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US 2024/0181056 A1Published application
Chimeric antigen receptor (car)-t cells
AssigneeImperial College Innovations Limited
InventorsXiaoning Xu, Weiwei Ma, Lan Zhao
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AssigneeImperial College Innovations Limited
InventorsXiaoning Xu, Weiwei Ma, Lan Zhao
Estimating the term…
The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to anti-CD4 CARs, and to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention extends to genetic constructs per se, and to their use in generating the CAR-MAIT cells, and to transduced CAR-MAIT cells per se. The invention also extends to various medical uses of the constructs and transduced CAR-MAIT cells, and to pharmaceutical compositions comprising these constructs and CAR-MAIT cells.
A nucleic acid construct comprising a promoter operably linked to a first coding sequence, which encodes an anti-CD4 chimeric antigen receptor (CAR).
A construct according to any preceding claim, wherein the promoter is a PGK promoter, optionally the promoter comprises a nucleotide sequence substantially as set out in SEQ ID No:
A construct according to any preceding claim, wherein the CAR is specific for a CD4 antigen which comprises an amino acid sequence substantially as set out in SEQ ID No:1, or a variant or fragment thereof.
A construct according to any preceding claim, wherein the first coding sequence comprises a nucleotide sequence encoding an amino acid sequence substantially as set out in SEQ ID No:6, or a fragment or variant thereof;
A construct according to any preceding claim, wherein the first coding sequence comprises a nucleotide sequence encoding an amino acid sequence substantially as set out in SEQ ID No:8, or a fragment or variant thereof;
A construct according to any preceding claim, wherein the construct comprises a nucleotide sequence encoding a CD8a hinge and transmembrane (TM) structure domain.
A construct according to any preceding claim, wherein the construct comprises a nucleotide sequence encoding an intracellular domain, which comprises a signalling domain of CD28, a signalling domain of 4-1BB and/or a CD3ζ chain, and more preferably a signalling domain of CD28, a signalling domain of 4-1BB and a CD3ζ chain.
A construct according to any preceding claim, wherein the nucleic acid construct comprises a second coding sequence, which encodes at least one suicide protein, and more preferably at least two suicide proteins.
A construct according to any preceding claim, wherein the construct comprises a nucleotide sequence encoding an amino acid sequence substantially as set out in SEQ ID No:
A construct according to any preceding claim, wherein the construct comprises a nucleotide sequence substantially as set out in SEQ ID No:
The T-cell according to either claim 23 or 24, or the pharmaceutical composition according to claim 25, for use according to claim 41, wherein:
Dependencies are inferred from the claim text.