JPWO2020146413A5 - - Google Patents

Claims (32)

An isolated anti-Labyrintin construct comprising an antibody portion that specifically binds to Labyrintin or a portion thereof and an effector domain. 2. The isolated anti-Labyrintin construct of Claim 1, wherein the antibody portion is conjugated to an effector domain. 3. The isolated anti-Labyrintin construct of Claim 2, wherein the effector domain comprises an effector molecule. 4. The isolated anti-Labyrintin construct of claim 3, wherein the effector molecule comprises a therapeutic agent. 5. The isolated anti-Labyrintin construct of Claim 4, wherein the therapeutic agent is selected from the group consisting of drugs, toxins, radioisotopes, proteins, peptides, and nucleic acids. 6. The isolated anti-Labyrintin construct of any one of claims 1-5, wherein the isolated anti-Labyrintin construct is an antibody drug conjugate (ADC). 4. The isolated anti-Labyrintin construct of Claim 3, wherein the effector domain comprises a diagnostic agent. 8. The isolated anti-Labyrintin construct of Claim 7, wherein the diagnostic agent is a label. 2. The isolated anti-Labyrintin construct of Claim 1, wherein the antibody portion is fused to an effector domain. The isolated anti-labyrintin construct is a chimeric antigen receptor (CAR) comprising an extracellular domain comprising an antibody portion fused to an effector domain, wherein the effector domain comprises a transmembrane domain and an intracellular signaling domain. 10. The isolated anti-Labyrintin construct of claim 9, comprising: 10. The isolation of claim 9, wherein the isolated anti-labyrintin construct is a bispecific T cell engager (BiTE) comprising an extracellular domain comprising an antibody portion fused to an anti-CD3 antibody or fragment thereof. Anti-Labyrintin Constructs. The isolated anti-labyrintin construct is a T-cell receptor (TCR) comprising an extracellular domain comprising an antibody portion fused to an effector domain, wherein the effector domain comprises the transmembrane domain of the TCR subunit and/or or an intracellular signaling domain. 13. The isolated anti-Labyrintin of any one of claims 1-12, wherein the antibody portion is a full length antibody, Fab, Fab', (Fab')2, Fv, or a single chain Fv (scFv). construction. 14. The isolated anti-Labyrintin construct of any one of claims 1-13, wherein the antibody portion binds Labyrintin or a portion thereof with a Kd of about 0.1 pM to about 500 nM. 15. The isolated anti-Labyrintin construct of any one of claims 1-14, wherein the antibody portion specifically binds to a Labyrintin-derived peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:2-32. . 16. The isolated anti-Labyrintin construct of claim 15, wherein the Labyrintin-derived peptide comprises a B-cell epitope. 17. The isolated anti-Labyrintin construct of claim 15 or 16, wherein the Labyrintin-derived peptide comprises a T-cell epitope. 18. The isolated anti-Labyrintin construct of any one of claims 1-17, wherein the antibody portion is multispecific. Multispecific antibody moieties include tandem scFv, diabodies (Db), single chain diabodies (scDb), dual affinity retargeting (DART) antibodies, dual variable domain (DVD) antibodies, knobs into holes ( KiH) antibody, Dock and Lock (DNL) antibody, chemically crosslinked antibody, heteromultimeric antibody, or heteroconjugate antibody. 20. The isolated anti-Labyrintin construct of Claim 19, wherein the multispecific antibody portion is a tandem scFv comprising two scFvs linked by an optional peptide linker. 21. A pharmaceutical composition comprising the isolated anti-Labyrintin construct of any one of claims 1-20. 21. A host cell expressing the isolated anti-Labyrintin construct of any one of claims 1-20. 21. A nucleic acid encoding a polypeptide component of the isolated anti-Labyrintin construct of any one of claims 1-20. 24. An effector cell comprising the nucleic acid of claim 23. 25. The effector cell of claim 24, wherein the effector cell is a T cell. A method for detecting a cell displaying labyrintin or a portion thereof on its surface, comprising:
(a) contacting a cell with the isolated anti-Labyrintin construct of claim 8; and (b) detecting the presence of a label on the cell. A composition for treating an individual with a Labyrintin-positive disease, comprising:
(a) an effective amount of the pharmaceutical composition of claim 21; or (b) an effective amount of the effector cells of claim 24 or 25.
A composition comprising : 28. The composition of claim 27, wherein labyrintin status is used as a criterion for selecting individuals for treatment. A method of diagnosing an individual with a Labyrintin-positive disease comprising:
(a) administering to the individual an effective amount of the isolated anti-Labyrintin construct of claim 8; and (b) determining the level of label in the individual, wherein the level exceeds a threshold level. A method comprising determining that the level of label indicates that the individual has a Labyrintin-positive disease. A method of diagnosing an individual with a Labyrintin-positive disease comprising:
(a) contacting a sample from the individual with the isolated anti-Labyrintin construct of any one of claims 1-20; and (b) with the isolated anti-Labyrintin construct in the sample. A method comprising identifying one or more bound cells, thereby diagnosing an individual with a Labyrintin-positive disease. 31. The composition or method of any one of claims 26-30 , wherein the Labyrintin-positive disease is Labyrintin-positive cancer. 32. The composition or method of claim 31, wherein the Labyrintin-positive cancer is adenocarcinoma.