Year: 2007
Type: review
Abstract: In vertebrates, the TLRs are a family of specialized immune receptors that induce protective immune responses when they detect highly conserved pathogen-expressed molecules.Synthetic agonists for several TLRs, including TLR3, TLR4, TLR7, TLR8, and TLR9, have been or are being developed for the treatment of cancer.TLR9 detects the unmethylated CpG dinucleotides prevalent in bacterial and viral DNA but not in vertebrate genomes.As discussed in this Review, short synthetic oligodeoxynucleotides containing these immune stimulatory CpG motifs activate TLR9 in vitro and in vivo, inducing innate and adaptive immunity, and are currently being tested in multiple phase II and phase III human clinical trials as adjuvants to cancer vaccines and in combination with conventional chemotherapy and other therapies.Nonstandard abbreviations used: CpG ODN, oligodeoxynucleotide(s) containing one or more unmethylated CpG dinucleotides; HBsAg, HBV surface antigen; IFA, incomplete Freund's adjuvant; KLH, keyhole limpet hemocyanin; MART1, melanoma-associated antigen recognized by T cells 1; NHL, non-Hodgkin lymphoma; NSCLC, non-small cell lung carcinoma; ODN, oligodeoxynucleotide; pDC, plasmacytoid DC; PS, phosphorothioate; PS ODN, ODN that have a nuclease-resistant phosphorothioate backbone.Conflict of interest: A.M. Krieg is a founder and employee of and shareholder in Coley Pharmaceutical Group and has a financial interest in the development of TLR9 agonists
DOI: 10.1172/jci31414
Author: Arthur M. Krieg
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2117684163