Combination therapy to increase the efficacy of antibody-drug conjugates in bladder cancer

Unmet Need: Treatment to improve tumor response to antibody-drug conjugate therapies

Antibody-drug conjugates (ADCs) deliver drug payloads, such as chemotherapeutics, to a subset of cells based on the antibody’s recognition of its specific cell surface antigen, enabling higher doses delivered to the patient with fewer side effects. The FDA has recently approved two ADC therapies for the treatment of metastatic bladder cancer. However, the efficacy of these ADCs to kill cancer cells is limited when a tumor expresses low levels of the corresponding surface tumor antigen, which can occur as cancer cells adapt to evade treatment. Thus, new therapeutic avenues are needed to improve the efficacy of ADC therapies and expand treatment opportunities for patients with otherwise ADC-resistant tumors.

The Technology: Small molecule to improve tumor targeting by antibody-drug conjugates

This technology is a small molecule therapeutic that reprograms cancer cells to increase their sensitivity to existing antibody-drug conjugate (ADC) therapies for metastatic bladder cancer. This small molecule increases the expression levels of specific tumor antigens on the surface of cancer cells, facilitating broad recognition of cancer cells by the drug-carrying antibodies. As such, a greater proportion of bladder cancers, even those with low levels of tumor antigen, can be altered to express the tumor antigen, thereby increasing delivery of the chemotherapeutic drug to maximize cancer-killing potential.

This technology has been validated in human patient-derived bladder cancer organoids. Combination therapy with this small molecule increased the sensitivity of bladder cancer organoids to the FDA-approved ADC, Enfortumab vedotin, compared to treatment with this ADC alone.

Applications:

Combination therapy to improve efficacy of antibody-drug conjugate (ADC) therapies for bladder cancer
Combination therapy for metastatic triple-negative breast cancer
Combination therapy for ADC-resistant and metastatic bladder cancer
Personalized medicine for cancers with low tumor antigen expression
Research tool for cancer cell epigenetic reprogramming
Research tool for improved cancer cell targeting using ADCs and other biologics
Research tool to aid development of next-generation ADC therapies

Advantages:

Improves response of bladder cancer to FDA-approved antibody-drug conjugate (ADC) therapies
Expands therapeutic opportunities for tumors that are ADC-resistant or lack tumor antigen expression
Allows administration of higher chemotherapeutic doses with fewer side effects
Compatible with several existing ADC therapies

Lead Inventor:

Michael Shen, Ph.D.

Patent Information:

Patent Pending

Related Publications:

Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K, Chua CW, Barlow LJ, Kandoth C, Williams AB, Bergren SK, Pietzak EJ, Anderson CB, Benson MC, Coleman JA, Taylor BS, Abate-Shen C, McKiernan JM, Al-Ahmadie H, Solit DB, Shen MM. “Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer” Cell. 2018 Apr 5; 173(2): 515-528.

Tech Ventures Reference:

IR CU24095
Licensing Contact: Joan Martinez