Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity

Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors

“…This approach has advantages in targeting heterogeneous tumors. Paul Beavis and colleagues reported that adoptively transferred T cells expressing the DC growth factor Flt3L promoted the proliferation and differentiation of local dendritic cells and promoted endogenous antitumor T cell epitope spreading in solid cancers (108). This strategy may overcome tumor heterogeneity and should be given consideration to treat CNS tumors.…”

Revisiting T Cell Tolerance as a Checkpoint Target for Cancer Immunotherapy

“…It is often assumed that antigen release by CTL in these contexts will trigger "epitope spreading" by priming new anti-tumor responses within the draining lymph node, however, antigen release by CTL killing alone is insufficient to activate the innate immune system, and thus leads to tolerance in the draining lymph node (58). Consistent with this idea, a recent study leveraging CAR T cells to recruit more DCs to tumors was only capable of eliciting substantial epitope spreading within the draining lymph node when co-delivered with immune agonists that trigger DC immunogenicity and engage T cell co-stimulatory signaling (199). Thus, tumors can exploit a range of peripheral tolerance mechanisms to evade immunity.…”

CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?

“…[163][164][165] Likewise, one recent study has demonstrated that engineering T cells to secrete the FLT3 ligand promotes epitope spreading. 166 Restricting CAR Activity to Tumor Sites CAR activity can be restricted to tumor sites by several measures. First, CAR expression can be induced once T cells have migrated to tumor sites with small molecules, such as a doxycycline-inducible expression system.…”