Compositions and methods for treating cancer with anti-CD33 immunotherapy
AssigneesLentigen Technology, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsRimas Orentas, Dina Schneider, Boro Dropulic, Dimiter S. Dimitrov, Zhongyu Zhu
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Abstract
Chimeric antigen receptors containing CD33 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.
Claims15
An isolated chimeric antigen receptor (CAR) comprising, from N terminus to C-terminus:
- (i) at least one extracellular antigen binding domain that binds to CD33 comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:2 or SEQ ID NO:4 or a single chain fragment variable (ScFv) domain selected from the group consisting of SEQ ID NO:
- 6, 8, 10 and 12;
- (ii) a transmembrane domain comprising a transmembrane domain of a protein selected from the group consisting of the T-cell receptor (TCR) alpha chain, the TCR beta chain, the TCR zeta chain, CD28, CD3 epsilon, CD45, CD4, CDS, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154, or any combination thereof;
- (iii) at least one costimulatory domain comprising a functional signaling domain selected from the group consisting of OX40, CD70, CD27, CD28, CDS, ICAM-1, LFA-1 (CD111a/CD18), ICOS (CD278), DAP10, DAP12, and 4-1BB (CD137), or any combination thereof;
- and
- (iv) an intracellular signaling domain comprising a functional domain selected from the group consisting of a 4-1BB (CD137);
- CD28, and CD3 zeta signaling domain, or a combination thereof.
A method of making a cell comprising transducing a T cell with a vector comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR) comprising, from N-terminus to C-terminus:
- (i) at least one extracellular antigen binding domain that binds to CD33 comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:2 or SEQ ID NO:4 or a single chain fragment variable (ScFv) domain selected from the group consisting of SEQ ID NO:
- 6, 8, 10 and 12;
- (ii) a transmembrane domain comprising a transmembrane domain of a protein selected from the group consisting of the T-cell receptor (TCR) alpha chain, the TCR betachain, the TCR zeta chain, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154, or any combination thereof;
- (iii) at least one costimulatory domain comprising a functional signaling domain selected from the group consisting of OX40, CD70, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), DAP10, DAP12, and 4-1BB (CD137), or any combination thereof;
- and
- (iv) an intracellular signaling domain comprising a functional domain selected from the group consisting of a 4-1BB (CD137), CD28, and CD3 zeta signaling domain, or a combination thereof.
A method of generating a population of RNA-engineered cells comprising introducing an in vitro transcribed RNA or synthetic RNA into a cell, where the RNA encodes a chimeric antigen receptor (CAR) comprising, from N-terminus to C-terminus:
- (i) at least one extracellular antigen binding domain that binds to CD33 comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:2 or SEQ ID NO:4 or a single chain fragment variable (ScFv) domain selected from the group consisting of SEQ ID NO:
- 6, 8, 10 and 12;
- (ii) a transmembrane domain comprising a transmembrane domain of a protein selected from the group consisting of the T-cell receptor (TCR) alpha chain, the TCR betachain, the TCR zeta chain, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154, or any combination thereof;
- (iii) at least one costimulatory domain comprising a functional signaling domain selected from the group consisting of OX40, CD70, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), DAP10, DAP12, and 4-1BB (CD137), or any combination thereof;
- and
- (iv) an intracellular signaling domain comprising a functional domain selected from the group consisting of a 4-1BB (CD137), CD28, and CD3 zeta signaling domain, or a combination thereof.
Dependencies are inferred from the claim text.