Non-Engineered T-Cells May Be Clinically Meaningful For Pancreatic Cancer

Jul 20, 2019 | Multiantigen-Specific T-cell Therapy, Pancreatic Cancer

Guangzhou Institutes of Biomedicine Breakthrough as they Produce Stem Cell-Originated T Cells

A Phase 1 clinical trial evidence meaningful data points as more than half of pancreatic adenocarcinoma patients showed positive clinical responses when treated with an investigational multiantigen-specific T-cell therapy.

What is the Investigational Therapy?

“The nonengineered T-cell therapy used immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes that simultaneously target the TAAs PRAME, SSX2, MAGEA4, NY-ESO-1, and Survivin,” reports Healio Hemonc Today.

The Study

The study included three treatment arms in which investigators evaluated the safety and feasibility of multiTAA T cells as well as progression-free and overall survival.

  • Arm A-includes patients with unresectable or metastatic pancreatic adenocarcinoma whose disease responded to first-line chemotherapy
  • Arm B- comprised of patients with the progressive refractory disease after first-line chemotherapy
  • Arm C-included patients with potentially resectable disease

The investigators generated 35 clinical-grade mutliTAA T cell lines that included CD3+ T cells (mean 97.2 +/- 1.3%) with mix of CD4+ (mean 47.2 +/- 7.4%) and CD8+ (mean 39.5 +/- 6.4%) T cells that recognize the antigens PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin.

Cell Manufacturing Process

The cell manufacturing process takes 4 to 6 weeks and patients will receive six doses of the cells which are all manufactured in a single run.

Clinical Investigator Comments

Brandon G. Smaglo, MD, FACP, an assistant professor of internal medicine and oncology at Baylor College of Medicine’s Dan L. Duncan Comprehensive Cancer Center and study co-author told journal Cell that “there is a dire need for better systemic therapies in all stages of pancreatic cancer, and there is a need for the systemic therapies to be better tolerated than the current standards of two to three chemotherapy drug combination regimens.” Dr. Smaglo continued “Our approach is novel because, unlike CAR T-cell approach, the T cells we are using are nonengineered. They are cultured in a mixture with the antigens we intend for them to target so that they can naturally acquire these features.” He continued “It is important that potential patients be identified early so that when the T cells are needed for use, they are ready.”

Pancreatic Cancer

Rare cancer—about 3% of all cancers in the United States—but one of the deadliest, with 5-year survival rates hovering at just 9.3%. According to the National Cancer Institute, an estimated 56,770 will be diagnosed with pancreatic cancer and nearly 46,000 will die from the disease.

Funding

Funding for the clinical research provided by the V Foundation and the Pancreatic Cancer Network

Key Takeaway Points

Infusions of nonengineered, multiantigen-specific T-cell therapy appeared to be safe and tolerable for patients with pancreatic cancer

No patient in the study experienced infusion-related systemic toxicity or neurotoxicity

Lead Research/Investigator

Brandon G. Smaglo, MD, FACP

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