CAPTN-3

CAPTN-3 is a novel, conditionally activated tri-specific antibody platform developed by Purple Biotech. It is designed to engage both T cells and natural killer (NK) cells to mount a potent, localized anti-tumor immune response within the tumor microenvironment (TME). The platform features three functional arms: - An anti-CD3 arm that is conditionally activated by proteases present in the TME, ensuring selective engagement of T cells only at the tumor site. - An anti-NKG2A arm that blocks the NKG2A checkpoint on NK and CD8+ T cells, thereby unleashing their cytotoxic activity against tumor cells. - A third arm targeting a tumor-associated antigen (TAA), such as 5T4 (trophoblast glycoprotein/TPBG), which is overexpressed in various solid tumors. The lead compound from this platform, IM1240 (aCD3xa5T4xaNKG2A), has demonstrated significant preclinical efficacy including sustained regression of triple negative breast cancer xenografts and dose-dependent activity in non-small cell lung cancer patient-derived explants. The conditional activation mechanism minimizes off-target effects and cytokine release, potentially improving safety. CAPTN-3’s plug-and-play scaffold allows for flexible integration of different antibodies to address diverse cancer targets. The technology aims to overcome immune evasion mechanisms—particularly those mediated by the HLA-E/NKG2A axis—and reinvigorate exhausted immune effector populations within tumors[1][2][3][4][5][6][8].