Your Donations in Action: Kathleen Capaccione, MD, PhD

Despite the dramatic improvements experienced by some cancer patients following immunotherapy, new treatments are needed to make therapeutic treatment more effective and longer lasting.

Prior research has demonstrated that combining targeted radiotherapy with immunotherapy could create a lasting response in some cancers, like melanoma. However, it has not been investigated in non-small cell lung cancer (NSCLC). In addition, recent research has shown that fibroblast activation protein (FAP)-targeted molecular radiotherapy can be effective against several cancers, yet it also has not been investigated in NSCLC.

For her 2019 RSNA Research Resident Grant project, “Image-guided Molecular Targeted Irradiation Against Malignant Melanoma,” Kathleen Capaccione, MD, PhD, assistant professor of radiology at Columbia University’s Vagelos College of Physicians and Surgeons and director of research mentorship in the Department of Radiology, and colleagues investigated the effects of FAP-targeted radiotherapy alone and in conjunction with checkpoint inhibitor immunotherapy in NSCLC and melanoma.

Listen as Dr. Capaccione discusses her research:

The team targeted FAP with the radiotherapy ¹⁷⁷Lu-FAPI-04 alone and then with immunotherapy in mouse models of melanoma and lung cancer. They found that ¹⁷⁷Lu-FAPI-04 alone significantly reduced tumor growth in both lung cancer and melanoma models. When combined with immunotherapy, in the case of melanoma, the treatment resulted in tumor regression. In lung cancer, the combined therapy slowed tumor growth, but tumors did not regress completely.

The study also investigated the mechanisms underlying these effects. Combined therapy led to decreased cell cycling and increased apoptosis. Flow cytometry showed distinct responses in tumor-associated macrophages with combined therapy.

“The combined effects of FAP-targeted radiotherapy and checkpoint inhibitor therapy are highly tumor-and context-dependent but have the potential to provide increased anticancer efficacy compared with either treatment alone,” Dr. Capaccione said.

The R&E Foundation grant opened the door to a significant three-year funding opportunity for Dr. Capaccione, who was recently named a Louis V. Gerstner, Jr. Scholar at Columbia.

“The RSNA grant gave me the boost to launch this work and obtain additional funding,” Dr. Capaccione said. “I will be able to conduct more in-depth research in preclinical models and through a translational study as we assess changes in FAP expression resulting from immunotherapy.”

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Read our previous Your Donations in Action article.