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US 12,624,081 B2Granted
Tn-MUC1 chimeric antigen receptor (CAR) T cell therapy
AssigneeThe Trustees of the University of Pennsylvania
InventorsAvery D. Posey, Carl H. June
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Abstract
Various TnMUC1-specific chimeric antigen receptors (CARs), nucleic acids encoding the same, and methods of using the same, are provided. Compositions and methods comprising a TnMUC1-specific CAR for treating MUC1-associated cancer in a subject in need thereof are provided.
Claims14
A modified immune cell comprising:
- (a) a chimeric antigen receptor (CAR) that specifically binds MUC1 on a target cell, wherein the CAR comprises a MUC1-specific antigen binding domain, a transmembrane domain, a costimulatory signaling domain, and an intracellular signaling domain of CD3 zeta, and wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO:
- 47;
- and
- (b) a switch receptor comprising an extracellular domain of a signaling protein associated with a negative signal, a transmembrane domain, and an intracellular domain of a signaling protein associated with a positive signal;
- wherein the extracellular domain and the intracellular domain are respectively selected from PD-1 and CD28, PD-1A132L and CD28, PD-1 and 4-1BB, PD-1A132L and 4-1BB, PD-1 and IL12Rβ1, PD-1A132L and IL12Rβ1, PD-1 and IL12Rβ2, PD-1A132L and IL12Rβ2, TGFβRII and IL12Rβ1, TGFβRII and IL12Rβ2, TGFβRII and CD28, or TIM3 and CD28;
- and
- wherein the switch receptor is able to switch a negative signal to a positive signal upon activation, thereby enhancing an immune response.
4 more elements
An isolated nucleic acid comprising:
- (a) a first nucleic acid sequence encoding a chimeric antigen receptor (CAR) that specifically binds MUC1 on a target cell, wherein the CAR comprises a MUC1-specific antigen binding domain, a transmembrane domain, a costimulatory signaling domain, and an intracellular signaling domain of CD3 zeta, and wherein the first nucleic acid sequence comprises SEQ ID NO:
- 46;
- and
- (b) a second nucleic acid sequence encoding a switch receptor comprising an extracellular domain of a signaling protein associated with a negative signal, a transmembrane domain, and an intracellular domain of a signaling protein associated with a positive signal;
- wherein the extracellular domain and the intracellular domain are respectively selected from PD-1 and CD28, PD-1A132L and CD28, PD-1 and 4-1BB, PD-1A132L and 4-1BB, PD-1 and IL12Rβ1, PD-1A132L and IL12Rβ1, PD-1 and IL12Rβ2, PD-1A132L and IL12Rβ2, TGFβRII and IL12Rβ1, TGFβRII and IL12Rβ2, TGFβRII and CD28, or TIM3 and CD28;
- wherein the switch receptor is able to switch the negative signal to the positive signal upon activation, thereby enhancing an immune response;
- and
- wherein the first and second nucleic acid sequences are separated by a nucleic acid sequence encoding a self-cleaving peptide.
5 more elements
Dependencies are inferred from the claim text.