Potent immune agonists such as TLR7/8 activators can trigger strong anti-tumor and anti-infective responses, but systemic delivery often causes widespread immune activation and unacceptable toxicity. Current strategies lack sufficient selectivity and control, resulting in narrow therapeutic windows and limited clinical utility. Achieving stable circulation, targeted delivery, and controlled intracellular release of these agents remains a significant challenge. There is a need for approaches that can localize immune activation to disease sites while preserving systemic safety and improving treatment outcomes for cancer and infectious diseases.
The invention comprises antibody-drug conjugates in which a TLR7/8 agonist, typically based on an imidazoquinoline scaffold, is covalently linked to an antibody through a cleavable or non-cleavable linker. The antibody targets antigens on tumor or pathogen-infected cells, enabling selective binding and internalization. Upon intracellular processing, the linker releases the agonist locally, activating immune signaling pathways such as NF-κB at the disease site while reducing systemic exposure. This design allows precise control of immune activation, improves therapeutic index, and supports flexible adaptation across different antibodies, linkers, and disease targets.
• Reduces systemic immune toxicity through localized activation
• Enhances therapeutic efficacy via targeted intracellular release
• Improves therapeutic index compared to systemic TLR agonists
• Enables precise control of drug-to-antibody ratio
• Supports flexible design across multiple antibodies and linkers
• International (PCT): Application No. PCT/US22/70889; Publication No. WO 2022/187809; Filed 03/01/2022; Status: Filed
• United States: Application No. 18/547,594; Publication No. US 2024-0189440 A1; Filed 08/23/2023; Status: Filed
• Europe (EPO): Application No. EP22764251.9; Publication No. EP 4301417; Filed 03/01/2022; Status: Filed
• Canada: Application No. 3,211,468; Filed 03/01/2022; Status: Filed
• Mexico: Application No. MX/a/2023/009589; Filed 03/01/2022; Status: Filed
• Brazil: Application No. BR 11 2023 017916 5; Filed 03/01/2022; Status: Filed
• China: Application No. 202280031980.4; Publication No. CN117355341A; Filed 03/01/2022; Status: Filed
• Japan: Application No. 2023-553489; Filed 03/01/2022; Status: Filed
• South Korea: Application No. 2023-7033616; Filed 03/01/2022; Status: Filed
• Singapore: Application No. 11202306195W; Filed 03/01/2022; Status: Filed
• Hong Kong: Application No. 62024093589.5; Filed 03/01/2022; Status: Filed
• Australia: Application No. 2022228485; Filed 03/01/2022; Status: Filed
• New Zealand: Application No. 802639; Filed 03/01/2022; Status: Filed
• South Africa: Application No. 2023/07917; Filed 03/01/2022; Status: Filed
• Israel: Application No. 305355; Filed 03/01/2022; Status: Filed
In vivo and in vitro data
This technology is available for licensing.
Strong potential for pharmaceutical and biotechnology partners developing targeted immunotherapies for oncology and infectious disease indications.
Additional experimental data and technical details are available upon request.