TL7-887 (maleimide) and TL7-975 (azido) - Conjugatable TLR7 Ligands

TLR7 agonists for bioconjugation  - VacciGrade™

InvivoGen provides two conjugatable PRR ligands that target the Toll-Like Receptor TLR7 to foster research on immunotherapeutic tools. These ligands have been synthesized from the well-known specific TLR7 agonist CL307 and designed to allow the generation of bioconjugates after attachment to a protein of interest (POI) with a chemical linker.

— TL7-887 is a ready-to-use reagent, bypassing the need for linker design. It features a maleimide group that reacts with free thiols on the POI.

— TL7-975 allows a flexible choice of linker for conjugation to the POI. It features an azido group that reacts with an azido-reactive group on the linker.

Synthetic TLR7 agonists, like natural microbial TLR7 ligands, mediate NF-κB/AP1- and IRF-mediated production of type I IFNs (IFN-α/β) and pro-inflammatory cytokines in TLR7-expressing cells (i.e. dendritic cells, B cells, and other myeloid cells) [1]. Thus, they have been extensively studied as immuno-modulatory agents in tumor and infectious disease models [2]. In order to enhance TL7-887 and TL7-975 cellular uptake and delivery to TLR7 in the endosome, both ligands were engineered from the base molecule CL307, which consists of the adenine analog CL264 coupled with spermine. This biocompatible cationic polyamine also anchors a spacer with the maleimide or an azido group.

More details

Applications:

Conjugation to monoclonal antibodies to generate immunostimulatory antibody-drug conjugates (ADCs, also known as ISACs), or to antigenic peptide/proteins to generate antigen-adjuvant conjugates (AACs).

• ADCs (or ISACs) allow localized TLR activation and antibody-mediated effector functions [3,4].
• AAC vaccines allow the codelivery of antigen and TLR agonists to antigen-presenting cells (APCs) and thus, better antigen processing and presentation for the induction of adaptative immune responses [5].

Key features:

• Two formats: "pre-linked" for immediate use, or "click-chemistry compatible" for flexible choice of linker
• Biological activity has been confirmed using cellular assays
• Conjugation to a mAb (Anti-HER2-hIgG1 or Anti-TROP2-hIgG1) and subsequent activation of TLR7 has been validated using cellular assays
• Highly pure
• The absence of any bacterial contamination has been confirmed

TL7-887 and TL7-975 are VacciGrade™, a high-quality pre-clinical grade.

Learn more about bioconjugation

References

1. Georg P. & Sander L.E., 2019. Innate sensors that regulate vaccine responses. Curr. Op. Immunol. 59:31.
2. Bahgchandani S. et al., 2021. Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: from antiviral formulations to vaccine adjuvants. Adv. Drug Delivery Reviews. 175:113803.
3. Gadd A.J, et al. 2015. Targeted activation of toll-like receptors: conjugation of a toll-like receptor 7 agonist to a monoclonal antibody maintains antigen binding and specificity. Bioconjug. Chem. 26(8):1743.
4. Ackerman S.E, et al. 2021. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nat Cancer. 2(1):18.
5. Xu Z. & Moyle P.M, 2018. Bioconjugation approaches to producing subunit vaccines composed of protein or peptide antigens and covalently attached Toll-Like receptor ligands. Bioconjug. Chem. 29(3):572.