On August 24, 2020 Compass Therapeutics, Inc. a clinical-stage biotechnology company developing proprietary antibody therapeutics intended to engage the immune system to treat both solid tumors and hematological malignancies, reported the publication in the journal Science of preclinical data supporting CTX-2026, the Company’s novel anti-CD277 antibody product candidate (Press release, Compass Therapeutics, AUG 24, 2020, View Source [SID1234563985]). The paper describes the discovery and preclinical characterization of CTX-2026, a fully human antibody that binds to the CD277 antigen expressed on members of the butyrophilin family, including BTN3A1, and has been shown to engage two T cell subsets, gamma delta and alpha beta, to overcome the immunosuppressive tumor microenvironment associated with ovarian cancer.

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The paper entitled "BTN3A1 Governs Antitumor Responses by Coordinating Alpha Beta and Gamma Delta T-Cells," was co-authored by Jose R. Conejo-Garcia, M.D., Ph.D., and other researchers at Moffitt Cancer Center, researchers from The Wistar Institute, and Compass Therapeutics scientists.

"Ovarian cancer has been one of the most difficult cancers to treat, with a significant unmet need in the United States and around the world. I am encouraged by these data which not only suggest that BTN3A1 may play an important role in ovarian cancer but also demonstrate that CTX-2026 binding to BTN3A1 overcame the immunosuppressive microenvironment of ovarian cancer and delayed malignant progression in preclinical tumor models," said Thomas Schuetz, M.D., Ph.D., co-founder and chief executive officer at Compass Therapeutics. "We are excited about this program and its potential to deliver a novel, immune-oncology therapeutic candidate."

"This research demonstrates that targeting BTN3A1 orchestrates cooperative killing of established tumors by alpha beta and gamma delta T cells, and could enable novel interventions for malignancies resistant to existing immunotherapies," said Dr. Conejo-Garcia, Co-Leader of the Immunology Program and Chair of the Department of Immunology, Moffitt Cancer Center.

Highlights from the publication include:

BTN3A1 is overexpressed in malignant ovarian cancers, compared to benign ovarian tumors and normal tissues. Consistent with its immunosuppressive role, higher average BTN3A1 expression in samples from 200 ovarian cancer patients with clinical data was associated with significant reduction in patient survival.
CTX-2026, an anti-CD277 antibody, elicited coordinated alpha beta and gamma delta T cell responses, preventing alpha beta T cell inhibition while inducing gamma delta T cell activation to suppress the growth of established ovarian tumors in preclinical models.
CTX-2026 antibodies transform BTN3A1 from an immunosuppressive to an immunostimulatory mediator, restoring pre-existing anti-tumor immune responses in immunocompetent syngeneic mouse models.
Targeting CD277 by CTX-2026 was associated with greater activity than a PD-1 blocker in the orthotopic xenograft and syngeneic models of ovarian cancer.