Scientists at The University of Texas MD Anderson Cancer Center have immunomodulated a robust and selective cancer-causing T cell receptor to cure pancreatic cancer with fewer side effects than current widely available immunotherapies.

The study is published in Cell Reports.

The research represents a significant advancement in the therapy of a lethal cancer.

“If the trial results are replicated, this approach could be the basis for a new and effective combination therapeutic approach to beating pancreatic cancer,” said Alok Sharma, Ph.D., Director of Research at MD Anderson.

The team created four unique T cell receptors and hundreds of genetically engineered human cancer-fighting human cells, which were immunologically targeted with mast cells – a type of chemo- and radiation-resistant skin cancer remnant.

Eligible cells were bred in a transgenic manner that could not be detected with conventional cancer markers.

During the trial, ten of the 10 tumor-transplanted patients experienced drug resistant disease progression and double-negative cancer. Two patients developed relapsed tumors and two had dramatic regression of tumor cells.

Study results are encouraging because the treated patients achieved a median survival of 18 months, which is significantly higher than a recent report.

“Having a tumor suppressor present can impede the immune system abuse that can make pancreatic tumor more aggressive and more likely to recur,” Sharma said.

“Patients treated with immune checkpoint inhibitors whose tumors responded more strongly demonstrated improved outcomes and were free of long-term side effects such as skin cancer,” he said. “This approach involved activating two key immune checkpoint inhibitors to treat drug-sensitive multiple pancreatic cancer cells that were hardened by the radiation and chemotherapy.”

One of the anti-PD-L1 inhibitors is Zexen, which is FDA-approved to treat several cancers. One inhibitor was developed by MD Anderson biochemist Dr. Vinay Gupta, Ph.D., in collaboration with Dr. Yang-Shih Sung, Ph.D., in India.

“Zexen, though not FDA-approved for patients due to clinical disadvantage, proved highly effective in blocking inflammation, inducing apoptosis and increasing survival in a panel of primary human pancreatic cancer models and in animal models of multiple sclerosis, oral squamous cell carcinoma and basal cell carcinoma,” said Sharma.

“Zexen showed a higher rate of complete tumor elimination and comparable safety when used in combination with immunotherapy,” he said. “This genotype mouse model is particularly useful because it reproduces malignant features of human pancreatic cancer, but demonstrates the present translational potential to modulate favorable tumor microenvironment for better outcome.”