Anti-PS Antibodies Enhances PD-L1 Immune Checkpoint Blockade in Triple-Negative Breast Cancer

Peregrine Pharmaceuticals has announced preliminary findings from preclinical research showing that antiphosphatidylserine (PS) antibodies “similar to bavituximab” improves anti-PD-L1 immune checkpoint blockade’s antitumor activity in a mouse model of triple-negative breast cancer (TNBC).

Duke University Medical Center researchers presented (Poster Session B36) the findings at the American Association for Cancer Research (AACR)’s Tumor Immunology and Immunotherapy Conference, held October 20-23, 2016, in Boston.

The research team found that PS enhanced anti-PD-L1 therapy’s antitumor activity in the E0771 mouse model of TNBC after chemotherapy, radiotherapy, or photodynamic therapy.

Chemotherapy, radiotherapy, and photodynamic therapy were all associated with subsequently increased PS expression on tumor cells, the researchers noted.

“PS expression is upregulated by chemotherapy, radiotherapy, and photodynamic therapy in vitro,” reported lead study author Kensuke Kaneko, PhD, of Duke University in Durham, NC, and coauthors in the poster session. “A combination therapy blocking PS by PS-targeting mAb and immune checkpoint blockade with anti-PD-L1 mAb appears superior to single-agent therapy.”

Combining anti-PS and anti-PD-L1 therapy, with or without paclitaxel chemotherapy, “led to greater antitumor responses than any of the treatments administered as single agents or duel treatment combinations with paclitaxel,” the company announced.

The study is the latest in a series of such small, proof-of-concept preliminary studies. The company’s preclinical research employs ch1N11, “the preclinical equivalent of bavituximab,” in its animal studies.

Bavituximab (and mch1N11 [a novel mouse chimeric monoclonal antibody that targets PS]), investigational monoclonal antibodies, targets PS and PS-mediated inhibition of immune cell recognition of tumor cells; it is believed to weaken tumor-environment immunosuppression and thereby enhance tumor infiltration by lymphocytes. It also appears to decrease expression of tumor-promoting cytokines, which are elevated following anti-PD-1 monotherapy.

“Our future plan is to investigate the effect of local irradiation or photodynamic therapy combined with PS-targeting mAb and anti-PD-L1 Ab,” the coauthors reported.

Preliminary preclinical work has also shown that PS is associated with enhanced PD-1 and CTLA-4 blockade antitumor activity in mouse models of melanoma.

The National Comprehensive Cancer Network (NCCN) has recently announced grants for clinical study of bavituximab combination immunotherapy regimens against glioblastoma, head and neck cancer, and liver carcinoma, Peregrine announced.