Poly(I:C) as cancer vaccine adjuvant: Knocking on the door of medical breakthroughs

Abstract

Although cancer vaccination has yielded promising results in patients, the objective response rates are low. The right choice of adjuvant might improve the efficacy. Here, we review the biological rationale, as well as the preclinical and clinical results of polyinosinic:polycytidylic acid and its derivative poly-ICLC as cancer vaccine adjuvants. These synthetic immunological danger signals enhanced vaccine-induced anti-tumor immune responses and contributed to tumor elimination in animal tumor models and patients. Supported by these results, poly-ICLC-containing cancer vaccines are currently extensively studied in the ongoing trials, making it highly plausible that poly-ICLC will be part of the future approved cancer immunotherapies.

Toll-like receptor 3-induced immune response by poly(D,L-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy

“…Poly I:C is a promising immunostimulant for cancer vaccines directed against intracellular pathogens and strongly drives cellmediated immunity and type I IFN response. 18,35 In addition, we demonstrated the therapeutic efficacy of DC-based immunotherapy using PLGA (OVA + poly I:C)-NPs in different tumor models and confirmed that antigen-specific CD8 + T cell activation contributed to inhibition of tumor growth.…”

Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts

“…22 Being an agent related to TLR3 agonist-based immunotherapy, polyinosinic-polycytidylic acid [poly(I:C)] has been used as a cancer vaccine adjuvant in several types of cancers, such as prostate cancer, lymphoma, lung cancer, melanoma, and hepatocellular carcinoma. 23,24 In human renal cell carcinoma cells, poly(I:C) treatment can downregulate c-Myc expression and facilitate reactive oxygen species (ROS) generation to induce DNA damage, cell growth arrest, and apoptosis via innate adjuvant receptors and the 2-5A system. 25 In NB, we have found that poly(I:C) may induce tumor cells apoptosis, preferentially through the mitochondrial pathway.…”

Computational drug ZINPIP-Analog an ultimate solution to cure conserved domains of mutant EGFR, ALK and BRAF Proteins in NSCLC

“…The alteration of the molecular structure of drug frequently prompts drugs with higher molecular weight, more rings, more rotatable bonds, and a higher lipophilicity that might affect the quality of drugs (Ammi et al, 2015) but our Ligand compound Zinpip analog fulfills all the properties of Lipinski rule of five that are shown in table 1.…”