Lasofoxifene Enhances Immunotherapy Efficacy by Promoting Antitumor Activity
核心洞察
A recent study reveals that lasofoxifene, an anti-estrogen therapy, enhances immunotherapy efficacy by promoting antitumor activity of eosinophils.
Lasofoxifene demonstrated superior efficacy compared to fulvestrant in reversing the detrimental effects of estrogens on tumor-associated eosinophilia in a TNBC mouse model.
Sermonix Pharmaceuticals (搜索) is currently investigating lasofoxifene in combination with abemaciclib in the ELAINE-3 trial for ESR1 (搜索)-mutated metastatic breast cancer (搜索).
Sermonix Pharmaceuticals (搜索) Inc. has announced findings from a Duke Cancer Institute study indicating that its investigational drug, lasofoxifene, can enhance the efficacy of immunotherapy by promoting the antitumor activity of eosinophils. The study, published in Science Advances, highlights lasofoxifene's potential as a combination agent across various cancer types.
Eosinophils and Tumor Microenvironment
Eosinophils, a type of white blood cell, have been identified as influential in combating tumor progression. Tumor-associated tissue eosinophilia (TATE) is linked to better outcomes in patients with several cancer types, including colon, esophageal, gastric, oral, melanoma (搜索), and liver cancers (搜索). The research indicates that estrogens can decrease TATE and reduce the effectiveness of immunotherapies.
Lasofoxifene's Impact on Immunotherapy
The study demonstrated that lasofoxifene was more effective than fulvestrant in reversing the detrimental effects of estrogens on tumor-associated eosinophilia and restoring potency to immunotherapies in a triple-negative breast cancer (搜索) (TNBC) mouse model. This is particularly significant as TNBC is an aggressive form of breast cancer (搜索) that lacks estrogen, progesterone, and HER2 receptor proteins.
"Lasofoxifene, which demonstrated superior efficacy than fulvestrant, also has been shown to be a well tolerated oral therapy in multiple clinical studies, making it a promising regulator of TATE/tumor growth," said senior author Donald McDonnell, Ph.D., professor at Duke University School of Medicine.
Clinical Development and Future Directions
Sermonix is currently investigating the combination of lasofoxifene and abemaciclib in the Phase 3 ELAINE-3 trial for ESR1 (搜索)-mutated metastatic breast cancer (搜索). The company has licensed patents from Duke covering the use of lasofoxifene in ESR1-mutated breast cancers and holds options on additional patents for enhancing TATE and immunotherapy efficacy in different cancers.
"Sermonix is excited by this new Duke Cancer Institute research, which suggests lasofoxifene's potential as a viable immunotherapy combination agent across a broad spectrum of cancer types," said Dr. David Portman, Sermonix chief executive officer. He added that the research further demonstrates the need to continue examining the drug's potential as an effective therapy in combination with other treatments to help patients confront cancer.