APC Activator

APC Activators (or Antigen-presenting cell activators) are a type of immunotherapy which leverages antigen-presenting cells (APCs) to drive an adaptive immune response.^[1][2][3][4] APC Activators are agonists to APC surface-expressed ligands that, when bound, induce the maturation and activation of APCs. Professional antigen-presenting cells – including dendritic cells, macrophages, and B cells – serve an indispensable role in the adaptive immune response through their unique ability to phagocytose, digest, and present exogenous (circulating) antigens to T cells, facilitating antigen-specific immune responses.^[5]

Professional APCs express MHC class II and CD40 molecules as surface receptors, and can be activated through direct interactions with T cells expressing these receptors' corresponding ligands, LAG-3 and CD40-L, respectively.^[5] A third class of receptors that can activate APCs are called toll-like receptors (TLRs); these receptors bind foreign ligands which are structurally conserved molecules from microbes, called pathogen-associated molecular patterns (PAMPs).^[6]

Combinatorial approaches that target multiple aspects of the cancer immunity cycle, including APC activation, are promising strategies for the treatment of diseases, including numerous types of cancer.^[7] Interest in the clinical use of TLR and CD40 agonistic antibodies in immuno-oncology wavered in the past decade.^[6][8] The APC Activator IMP321 (Eftilagimod alpha), a soluble LAG-3 fusion protein, is currently undergoing clinical trials in combination with chemotherapy (paclitaxel), or immune checkpoint inhibitors, including the PD-1 monoclonal antibody pembrolizumab, to accelerate the adaptive immune response in several tumor indications.^[9][2][4]