Toll-like receptor 3 (TLR3) and Melanoma differentiation-associated protein 5 (MDA5) (TLR3/MDA5)

Pattern recognition receptors (PRRs) engaged by the poly-ICLC adjuvant primarily include Toll-like receptor 3 (TLR3) and Melanoma differentiation-associated protein 5 (MDA5) [Sultan et al., 2020, Front. Immunol.]. Poly-ICLC is a synthetic double-stranded RNA (dsRNA) analog stabilized with poly-L-lysine and carboxymethylcellulose, designed to mimic viral genetic material and stimulate the innate immune system [Jasani et al., 2009, Vaccine]. TLR3, located in endosomes, recognizes dsRNA and signals through the TRIF adapter protein, while MDA5 acts as a cytoplasmic sensor signaling via the MAVS protein [Caskey et al., 2011, J. Exp. Med.]. This dual engagement triggers a robust production of Type I interferons and pro-inflammatory cytokines, facilitating the maturation of antigen-presenting cells and the activation of cytotoxic T lymphocytes [Martins et al., 2015, Vaccine]. In clinical applications, these receptors are targeted to enhance the immunogenicity of vaccines and to modulate the tumor microenvironment in cancer therapy [Butowski et al., 2009, J. Clin. Oncol.]. The activation of these PRRs is a key strategy in converting immunologically cold tumors into hot tumors, thereby improving the efficacy of other immunotherapies like checkpoint inhibitors.

Other names

Toll-like receptor 3Melanoma differentiation-associated protein 5IFIH1RIG-I-like receptorsRLRsdsRNA sensorsHiltonol targets

Agonist of Toll-like receptor 3 (TLR3) and Melanoma differentiation-associated protein 5 (MDA5), inducing Type I interferon and cytokine production via TRIF and MAVS pathways.