Anti-epidermal growth factor receptor variant III chimeric antigen receptors and use of same for the treatment of cancer
Inventors
Morgan, Richard A. • Rosenberg, Steven A.
Assignees
US Department of Health and Human Services
Publication Number
US-10570214-B2
Publication Date
2020-02-25
Expiration Date
2032-03-21
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain of human antibody 139, an extracellular hinge domain, a transmembrane domain, and an intracellular domain T cell receptor signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are also disclosed.
Core Innovation
The invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain of human antibody 139, an extracellular hinge domain, a transmembrane domain, and an intracellular T cell receptor signaling domain. The CARs have antigen specificity for epidermal growth factor receptor variant III (EGFRvIII), a mutant form of EGFR expressed in various cancers such as glioblastoma. The invention also provides related nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions related to the CARs.
The CARs of the invention specifically target EGFRvIII, expressed in about 30% to 50% of glioblastoma multiforme (GBM) and other cancers, while substantially avoiding normal tissues as EGFRvIII is not present in non-cancerous cells. This provides antigen-specific immune responses against EGFRvIII-expressing tumor cells, potentially reducing or eliminating tumors by facilitating immune cell infiltration and enhancing anti-tumor responses.
The problem being solved is the poor prognosis of gliomas and other brain cancers despite advances in conventional treatments such as surgery, radiation, and chemotherapy. There is an unmet need for additional treatments for cancer, especially gliomas, where most patients with glioblastoma multiforme survive less than 15 months from diagnosis. This invention addresses this by creating CARs that redirect T-cell specificity for EGFRvIII-expressing tumor cells to improve cancer detection, prevention, and treatment.
Claims Coverage
The patent includes one independent claim focused on a method of treating cancer using a population of cells expressing a specific chimeric antigen receptor (CAR). There is one main inventive feature described in this claim.
Method of treating cancer using CAR-expressing cells specific for EGFRvIII
A method of treating cancer in a mammal, comprising administering a population of cells expressing a chimeric antigen receptor (CAR) that has antigen specificity for epidermal growth factor receptor variant III (EGFRvIII). The CAR comprises an amino acid sequence selected from SEQ ID NOS: 10 or 11, which include human antibody 139-derived antigen binding domains linked to T cell signaling domains.
The claims cover methods of cancer treatment using populations of host cells expressing CARs specifically targeting EGFRvIII with disclosed amino acid sequences, and further include features about pharmaceutical compositions, cancer types such as glioma, cancer specificity, host cell vector sequences, and population homogeneity.
Stated Advantages
The CARs target EGFRvIII, which is not expressed in normal tissues, thereby substantially avoiding off-target destruction of healthy cells.
The CARs enable non-MHC-restricted antigen recognition by T cells, allowing them to bypass common tumor escape mechanisms.
Inclusion of costimulatory domains such as CD28, 4-1BB, and CD3ζ in the CAR constructs enhances T cell activation, differentiation, survival, and anti-tumor activity.
Documented Applications
Treatment or prevention of cancer characterized by expression of EGFRvIII, including gliomas such as glioblastoma multiforme (GBM).
Methods of detecting presence of cancer in a host by contacting host cells with CARs or related antibodies and detecting complexes indicative of cancer.
Use of CARs, nucleic acids, vectors, host cells, antibodies, and pharmaceutical compositions in immunotherapy for cancers expressing EGFRvIII.
Interested in licensing this patent?