Methods and compositions for reducing immunosuppression by tumor cells
AssigneesDana-Farber Cancer Institute, Inc., The General Hospital Corporation
InventorsKai W. Wucherpfennig, Glenn Dranoff, Penghui Zhou, Donald Shaffer, Nir Hacohen, Harvey I. Cantor, Diana Alvarez Arias
Life of this patent
Estimating the term…
Abstract
The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.
Claims20
An immunoresponsive cell having tumor specificity comprising a vector, the vector comprising a sequence encoding a shRNA,
- wherein the shRNA comprises contiguous nucleotides complementary to a nucleic acid sequence of SEQ ID NO:
- 612, selected from a group consisting of SEQ ID NOS:
- 58-72 and 645-652.
A method of treating cancer associated with a regulatory subunit of Cblb in a subject, the method comprising administering to the subject an autologous T cell modified to express a tumor specific T-cell receptor or chimeric antigen receptor (CAR) and an shRNA,
- wherein the shRNA comprises contiguous nucleotides complementary a nucleic acid sequence of SEQ ID NO:
- 612, selected from a group consisting of SEQ ID NOS:
- 58-72 and 645-652;
- and
- wherein the CAR comprises an antigen binding domain, a transmembrane domain, a stimulatory domain, and a co-stimulatory domain.
A method of treating cancer associated with a regulatory subunit of Cblb in a subject in need thereof by silencing genes that inhibit T cell function comprising
- administering to the subject an immunoresponsive cell comprising a vector, the vector encoding a tumor-specific T-cell receptor or a chimeric antigen receptor (CAR) and a shRNA sequence,
- wherein the shRNA sequences comprise a sequence at least 12 contiguous nucleotides complementary to the mRNA sequence encoded by a nucleic acid sequence of SEQ ID NO:
- 612, selected from a group consisting of SEQ ID NOS:
- 58-72 and 645-652.
Dependencies are inferred from the claim text.