ALDH1A2 Inhibition Enhances Antitumor DC Vaccine Efficacy

Strategies to stimulate dendritic cell (DC) activity, such as ex vivo generation and priming of DC vaccines, have been explored as cancer immunotherapies owing to their potential to elicit antitumor T cell responses. However, the success of DC vaccines has been limited, potentially because of unidentified tolerance-enforcing mechanisms.

In a recent publication in Nature Immunology, WuXi AppTec scientists contributed to a study showing that GM-CSF–IL-4-induced differentiating DCs express ALDH1A2 and produce retinoic acid, inhibiting DC maturation. In this work, the authors describe the development of an ALDH1A2 inhibitor with high potency, favorable drug-like properties and no evidence of off-target effects. Treatment with this inhibitor promoted DC activity, which in turn enhanced antigen-specific T cell responses, improving the efficacy of DC vaccines.