Back to results
US 12,479,924 B2Granted
Constructs specifically recognizing Glypican 3 and uses thereof
AssigneeEureka Therapeutics, Inc.
InventorsPengbo Zhang, Yiyang Xu, Javier Morales, Yoko Nakano, Hong Liu, Jingyi Xiang, Timothy Acker
Life of this patent
Estimating the term…
Abstract
The present application provides constructs comprising an antibody moiety specifically recognizing Glypican 3 (GPC3), such as a cell surface-bound GPC3. Also provided are methods of making and using these constructs.
Claims27
An engineered immune cell expressing on its surface:
- a) a chimeric antibody-T cell receptor (TCR) construct (caTCR) comprising:
- i) an extracellular domain comprising an antibody moiety;
- and
- ii) a TCR module (TCRM), wherein the TCRM comprises (a) a first TCR domain (TCRD) comprising a first TCR transmembrane domain (TCR-TM), and (b) second TCRD comprising a second TCR-TM, wherein the first TCR-TM is derived from one of the transmembrane domains of a TCR and the second TCR-TM is derived from the other transmembrane domain of the TCR, and wherein the TCRM facilitates recruitment of at least one TCR-associated signaling molecule;
- wherein the caTCR lacks a functional primary immune cell signaling sequence;
- and
- b) an anti-glypican 3 (GPC3) chimeric co-stimulatory receptor (CSR) comprising:
- i) an extracellular ligand-binding module comprising an anti-GPC3 antibody moiety that specifically binds to GPC3;
- ii) a transmembrane module;
- and
- iii) an intracellular co-stimulatory immune cell signaling module;
- wherein the anti-GPC3 CSR lacks a functional primary immune cell signaling sequence;
- and
- wherein the anti-GPC3 antibody moiety of the anti-GPC3 CSR comprises:
- (1) a heavy chain complementarity determining region (HC-CDR) 1 comprising the amino acid sequence of SEQ ID NO:
- 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 54, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 105, a light chain complementarity determining region (LC-CDR) 1 comprising the amino acid sequence of SEQ ID NO:
- 156, an LC-CDR2 comprising the amino acid sequence of GDN, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 258;
- (2) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 21, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 72, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 123, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 174, an LC-CDR2 comprising the amino acid sequence of YDS, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 276;
- (3) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 24, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 75, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 126, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 177, an LC-CDR2 comprising the amino acid sequence of DDS, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 279;
- (4) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 52, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 103, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 154, an LC-CDR2 comprising the amino acid sequence of SNH, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 256;
- (5) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 11, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 62, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 113, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 164, an LC-CDR2 comprising the amino acid sequence of SNN, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 266;
- or
- (6) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 12, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 63, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 114, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 165, an LC-CDR2 comprising the amino acid sequence of SNT, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 267.
48 more elements
An engineered immune cell expressing on its surface:
- a) an anti-GPC3 caTCR comprising:
- i) an extracellular domain comprising an anti-GPC3 antibody moiety that specifically binds to GPC3;
- and
- ii) a TCRM, wherein the TCRM comprises (a) a first TCRD comprising a first TCR-TM, and (b) a second TCRD comprising a second TCR-TM, wherein the TCRM facilitates recruitment of at least one TCR-associated signaling molecule, wherein the first TCR-TM is derived from one of the transmembrane domains of a TCR and the second TCR-TM is derived from the other transmembrane domain of the TCR;
- wherein the anti-GPC3 caTCR lacks a functional primary immune cell signaling sequence;
- and
- b) a CSR comprising:
- i) an extracellular ligand-binding module;
- ii) a transmembrane module;
- and
- iii) an intracellular co-stimulatory immune cell signaling module;
- wherein the CSR lacks a functional primary immune cell signaling sequence;
- and
- wherein the anti-GPC3 antibody moiety of the anti-GPC3 caTCR comprises:
- (1) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 54, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 105, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 156, an LC-CDR2 comprising the amino acid sequence of GDN, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 258;
- (2) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 21, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 72, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 123, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 174, an LC-CDR2 comprising the amino acid sequence of YDS, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 276;
- (3) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 24, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 75, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 126, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 177, an LC-CDR2 comprising the amino acid sequence of DDS, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 279;
- (4) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 52, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 103, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 154, an LC-CDR2 comprising the amino acid sequence of SNH, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 256;
- (5) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 11, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 62, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 113, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 164, an LC-CDR2 comprising the amino acid sequence of SNN, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 266;
- or
- (6) an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 12, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 63, an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 114, an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 165, an LC-CDR2 comprising the amino acid sequence of SNT, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 267.
48 more elements
Dependencies are inferred from the claim text.