The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, an
The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.
대표청구항▼
1. A method of treating cancer in a subject by administering a therapeutically effective amount of an isolated modified primary human T cell to a subject in need thereof, said therapeutically effective amount being one sufficient to kill cancer cells in the treated subject, wherein said isolated mod
1. A method of treating cancer in a subject by administering a therapeutically effective amount of an isolated modified primary human T cell to a subject in need thereof, said therapeutically effective amount being one sufficient to kill cancer cells in the treated subject, wherein said isolated modified primary human T cell is derived from a primary human T cell isolated from a human donor, and (i) is modified to functionally impair or to reduce expression of the endogenous T cell receptor (TCR), and (ii) is further modified to express at least one functional exogenous non-TCR that comprises a chimeric receptor which recognizes a ligand expressed on the surface of cancer cells in the treated subject, said chimeric receptor comprising a ligand binding domain attached to a signaling domain, wherein the isolated primary human T cell modified as in (i) and (ii) elicits no or a reduced graft-versus-host disease (GVHD) response in a histoincompatible human recipient as compared to the GVHD response elicited by a primary human T cell isolated from the same human donor that is only modified as in (ii), and further wherein the isolated modified primary human T cell recognizes and kills cancer cells. 2. The method of claim 1, wherein the chimeric receptor comprises a chimeric natural killer (NK) cell receptor. 3. The method of claim 1, wherein the chimeric receptor comprises a NKG2D, NKG2A, NKG2C, NKG2F, LLT1, AICL, CD26, or NKRP1 polypeptide. 4. The method of claim 1, wherein the ligand binding domain is obtained from an anti-tumor chimeric antigen receptor or an anti-tumor antibody. 5. The method of claim 1, wherein the chimeric receptor comprises a receptor that hinds to MIC-A, MIC-B, estrogen, progesterone, RON, or one or more members of the ULBP/RAET1 family. 6. The method of claim 5, wherein the one or more members of the ULBP/RAET1 family is/are selected from ULBP2, ULBP3, Rae-1, H-60, HCMV UL18, or Rae-1β. 7. The method of claim 1, wherein the ligand binding domain is a NKG2D ligand binding domain and the signaling domain is a CD3 signaling domain. 8. The method of claim 1, wherein the isolated modified primary human T cell is derived from an allogeneic T cell or primary human PBMCs isolated from a human subject. 9. The method of claim 1, wherein the isolated modified primary human T cell expresses CD4 or CD8. 10. The method of claim 1, wherein the isolated modified primary human T cell is capable of differentiating into a T regulatory cell. 11. The method of claim 1, wherein the isolated modified primary human T cell is capable of producing effector molecules. 12. The method of claim 11, wherein the effector molecules are interferon gamma (IFN-γ) and interleukin 2 (IL-2). 13. The method of claim 1, wherein the reduced GVHD response is evidenced by the isolated primary human T cell modified as in (i) and (ii) eliciting reduced expression of gamma interferon as compared to a primary human T cell isolated from the same human donor that is only modified as in GO. 14. The method of claim 1, wherein the reduced GVHD response is evidenced by the isolated primary human T cell modified as in (i) and (ii) not eliciting an increase in expression of gamma interferon as compared to a primary human T cell isolated from the same human donor that is only modified as in (ii). 15. The method of claim 1, wherein the isolated primary human T cell modified as in (i) and (ii) does not elicit a GVHD response in a human recipient.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (44)
Rosenberg, Steven A.; Chinnasamy, Dhanalakshmi, Anti-vascular endothelial growth factor receptor-2 chimeric antigen receptors and use of same for the treatment of cancer.
Daniel J. Capon ; Arthur Weiss ; Brian A. Irving ; Margo R. Roberts ; Krisztina Zsebo, Chimeric chains for receptor-associated signal transduction pathways.
Collingwood, Trevor; Cooper, Laurence J. N.; Gregory, Philip D.; Holmes, Michael C.; Miller, Jeffrey C.; Rebar, Edward J.; Reik, Andreas; Urnov, Fyodor, Methods and compositions for modification of a HLA locus.
Bender Jeffrey R. (Orange CT) Pardi Ruggero (Milan CA ITX) Engleman Edgar G. (Atherton CA), Natural killer cell lines and clones with antigen specificity.
Steinman Lawrence (Palo Alto CA) Oksenberg Jorge (Palo Alto CA) Bernard Claude (North Baldwin AUX), T-cell receptor varible transcripts as disease related markers.
Bonini, Maria Chiara; Genovese, Pietro; Gregory, Philip D.; Holmes, Michael C.; Naldini, Luigi; Paschon, David; Provasi, Elena; Zhang, Lei, Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases.
Finn, Olivera J.; Alajez, Nehad M.; Schmielau, Jan; Alter, Mark D., Therapeutic and diagnostic cloned MHC-unrestricted receptor specific for the MUC1 tumor associated antigen.
Steven W. Brostoff ; Darcy B. Wilson ; Lawrence R. Smith ; Daniel P. Gold ; Dennis J. Carlo, Vaccination and methods against multiple sclerosis resulting from pathogenic responses by specific T cell populations.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.