Murine anti-NY-ESO-1 T cell receptors
Inventors
Parkhurst, Maria R. • Morgan, Richard A. • Rosenberg, Steven A. • Rosati, Shannon Faith
Assignees
US Department of Health and Human Services
Publication Number
US-10087230-B2
Publication Date
2018-10-02
Expiration Date
2033-05-22
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Abstract
The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for NY-ESO-1. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a mammal and a method of treating or preventing cancer in a mammal using the inventive TCRs or related materials.
Core Innovation
The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for NY-ESO-1 and comprising a murine variable region. The invention also encompasses related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, antibodies or antigen binding portions thereof, and pharmaceutical compositions. Furthermore, the invention includes methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal by using the inventive TCRs or related materials.
The problem being solved relates to obstacles in adoptive cell therapy for cancer treatment. Specifically, only about 50% of melanoma tumor samples generate tumor-reactive T cells, and generating tumor-reactive T cells from non-melanoma cancers is difficult. Additionally, many patients have tumors that are not amenable to surgical resection. Accordingly, there is a need for T cell receptors suitable for treating patients with cancer.
The inventive TCRs have antigenic specificity for NY-ESO-1, a cancer testis antigen expressed only in tumor cells and non-MHC expressing germ cells of the testis and placenta, and are capable of recognizing NY-ESO-1 in an MHC class I-dependent manner, preferably in the context of an HLA-A2 molecule. The TCRs comprise murine variable regions and preferably murine constant regions, providing improved expression, functionality, and specific targeting of multiple types of NY-ESO-1 expressing cancers while minimizing destruction of normal cells.
Claims Coverage
The patent includes one independent claim which covers a method involving administration of host cells expressing a TCR with specific features to a mammal for treating and binding to cancer cells.
TCR antigenic specificity and murine variable region
The method employs a TCR having antigenic specificity for NY-ESO-1 (SEQ ID NO: 1) and comprising a murine variable region.
TCR comprising specific amino acid sequences
The TCR comprises the amino acid sequences of SEQ ID NOs: 3-8.
Host cell expressing the TCR administered to mammal
The method comprises administering an isolated host cell or population thereof expressing the TCR to the mammal in an amount effective to specifically bind the TCR to NY-ESO-1 positive cancer cells.
Cancer cell types treated
The method applies to cancer cells including melanoma, breast cancer, lung cancer, prostate cancer, thyroid cancer, ovarian cancer, and synovial cell sarcoma cells.
TCR sequence variations
The TCR may also comprise amino acid sequences of SEQ ID NOs: 9 and 10, or SEQ ID NOs: 11 and 12, covering variable region sequences or full chain sequences.
The claims cover methods of treating mammals by administering host cells expressing murine variable region TCRs specific for NY-ESO-1 with defined amino acid sequences, targeting various types of NY-ESO-1 positive cancer cells, thereby providing therapeutic specificity and applicability.
Stated Advantages
Ability to target cells of multiple types of cancer expressing NY-ESO-1.
Minimized or eliminated destruction of normal non-cancerous cells, reducing toxicity.
Increased expression and/or functionality of murine TCRs on human host cells compared to human TCRs, leading to improved immune responses.
Documented Applications
Methods of treating or preventing cancer in a mammal using TCRs, polypeptides, proteins, nucleic acids, recombinant vectors, or host cells expressing TCRs specific for NY-ESO-1.
Methods of detecting the presence of cancer in a mammal by contacting cancer cell samples with inventive TCRs or related materials and detecting complexes formed.
Adoptive cell therapy, including transduction of human T cells with murine anti-NY-ESO-1 TCRs for targeting NY-ESO-1 expressing tumor cells.
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