Crystal structure of cobolimab, an investigational antibody against Tim-3 for cancer immunotherapy, in complex with anti-kappa nanobody

Crystal structure of cobolimab, an investigational antibody against Tim-3 for cancer immunotherapy, in complex with anti-kappa nanobody

Cobolimab is an investigational antibody targeting Tim-3, an immune checkpoint protein associated with the suppression of T-cell response against cancer cells. This antibody’s safety and anti-tumor effectiveness were made clear in the clinical trial of the combination therapy using cobolimab and a PD-1 antibody. Here, the crystal structure of the cobolimab Fab in complex with an anti-kappa nanobody is determined. The crystals belonged to the space group C2221, with unit cell parameters a = 64.30, b = 119.30, and c = 184.49 Å. The structure was refined to a resolution of 2.02 Å with Rwork/Rfree = 0.197/0.233. The nanobody in the structure facilitated crystallization by restricting the elbow flexiblity of the Fab and providing extra packing interface for crystallization. This structure can be used as a model structure for predicting the protein-protein interaction between cobolimab and Tim-3.