TLR Ligands Rationally Design

Creative Biolabs is a world-leader in the field of vaccine development who has focused on the cancer vaccines for years. The extensive experience and expertise of our scientists enable Creative Biolabs to provide innate immune stimulators related development services, including TLR ligands rationally design.

Toll-like Receptors (TLRs)

Toll-like receptors (TLRs) in particular are widely regarded as key players regulating innate and adaptive immune responses to antigens. Direct-targeting to TLRs using rationally designed subunit vaccine candidate with built-in TLR agonist has become a hot field of vaccine research and development.

TLR ligands and TLR signaling pathways.

Fig.1 TLR ligands and TLR signaling pathways. (Bing Du. 2016)

TLR Ligands

TLR1-TLR2 ligands. Unlike most TLRs that function alone, TLR2 functions by dimerizing with TLR1 or TLR6. Whereas the TLR1-TLR2 heterodimer is responsible for sensing triacylated lipopeptides of mycoplasma or Gram-negative bacteria origin, TLR2-TLR6 heterodimers sense diacylated lipopeptides of mycoplasma and Gram-positive bacteria origin. TLR2 ligands have been reported to function both as potent cancer vaccine adjuvants and as immunotherapeutic agents in several different mouse cancer models.

  • Bacterial Lipoprotein (BLP). Bacterial lipoproteins are excellent carriers for hapten-conjugates and builtin adjuvant in novel subunit vaccines development.

TLR3 ligands. TLR3 is an endosomal TLR which senses RNA viral infection in cells by recognizing intracellular dsRNA.

  • Poly I:C. Polyinosine-polycytidine (poly-IC), when properly combined with an antigen, can be used as a PAMP-adjuvant to activate a variety of elements of host defense in a pattern similar to viral infection.

TLR4 ligands. TLR4 recognizes highly toxic LPS structures of Gram-negative bacteria that are known to cause septic shock.

  • Monophosphoryl Lipid A (MPLA). Monophosphoryl lipid A is a well-characterized TRIF-biased agonist of TLR4 and has been utilized as adjuvants in some vaccines approved by U.S. FDA.
  • Glucopyranosyl Lipid Adjuvant (GLA). GLA is a highly potent adjuvant and can greatly enhance humoral and cellular immune responses.
  • Fibronectin Extra Domain A and B. The alternatively spliced extra domain A (EDA) and B (EDB) of fibronectin are highly expressed in tumor and essentially undetectable under normal conditions. Although not fully understood, FNIII EDA and EDB are known to stimulate Toll-like receptor 4 (TLR4).

TLR7 ligands. TLR7 recognizes viral single-strand RNA and imidazoquinoline derivatives.

  • Imiquimod (INN). Imiquimod can be used as an effective adjuvant for formulating DC-based anti-tumor vaccines.

TLR9 ligands. TLR9 is another endosomal TLR that recognizes intracellular DNA molecules of microbial origin because of the presence of unmethylated CpG motifs that are found in bacterial and viral genomes.

  • CpG ODN. CpG-ODN signal through TLR-9 on plasmacytoid dendritic cells to induce potent IFN-α production and, indirectly through natural killer cells, IFN-γ secretion.

Creative Biolabs is specialized in assisting clients with every stage of the vaccine industry, including TLR agonists development. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.


  1. Bing Du, et al. Targeting Toll-like receptors against cancer. J Cancer Metastasis Treat. 2016, 2: 463-70.

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