APVO442: A Promising Preclinical Candidate in the Fight Against Prostate Cancer

A Seattle-based biotech, is stepping up with APVO442, a promising preclinical bispecific antibody aimed at transforming prostate cancer treatment by unleashing the body’s immune system against tumors with greater precision and fewer side effects.

Built on proprietary ADAPTIR-FLEX platform, APVO442 is designed to target prostate-specific membrane antigen (PSMA), a protein highly expressed on prostate cancer cells, while simultaneously engaging CD3 on T cells to direct immune attacks specifically at tumors. This dual-targeting approach uses a low-affinity CD3 binding domain, known as CRIS-7, to minimize off-target effects and reduce the risk of cytokine release syndrome, a dangerous side effect seen in some immunotherapies. Unlike competing therapies that rely on acidic tumor environments or pre-activated immune cells, APVO442’s design prioritizes tumor-specific action, potentially offering a safer and more effective option for patients with advanced prostate cancer.Preclinical results have fueled optimism about APVO442’s potential.

Animal models studies revealed significant tumor reduction in PSMA-positive prostate tumors, driven by potent T-cell redirection and cytotoxicity. Importantly, the antibody showed minimal impact on healthy tissues, with reduced peripheral T-cell activation, suggesting a lower risk of systemic toxicity. The CRIS-7 domain, also used in another clinical-stage candidate (mipletamig) for acute myeloid leukemia (AML), has shown no cytokine release syndrome in preclinical settings, bolstering confidence in APVO442’s safety profile.

Early human trials of mipletamig for AML achieved an impressive 85% remission rate; hopefully, APVO442 will yield similarly positive results in treating prostate cancer.

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