arm C, the three patients with potentially resectable disease received one infusion of T cells preoperatively and are still receiving their postoperative infusions and adjuvant therapy.
Clinical benefit has correlated with the detection of tumor-reactive T cells in patients’ peripheral blood and within tumor biopsy samples (arm C) postinfusion. According to the study findings, T cells have exhibited activity against targeted antigens as well as nontargeted tumor-associated antigens, including MAGEA2B and AFP, indicating induction of antigen/epitope spreading. None of the patients experienced infusion-related systemic toxicity or neurotoxicity.
Potential Clinical Benefit
“Pancreatic adenocarcinoma is extremely hard to treat. Most patients [are treated with] intense chemotherapy, which often has severe adverse effects, and we urgently need alternative approaches to treatment,” said lead study author Brandon G. Smaglo, MD, FACP, Assistant Professor of Internal Medicine and Medical Director of Hematology/Oncology at Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, in a statement. “We are encouraged by the early results suggesting that the T-cell therapy we are testing is a feasible approach to pancreatic adenocarcinoma treatment that is tolerable and shows signs of clinical activity. We look forward to treating more patients and continuing to follow those whose responses are ongoing.”
Disclosure: Funding for this study was provided by V Foundation and the Pancreatic Cancer Action Network. For full disclosures of the study authors, visit aacr.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
