Immunotherapy Shows Promise in Pancreatic Cancer

Treating patients with their own nonengineered T cells may be promising in pancreatic cancer, based on preliminary results presented at the American Association for Cancer Research special conference on Immune Cell Therapies for Cancer in San Francisco, CA. In an ongoing phase I feasibility trial, the multiantigen-specific T-cell therapy seemed safe and generated responses in several patients.

Based on the success of multiantigen-specific T-cell therapy in treating other cancers such as leukemia, Brandon Smaglo, MD, of Baylor College of Medicine in Waco, TX, and his team decided to test the approach in pancreatic cancer. The researchers extracted patients' T cells and then cultured and expanded them in the lab. The cells were cultured with dendritic cells loaded with five peptides from antigens expressed in pancreatic cancer cells—Survivin, SSX2, NY-ESO-1, MAGE-A4, and PRAME. The mixture was then infused into patients, where it is thought that the T cells recognize tumor-associated antigens and kill cancer cells.

The researchers tested the therapy in 18 patients with pancreatic cancer: nine with inoperable or metastatic disease responding to chemotherapy; six with advanced cancer whose disease progressed despite chemotherapy or who were intolerant to it; and three with surgically removed tumors who received one infusion prior to surgery and additional infusions afterward.

One patient who received the T cells with chemotherapy had a complete response, two had partial responses, and four had stable disease; five of the seven had responses or stable disease lasting at least 6 months. Additionally, one patient with disease progression experienced stable disease for more than 6 months, and two of three patients with operable disease continued T-cell infusions and adjuvant therapy for at least 5 months postoperatively. None of the patients experienced treatment-related side effects. Patient responses were associated with a greater number of circulating T cells that home to the specified antigens, as well as other antigens.

“It's definitely something that is very tolerable and is very exciting as an additive to what's already standard of care,” Smaglo says. Upon completing the trial, he and his team plan to conduct a larger trial testing the multiantigen-specific T-cell therapy plus chemotherapy as a first-line treatment.

“The authors have shown that this appears to be a safe therapeutic approach,” says Diane Simeone, MD, of NYU Langone Health in New York, NY, who is not involved in the research. However, because most patients received the multiantigen-specific T-cell infusions with chemotherapy, parsing their responses is difficult. “The signal from the therapy looks interesting, but I think further work would need to be done to see if the therapy has a clinical impact that extends beyond the chemotherapy backbone,” she says.

For Gregory Beatty, MD, PhD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, who is also not connected to the trial, the research demonstrates that multiantigen-specific T-cell therapy is feasible in pancreatic cancer. He hopes the researchers will investigate the biological underpinnings of the therapy, including if and how the infused T cells interact with tumor cells. “They showed that T cells could be detected in tumors, but presence doesn't mean they are active against the cancer,” Beatty says.

Beatty adds that the therapy may have even more potential as a model for studying immune-based therapies: “This is now a way for us to learn about what it takes for the immune system to actually attack pancreatic cancer, and so I think that's equally as important for the field, because then it opens up new ideas and hopefully novel treatment strategies.” –Catherine Caruso

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