Golcadomide with CD20 T-cell engager extends survival in lymphoma model by boosting T-cell activation and trafficking

Immune-based therapies, such as CAR T and T cell bispecific antibodies, redirect T-cells to target antigens expressed on the malignant cells, have demonstrated promising antitumor and clinical activity. However, even with these advanced therapies some patients do not have non-durable responses, potentially due to tumor microenvironment factors such as lack of T-cell infiltration.

Golcadomide, a potential first-in-class Aiolos and Ikaros degrading CRBN E3 ligase modulator (CELMoD), has a multifaceted mechanism of action, including direct antitumor effects and T-cell activation. This study demonstrates that through specific degradation of transcription factors, Aiolos and Ikaros, golcadomide enhances T-cell function through increased proliferation and cytokine production. Spatial transcriptomic and multiplex immunofluorescence data revealed that single agent golcadomide treatment enhanced T-cell functions in a syngeneic GEMM lymphoma model, including T-cell activation and trafficking to the TME, suggesting potential synergy with T-cell engagers.