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Antibody Discovery Platform for CAR-T Cell Targeting and Drug Conjugation

Description:

Screening platform for identification of potent and specific nanobodies for (i) directing CAR-T cells to cancer cells, (ii) drug conjugation, or (iii) tumor imaging or diagnosis.

 

Inventor

Xianxin Hua, M.D., Ph.D.

 

Identification of antibodies capable of mediating CAR-T killing is challenging due to several reasons. First, the antibody has to have certain affinity to allow for sufficient binding time permitting the T cell to kill the target cells. Second, the scFv derived from the antibody must be conserve the affinity and specificity, followed by fusion with the rest of the CAR construct. Third, the antibody must bind to the appropriate location of the cell surface protein on the cancer cell to allow a certain distance between the T cell surface and the tumor cell surface to form effect immune synapse. There is a need for technologies allowing for efficient identification of potent, specific antibodies for CAR-T cell therapies.

 

Dr. Xiaxin Hua and his team have developed Sequential Tumor-related Antibody and antigen Retrieving (STAR) technology that allows to efficiently identify nanobodies fully capable of binding to tumor cell surface antigens and guide the CAR-T cells in vivo to the specific tumors. Nanobodies are tested for cross-reactivity with other tissues in vivo. The technology was successfully validated for generating nanobodies for targeting AML and neuroendocrine tumors, tested in switchable CAR system.

 

Applications

Identification of tumor-specific nanobodies that can be used for:

• CAR-T cell targeting

• Conjugation with anticancer drugs

• Tumor diagnosis, treatment monitoring, and imaging

 

Advantages

• Can be used for various tumor types/lines

• Nanobodies have small size, high affinity, low immunogenicity in humans

• Nanobodies are capable of recognizing uncommon or hidden epitopes

• Nanobodies able to bind into cavities or active sites of protein targets

 

Stage of Development

• Unique nanobodies successfully targeting AML and neuroendocrine tumors

 

Intellectual Property

Provisional Pending 

 

Desired Partnerships

1. License

2. Co-development

 

Docket #

18-8498


Patent Information:
For Information, Contact:
Linara Axanova
Associate Director, PSOM Licensing Group
University of Pennsylvania
axanova@upenn.edu
Inventors:
Xianxin Hua
Keywords: