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Enhancing the Efficacy of Tumor Immunotherapy by Targeting Endothelin Receptor B

Description:

 

Antagonism of Endothelin Receptor B (ETRB) increases intratumoral T cell homing to tumors and enables tumor response to otherwise ineffective immunotherapy

 

Technology

 

Problem:

 

In spite of generating a tangible antitumor cellular immune response in peripheral blood, tumor vaccines have proven largely ineffective for treatment of solid tumors. The

success of immune therapy partly depends on the ability of effector cells to infiltrate tumors which in turn is dependent on tumor microenvironment. T cell trafficking through lymphoid organs and peripheral tissues is tightly controlled through endothelial addressing signals regulating homing, adhesion and transendothelial migration. Endothelium provides a barrier that prevents T cell infiltration and thus there is a need for new pharmacologic intervention to improve cancer immunotherapy without increasing systemic inflammation.

 

Solution:

 

Dr. Coukos and his team at Penn have developed methods of treating and enhancing efficacy of immunotherapy for a solid tumor by modulating the expression or activity of effector proteins such as ETRB, ET-1, ICAM-1 to guide T-cells to the tumor cells. They have shown that ETBR signaling blocks T cell adhesion to endothelium and ETBR blockade restored adhesion of T cells in vitro and markedly increased T cell homing to tumors. In addition, the endothelial molecular signature which includes ETBR, could assist in the selection of patients for whom ETBR blockade may enhance immunotherapy.

 

 

Applications:

 

Adjuvant therapy to tumor vaccines

 

Advantages:

 

Increase in anti-tumor immune response

 

Stage of Development:

 

In vivo data

 

Intellectual Property:

 

Issued US patents

9,289,426

10,174,120

 

Reference Media:

 

Kandalaft et al., Clin Cancer Res. 2009 Jul 15;15(14):4521.

 

Buckanovich et al, Nat Med. 2008 Jan;14(1):28.

 

Desired Partnerships:

 

License

 

Docket #: S4136

 

 


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