Medpage Today article-
Nonengineered T-Cells Active in Pancreatic Cancer
Simultaneous targeting of multiple tumor antigens, potential for reduced toxicity
by Charles Bankhead, Senior Editor, MedPage Today
July 19, 2019
Six of seven patients with inoperable or metastatic pancreatic cancer had objective responses or stable disease when treated with their own nonengineered T-cells plus chemotherapy, investigators reported.
One patient had a complete response, two had partial responses, and three had stable disease for more than 6 months. One other patient treated only with T-cell infusions also had stable disease for more than 6 months.
Although the study was limited to patients with pancreatic cancer, other types of solid tumors might be amenable to the treatment, Brandon Smaglo, MD, of Baylor College of Medicine in Houston, reported at the Immune Cell Therapies for Cancer (ICTC) conference in San Francisco.
"Recognizing that we've treated a small number of patients so far, these are still some things that are exciting to see and encourage us to look into this therapy further as we move forward," said Smaglo.
In contrast to chimeric antigen receptor (CAR) T-cell therapy, cells harvested from the cancer patients were not genetically modified to target a specific tumor-associated protein. Instead, researchers developed the therapy from single T cell lines that simultaneously target five tumor-associated antigens (TAAs): PRAME, SSX2, MAGEA4, NY-ESO-1, and Survivin. Targeting multiple TAAs should reduce the odds that tumor cells can evade immune response, said Smaglo.
The autologous T cells (a combination of CD3+, CD4+, and CD8+ T cells) were expanded in a culture that included a mix of peptides from the targeted TAAs. The cells were then infused back into the patients, who have received as many as six infusions.
"The product we're generating is a cultured version of their T cells, having only been modified the way they normally would by being exposed to something foreign," Smaglo told MedPage Today. "As a result, we're able to grow them up in a number of different targets at once, which hopefully will cover our bases more completely within the tumor and address some of the tumor heterogeneity. We end up with a product that is intended to be better tolerated because it is autologous, reducing the chances of some sort of a reaction against it."
To date, Smaglo and colleagues have generated 35 clinical-grade multi-TAA T cell lines, and they have treated 18 patients with pancreatic cancer: nine with disease that was responding to initial treatment with chemotherapy; six who had disease that progressed during or after chemotherapy; and three who had resectable cancer.
The nine patients responding to chemotherapy received the T-cell infusions along with chemotherapy. The six patients with progressive disease received only the T-cell infusions, and the three patients who underwent surgery received one infusion before surgery and additional infusions after surgery.
Seven of the nine-patient subgroup were evaluable for response, which demonstrated clinical benefit (response plus stable disease) in all but one patient. One of the six patients with progressive disease had ongoing disease stabilization at 6 months, and two others had symptom stabilization. The three patients with resectable disease received the preoperative T-cell infusion and remain in follow-up as they receive postoperative infusions.
Clinical benefit correlated with the detection of post-infusion tumor-reactive T cells in blood samples and tumor specimens. Smaglo reported that the T cells have demonstrated activity against the five targeted TAAs, as well as several non-targeted antigens.
Thus far, no patient has exhibited signs of treatment-related systemic or neurologic toxicity.
Beyond continuation of the current study, Smaglo said investigators have identified other potential areas of investigation: the feasibility of using the therapy as maintenance to give patients a break from chemotherapy and whether postoperative T-cell infusion reduces the rate of recurrence.
Sponsored by the American Association for Cancer Research, the ICTC continues through Monday, July 22.
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