Universal anti-CD22 chimeric antigen receptor engineered immune cells
Inventors
Smith, Julianne • Duchateau, Phillippe • DERRIEN, Murielle
Assignees
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Publication Number
US-12133867-B2
Publication Date
2024-11-05
Expiration Date
Abstract
The present invention relates to an engineered immune cell endowed with CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.
Core Innovation
The invention describes an engineered human Universal Chimeric Antigen Receptor (CAR) T Cell specific for CD22 (UCART22) that comprises an anti-CD22 CAR and a safety switch. The anti-CD22 CAR comprises amino acid residues 22-490 of SEQ ID NO: 15, and the safety switch comprises a sequence of SEQ ID NO: 60.
The UCART22 further comprises an inactivated CD52 gene and an inactivated T cell receptor alpha constant (TRAC) gene. In certain embodiments, both alleles of the CD52 gene and both alleles of the TRAC gene are inactivated, and the genome comprises a polynucleotide with SEQ ID NO: 11 inserted and an inactivated TRAC gene with an insertion, deletion, or mutation within a sequence of SEQ ID NO: 18.
The disclosure characterizes UCART22 by undetectable levels of TCR expression on the cell surface as measured by flow cytometry. The overall concept is directed to treating cancer in a subject in need thereof by administering the engineered UCART22 T cell, where the anti-CD22 CAR design and safety switch sequence are defined and where CD52 and TRAC are inactivated.
Claims Coverage
The claim coverage includes two independent claims: one directed to an engineered UCART22 CAR T cell and one directed to a method of treating cancer by administering UCART22. Across these independent claims, the coverage centers on defined anti-CD22 CAR components, a defined safety switch sequence, and inactivated CD52 and TRAC genes, with dependent refinements to allele-level inactivation and characterization.
Universal cd22-specific car t cell with defined anti-cd22 car sequence
An engineered human Universal Chimeric Antigen Receptor (CAR) T Cell specific for CD22 (UCART22) comprising a chimeric antigen receptor specific for CD22 (anti-CD22 CAR) wherein the anti-CD22 CAR comprises amino acid residues 22-490 of SEQ ID NO: 15.
Safety switch with defined SEQ ID NO: 60 sequence
An engineered human UCART22 wherein a safety switch comprises a sequence of SEQ ID NO: 60.
Inactivated CD52 gene and inactivated TRAC gene
An engineered human UCART22 comprising an inactivated CD52 gene and an inactivated T cell receptor alpha constant (TRAC) gene.
Administering UCART22 to treat cancer in a subject
A method of treating a cancer in a subject in need thereof comprising administering an engineered human UCART22 that comprises an anti-CD22 CAR and a safety switch, wherein the anti-CD22 CAR comprises amino acid residues 22-490 of SEQ ID NO: 15 and the safety switch comprises a sequence of SEQ ID NO: 60, and wherein the UCART22 comprises an inactivated CD52 gene and an inactivated TRAC gene.
The claim coverage is anchored on UCART22 cells that combine a CD22-specific CAR defined by residues 22-490 of SEQ ID NO: 15, a safety switch defined by SEQ ID NO: 60, and a genetic design including inactivated CD52 and inactivated TRAC. The method claim corresponds to administering this specific UCART22 construct to treat cancer.
Stated Advantages
Documented Applications
Treating cancer in a subject in need thereof by administering an engineered UCART22 CAR T cell specific for CD22.
Treating cancer that is refractory or that relapses as B-ALL.
Providing a pharmaceutical composition comprising the UCART22 and a pharmaceutically acceptable excipient.
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