T-cell receptor-deficient T cell compositions
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12N-005/10
C12N-005/0783
A61K-035/17
A61K-035/12
출원번호
US-0383662
(2016-12-19)
등록번호
US-9822340
(2017-11-21)
발명자
/ 주소
Sentman, Charles L.
출원인 / 주소
THE TRUSTEES OF DARTMOUTH COLLEGE
대리인 / 주소
Teskin, Robin L.
인용정보
피인용 횟수 :
0인용 특허 :
44
초록▼
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. An isolated primary human T cell or progeny thereof, which: (i) has been modified to functionally impair and/or to reduce expression of the endogenous T cell receptor (TCR), and(ii) has been further modified to express at least one functional exogenous non-TCR chimeric receptor comprising a ligan
1. An isolated primary human T cell or progeny thereof, which: (i) has been modified to functionally impair and/or to reduce expression of the endogenous T cell receptor (TCR), and(ii) has been further modified to express at least one functional exogenous non-TCR chimeric receptor comprising a ligand binding domain attached to a signaling domain. 2. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the expression of the endogenous TCR is reduced. 3. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the endogenous TCR is functionally impaired. 4. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the impaired endogenous TCR of the isolated modified primary human T cell or progeny thereof elicits a reduced graft versus host disease response against allogeneic (HLA-mismatched) cells compared to a human T cell which expresses the same endogenous TCR but which endogenous TCR is not impaired. 5. The isolated modified primary human T cell or progeny thereof of claim 2, wherein the impaired endogenous TCR elicits a reduced graft versus host disease response against allogeneic (HLA-mismatched) cells compared to a human T cell which expresses the same endogenous TCR but which endogenous TCR is not impaired. 6. The isolated modified primary human T cell or progeny thereof of claim 3, wherein the impaired endogenous TCR elicits a reduced graft versus host disease response against allogeneic (HLA-mismatched) cells compared to a human T cell which expresses the same endogenous TCR but which endogenous TCR is not impaired. 7. The isolated modified primary human T cell or progeny thereof of claim 1, which does not elicit a GVHD response in a histoincompatible human recipient. 8. The isolated modified primary human T cell or progeny thereof of claim 2, which does not elicit a GVHD response in a histoincompatible human recipient. 9. The isolated modified primary human T cell or progeny thereof of claim 3, which does not elicit a GVHD response in a histoincompatible human recipient. 10. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the chimeric receptor comprises a NKG2D, NKG2A, NKG2C, NKG2F, LLT1, AICL, CD26, or NKRP1 polypeptide. 11. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the chimeric receptor binds to tumor cells. 12. The isolated modified primary human T cell or progeny thereof of claim 11, wherein the ligand binding domain of said chimeric receptor is obtained from an anti-tumor chimeric antigen receptor or anti-tumor antibody. 13. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the non-TCR chimeric receptor comprises a receptor that binds to MIC-A, MIC-B, estrogen, progesterone, RON, or one or more members of the ULBP/RAET1 family. 14. The isolated modified primary human T cell or progeny thereof of claim 13, wherein the one or more members of the ULBP/RAET1 family is/are selected from the group consisting of ULBP2, ULBP3, Rae-1, H-60, HCMV UL18, or Rae-1β. 15. The isolated modified primary human T cell or progeny thereof of claim 1, which are derived from T cell or primary human PBMCs of a human subject. 16. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the modified T cell expresses CD4. 17. The isolated modified primary human T cell or progeny thereof of claim 1, wherein the modified T cell expresses CD8. 18. The isolated modified primary human T cell of claim 1, which is capable of differentiating into a T regulatory cell. 19. A composition suitable for use in human therapy, comprising a therapeutically effective amount of isolated modified primary human T cells according to claim 1 or progeny thereof and at least one pharmaceutically acceptable carrier. 20. The composition of claim 19, which is useful in treating histoincompatible (non-HLA matched) human subjects, wherein histoincompatibility is based on the HLA allotype of the administered isolated primary human T cells. 21. The composition of claim 19 which is suitable for use in the treatment of cancer.
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.