Natural toll-like receptor agonists in prophylactic vaccines for dendritic cell activation

Abstract

There is an unmet need for novel and effective treatments for lymphoma, the fifth most common malignancy in the US. In situ vaccination—an immunotherapeutic maneuver involving local irradiation, intratumoral (i.t.) injections of Flt3L and Toll-like receptor (TLR) agonist—has been shown in recent clinical trials ({type:clinical-trial,attrs:{text:NCT00185965,term_id:NCT00185965}}NCT00185965, {type:clinical-trial,attrs:{text:NCT00880581,term_id:NCT00880581}}NCT00880581, {type:clinical-trial,attrs:{text:NCT00226993,term_id:NCT00226993}}NCT00226993) to induce partial and complete remissions in patients with low-grade lymphoma[1]. The strength of anti-tumor response correlates with the potency of immunogenic dendritic cells (DCs) to efficiently uptake and present tumor antigens to T cells[2]. While the latest clinical trial {type:clinical-trial,attrs:{text:NCT01976585,term_id:NCT01976585}}NCT01976585 employs Poly-ICLC—a synthetic TLR3 agonist—to activate DCs, we hypothesize that “natural” TLR agonists (nTLRa) contained within prophylactic vaccines could simultaneously target multiple TLRs and be repurposed as clinical-grade DC activators for the in situ vaccination maneuver[3].