Treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor
Inventors
Mason, Nicola • Powell, JR., Daniel J. • PANJWANI, Mohammed Kazim • SMITH, Jenessa • Cooper, Laurence J.N. • O'Connor, Colleen M.
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Assignees
University of Pennsylvania Penn • University of Texas System
University of Pennsylvania (Penn)The University of Pennsylvania (Penn), founded in 1740 by Benjamin Franklin, is a world-renowned Ivy League institution located in Philadelphia. Penn is dedicated to advancing knowledge, fostering innovation, and making a positive impact locally and globally. With a strong commitment to interdisciplinary research, academic excellence, and community engagement, Penn offers a diverse and inclusive environment for students, faculty, and staff. The university is recognized for its leadership in research, robust financial aid programs, and a tradition of civic involvement. Penn's strategic initiatives, such as Penn Forward, focus on reshaping education, research, and service to meet the challenges of a rapidly changing world. The university is also a leader in sustainability, aiming for carbon neutrality by 2042 and net-zero endowment emissions by 2050, and is home to a vibrant ecosystem of innovation, global engagement, and community partnership.
The University of Pennsylvania (Penn), founded in 1740 by Benjamin Franklin, is a world-renowned Ivy League institution located in Philadelphia. Penn is dedicated to advancing knowledge, fostering innovation, and making a positive impact locally and globally. With a strong commitment to interdisciplinary research, academic excellence, and community engagement, Penn offers a diverse and inclusive environment for students, faculty, and staff. The university is recognized for its leadership in research, robust financial aid programs, and a tradition of civic involvement. Penn's strategic initiatives, such as Penn Forward, focus on reshaping education, research, and service to meet the challenges of a rapidly changing world. The university is also a leader in sustainability, aiming for carbon neutrality by 2042 and net-zero endowment emissions by 2050, and is home to a vibrant ecosystem of innovation, global engagement, and community partnership.
Abstract
The present invention relates to compositions and methods for the treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor. One aspect includes a modified canine T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity in canine.
Core Innovation
The present invention relates to compositions and methods for the treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor. One aspect includes modified canine T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity in canine.
Cancer is the leading cause of death for domestic dogs and standard of care treatment for dogs with spontaneous B cell NHL provides a median survival time of about 1 year with the majority of dog-patients relapsing with drug resistant disease. There is a significant demand for improved therapies for dogs with this common cancer and CAR T cells offer the possibility of long-term remission/cure; this invention addresses that need by providing isolated nucleic acids, vectors, isolated CARs, modified cells, compositions, and methods related to a canine CD20-specific CAR.
Claims Coverage
Overview: One independent claim is present. It defines a method of treating a CD20+ cancer in a canine by administering a modified cell that expresses a chimeric antigen receptor with specified domains and a defined anti-CD20 scFv.
Method of treating a CD20+ cancer in a canine
Administering to the canine a modified cell that expresses a chimeric antigen receptor comprising a canine CD20 antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the canine CD20 antigen binding domain comprises an anti-CD20 single-chain variable fragment (scFv) comprising SEQ ID NO: 2.
The independent claim covers a therapeutic method in which a modified cell expressing a CAR containing a canine CD20-binding scFv (SEQ ID NO:2) together with defined transmembrane, costimulatory and CD3 zeta signaling elements is administered to treat CD20+ cancer in a canine.
Stated Advantages
Improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments ascribed to the modified canine T cells of this invention.
Offers the possibility of long-term remission/cure of canine B cell lymphoma compared to standard of care chemotherapy outcomes described in the background.
Documented Applications
Adoptive cell therapy using modified canine T cells that express a canine CD20-specific CAR for treatment of canine CD20 positive diseases or conditions.
Pharmaceutical compositions comprising modified cells expressing a canine CD20-specific CAR together with a pharmaceutically acceptable carrier.
Use of a modified cell that expresses a canine CD20-specific CAR in the manufacture of a medicament for the treatment of cancer in a subject.
A method for stimulating a T cell-mediated immune response in a canine by administering a modified cell that expresses a canine CD20-specific CAR.
A method of treating a canine with a disease or condition by administering a modified canine T cell that expresses a canine CD20-specific CAR, wherein the disease or condition is a cancer and/or an autoimmune disease.
Treatment of CD20+ cancers specifically enumerated in the patent, including lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and other listed tumor types.
Use in generating autologous modified cell products and administering them to canine subjects (example: treatment of a dog with relapsed B cell lymphoma) [procedural detail omitted for safety].
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