AACR 2022 | Combining chemotherapy, CD40 agonist, and Flt3 ligand in triple-negative breast cancer

Sangeetha M. Reddy, MD, UT Southwestern Medical Center, Dallas, TX, explains the rationale behind combining chemotherapy, a CD40 agonist, and an Flt3 ligand in triple-negative breast cancer (TNBC). Breast cancer is associated with defects in antigen presentation, which may contribute to resistance to immune checkpoint blockade (ICB). The Flt3 ligand is a growth factor that increases the differentiation of DC1 dendritic cells, critical mediators of antigen presentation. The CD40 agonist activates all three classes of antigen-presenting cells. Synergy has been demonstrated between the Flt3L ligand and CD40 agonist and between the CD40 agonist and chemotherapy in other cancers. However, the combination of all three has not been studied in breast cancer. Dr Reddy explains that the combination was initially studied in mouse models to see if it was a viable strategy for clinical trials. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.