This invention introduces a dual payload antibody drug conjugate platform that delivers both a potent cytotoxic agent and a TLR7 agonist to tumors with controlled, site specific attachment. By uniting targeted cell killing with localized immune activation in a single biologic, the approach improves therapeutic index, overcomes resistance, and enhances anti tumor immune responses.
Cancer therapies often struggle to balance targeted tumor destruction with the activation of durable anti tumor immunity. Conventional treatments relying on a single mode of action face resistance, limited immune engagement, and systemic toxicity. Developing a stable, dual action biologic that can deliver both a cytotoxic and an immunostimulatory payload in a controlled, manufacturable format remains a major challenge for next generation oncology therapeutics.
This invention discloses a site selective dual payload antibody drug conjugate platform, exemplified by Sacituzumab conjugated with a cytotoxic payload (MMAF or MMAE) at an engineered Q295 site and a TLR7 agonist attached to endogenous cysteines. The approach achieves defined drug to antibody ratios (~2 cytotoxin and ~8 TLR7 agonist molecules) and delivers both direct tumor cytotoxicity and localized immune activation. The invention further includes engineered Fc region variants with tailored amino acid substitutions, glycoengineering, and isotype swaps to fine tune effector functions such as ADCC, ADCP, and CDC, optimizing immune modulation and safety across multiple disease contexts.
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• Dual mechanism of action combining cytotoxic tumor killing and immune activation
• Controlled, site specific conjugation producing reproducible drug antibody ratios
• Enhanced immunogenic cell death leading to stronger adaptive immune responses
• Customizable Fc engineering for precise tuning of effector functions and safety
• Reduced off target toxicity through tumor targeted antibody delivery
• Broad platform potential for oncology, autoimmune, and infectious disease therapies
• Improved manufacturability and scalability through defined conjugation chemistry
• Dual payload ADC therapy for solid tumors and resistant cancers
• Fc engineered antibodies for autoimmune disease modulation
• Antibody based immunotherapies enhancing TLR7 driven immune activation
• Targeted biologics for infectious disease treatment through immune stimulation
• United States Provisional Patent Application No. 63/502176 filed May 15 2023 converted May 11 2024 status Converted
• PCT Application No. PCT/US2024/029346 filed May 15 2024 published as WO 2024/238588 on January 10 2025 status Filed
Lab Validation
This technology is available for licensing.
Well suited for biopharmaceutical partners developing next generation ADCs, immune stimulating biologics, and targeted therapies requiring controlled, multi payload conjugation strategies.
Information available upon request.