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Selective phagocytosis of human cancer cells as target for immunotherapy

Description:

Cell therapy based methods to reduce tumor growth by disrupting the CD47-SIRPα interaction and targeting cells for phagocytosis with antibodies.

 

Inventor

Dennis Discher, Professor of Chemical and Biomolecular Engineering

 

Problem

Current cancer treatments (i.e. radiation, chemotherapy, etc.) result in multiple serious side effects due to lack of treatment specificity.  Cancer immunotherapies in development target the CD47-SIRPα interaction in order to incite local macrophages to engulf cancer cells, but tumor associated macrophages in solid tumors do not exhibit strong anti-tumor properties. In addition, CD47 is abundant on all healthy cells, so that targeting CD47 will generally harm healthy cells and lead to a variety of unwanted side effects such as anemia.  A therapy that enhances macrophage phagocytosis specifically of tumor cells and also avoids broad targeting of CD47 will reduce tumor size without the complications of current treatment regimens.

 

Solution

The Discher lab has developed a method to selectively enhance phagocytosis of cancer cells by macrophages.  More specifically, the researchers have demonstrated efficacious treatment of solid tumors by a mechanism of macrophage infiltration and stimulation combined with CD47-SIRPα disruption. A reduction in tumor size comparable to or better than chemotherapeutic treatments was observed in mouse models together with maintenance of normal parameters for blood and body weight.  This approach will allow for a treatment strategy in which cancer cells are selectively targeted for phagocytosis via macrophages while healthy cells are unaffected.

 

 

 

 

Advantages

•       Bone marrow derived macrophages and antibodies readily penetrate solid tumors from circulation

•       Injected cells and antibodies did not cause significant anemia, thrombocytopenia, or weight loss in mice

•       Phagocytosis of tumor cell subpopulations in both tumor periphery and core

•       Cost-effective treatment

  

 

Stage of Development

•       In vivo testing 

 

Intellectual Property

•       Provisional Pending

 

Reference Media

Alvey CM et al.  Blood, 2015, 126(23): 2214.

Spinler KR, et al.  Selective phagocytosis of human cancer cells in solid tumor xenografts after impeding CD47 “self” signals and injecting polyclonal anti-human IgG, manuscript in preparation. Poster presented at American Society of Hematology Annual Meeting, Orlando 2015.

Rodriguez PL, et al.  Science, 2013, 339(6122): 971-975.

Tsai RK, et al.  Blood Cells, Molecules, and Disease, 2010, 45: 67-74.

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Desired partnerships

• License

Co-development

 

 

Download PDF

 

Docket #  15-7496 


Patent Information:
For Information, Contact:
Joshua Jeanson
Associate Director, SEAS/SAS Licensing Group
University of Pennsylvania
jeanson@upenn.edu
Inventors:
Dennis Discher
Keywords:
Biotechnology