Conjugatable STING and TLR7 Agonists for Targeted Immunotherapy
Targeting STING or TLR7 is of particular interest for immunotherapies. Indeed, these PRRs (pattern recognition receptors) are expressed by dendritic cells and other antigen-presenting cells, and they trigger the production of pro-inflammatory cytokines that potentiate immune responses in cancer- or pathogen-driven disease models.
Conjugatable PRR ligands are designed to develop immunomodulatory drugs such as antibody-drug conjugates (ADCs, also known as ISACs) and antigen-adjuvant conjugates (AACs). These synthetic PAMPs are engineered with reactive functional groups that enable covalent attachment to peptides or proteins via a chemical linker.
Conjugatable PRR Ligand Formats Available
To facilitate your research on ADCs and vaccination, InvivoGen has developed conjugatable ligands with three distinct reaction handles:
- Maleimide ligands (STG-982, TL7-887): designed for straightforward and rapid conjugation to thiol-containing proteins, suitable for proof-of-concept and early-stage studies.
- Azido ligands (STG-968, TL7-975): designed for click-chemistry conjugation using commonly used DBCO linkers, enabling the development of multiple bioconjugate architectures.
- DBCO ligands (STG-1151): designed for click-chemistry conjugation to azido-functionalized proteins, supporting defined and reproducible conjugation workflows.
Key Components of PRR Bioconjugates
PRR bioconjugates comprise a conjugatable ligand and a peptide/protein of interest (POI). Depending on the conjugation strategy, a linker is necessary to bridge the ligand and the POI.
- The conjugatable ligand is a synthetic PAMP that is recognized by a specific PRR and triggers (agonist) or blocks (antagonist) inflammatory responses. Each conjugatable ligand features a defined reaction handle (e.g., free amine, carboxylic acid, azido group, or DBCO group), allowing controlled reaction with the linker.
- The POI determines the function of the bioconjugate. Monoclonal antibodies allow localized PRR activation and antibody-mediated effector functions. Antigenic peptides/proteins enable the co-delivery of antigen and synthetic PAMP to antigen-presenting cells (APCs), thereby facilitating improved antigen processing and presentation for the induction of adaptive immune responses.
- The linker is a chemical moiety that covalently bridges the ligand and POI.
Successful bioconjugation often requires multiple steps: (1) designing the linker, (2) modification of the ligand to react with the linker, and (3) treatment of the POI to expose amino-acidic conjugation sites.
