University of Pittsburgh researchers have developed a novel universal chimeric antigen receptor (CAR) T cell technology that uses antibody drug conjugates (ADCs) as targeting adaptors. This approach combines the cytotoxic effects of ADCs with the targeted cell-killing capabilities of CAR T cells, offering a dual mechanism of action to avoid resistance and increase the therapeutic window.
Universal ADC CAR T cells combine cytotoxic drug delivery with CAR T cell activity with two designs: A) enhancing existing ADCs with universal CAR T cells that bind to the ADC to activate CAR T cell effector functions B) enhancing existing universal CAR T cells by adding cytotoxic drug activity to CAR T cell anti-tumor functions.
Description
This technology has two general embodiments: A) for enhancing existing ADCs, universal CAR T cells that bind directly to ADCs, and B) for enhancing existing universal CAR T cells, adaptors which contain a drug payload. For both approaches the cytotoxic payload is delivered to tumor cells and synergistically paired with CAR T cell-induced tumor cell killing. Universal CARs allow for key advances over traditional CARs, including limiting toxicity by titrating CAR T cell activity with adaptor dose and multi-antigen with multiple adaptors to avoid resistance due to antigen loss.
Applications
• Cancer therapy
• Enhancing ADC efficacy and overcoming resistance
• Enhancing CAR T cell efficacy
Advantages
This technology offers several unique advantages over traditional ADC and traditional CAR T approaches. By combining the mechanisms of ADCs and CAR T cells, it provides a robust approach for cancer cell killing, addressing resistance mechanisms otherwise associated with either treatment alone. The use of ADCs as adaptors for universal CARs is a novel concept, alleviating concerns about cytotoxic drug effects on T cells. This approach enhances the versatility and effectiveness of both CAR T cell therapies and ADC approaches, making them applicable to a wider range of cancers.
Invention Readiness
The concept has been defined and validated through in vitro studies and preliminary in vivo human tumor xenograft mouse models. In vitro data includes potent and specific anti-tumor function as well as the ability to overcome ADC-resistance with 2 FDA-approved ADCs using both unmodified ADC and tagged ADC modalities.
IP Status
Patent pending
