OCRA-Funded Research Helps Immune System Better Attack a Known Therapeutic Target

Snap summary: OCRA-funded researchers set out to improve immune response against a known therapeutic target, and provided a glimpse into a world where an ovarian cancer patient’s own immune system can be harnessed to treat and eradicate the disease.

Researchers at Roswell Park Comprehensive Cancer Center have made significant gains toward immunotherapy as a viable treatment option for ovarian cancer patients. OCRA grantee Dr. Bob McGray, and OCRA grantee and SAC member Dr. Kunle Odunsi, were co-authors on the study. The results of their exciting OCRA-funded research were published in the Journal for ImmunoTherapy of Cancer.

In this study, the team set out to improve immune response against a known therapeutic target: folate receptor alpha (FRα), which is a protein found in excess in many ovarian cancers. 

They equipped T-cells — a crucial part of the immune system — to better recognize and fight the targeted cells using a process called adoptive T-cell transfer (ACT). ACT involves modifying T-cells in a lab, and then returning the cells to the patient to fight disease. ACT has proven effective in boosting immune response against some cancers, but has shown limited and short-term impact against most solid tumors. This may be due to a number of factors, including that the T cells don’t recognize their targets well, they’re not effective in their microenvironments, or they don’t accumulate and remain active for long.

To maximize and sustain the T-cells’ effectiveness against the target, researchers engineered them to secrete FRα-directed BiTE™ molecules. BiTE molecules are specially engineered with two sides — one side attaches to a T-cell and helps it recognize its target (in this case, FRα), and the other side helps pull in more T-cells to fight the targeted cells. 

The engineered T-cells performed as hoped — they not only identified and destroyed their targets, but their presence also activated nearby T-cells to join the fight. Moreover, researchers found that preparing the T-cells with a mix of two immune signaling substances, interleukin-2 and interleukin-15, resulted in an even better therapeutic effect. 

“We believe this new approach for adoptive T cell therapy has the potential to generate potent anti-tumor immune responses against ovarian cancer and can benefit patients who may not otherwise respond to immunotherapy,” says Dr. McGray. “We are excited to continue to develop this T cell therapy and are actively conducting studies that will support a future clinical trial to treat ovarian cancer patients at Roswell Park.”

Though scientists still have more to learn, these results are deeply encouraging, and are a significant step toward more effective immunotherapies for ovarian cancer.

“We are grateful for the support from the OCRA in funding our research and supporting our research team, which directly contributed to the development of this promising new treatment for ovarian cancer. We look forward to continuing to work with the OCRA as we strive to translate our laboratory findings into effective immunotherapies that can benefit ovarian cancer patients.”

View the full study, “BiTE secretion by adoptively transferred stem-like T cells improves FRα+ ovarian cancer control,” in the Journal for ImmunoTherapy of Cancer.

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