Bispecific antibody molecules with antigen-transfected T-cells and their use in medicine

Patent metadata

Field	Value
Publication number	US-11732052-B2
Application number	US-202016838979-A
Country	US
Kind code	B2
Filing date	Apr 2, 2020
Priority date	Feb 3, 2012
Publication date	Aug 22, 2023
Grant date	Aug 22, 2023

Abstract

Provided is a bispecific (monoclonal) antibody molecule with a first binding domain binding an antigen on CD8+ T-cells that does not naturally occur in and/or on CD8+ T-cells and a second binding domain binding to a tumor specific antigen naturally occurring on the surface of a tumor cell. The bispecific (monoclonal) antibody molecules are particularly useful in combination with transduced CD8+ T-cells comprising an antigen which does not naturally occur in and/or on CD8+ T-cells and/or a T-cell receptor. The (bispecific) antibody molecules can be used in a method for the treatment of particular diseases, wherein the (bispecific) antibody molecules are administered in combination with transduced CD8+ T-cells comprising an antigen which does not naturally occur in and/or on CD8+ T-cells and/or a T-cell receptor in a specific treatment regimen.

First claim

The invention claimed is:

1. A kit comprising
(A) a bispecific antibody molecule which comprises
(i) a first binding domain comprising a variable heavy chain (VH) and a variable light chain (VL) which binds an antigen on CD8+ T-cells that does not naturally occur in or on CD8+ T-cells, wherein the antigen is selected from the group consisting of cripto, a member of a non-T-cell cluster of differentiation (CD) family, EGFR, and TSH-R; and
(ii) a second binding domain comprising a VH and a VL which binds a tumor-specific antigen naturally occurring on the surface of a tumor cell, wherein the antigen is selected from the group consisting of EpCAM, HER-1, HER-2, HER-3, CD20, CD22, CD33, CD52, CA-12-5, HLA-DR, MUC-1 (mucin), A33-antigen, PSMA (prostate specific membrane antigen), Transferrin-receptor, Tenascin, and CA-IX; and
(B) a vector comprising a nucleic acid sequence encoding the antigen that does not naturally occur in or on CD8+ T-cells for transducing CD8+ T-cells obtained from a subject to be treated for a cancer, wherein cells of the cancer express the tumor-specific antigen naturally occurring on their surface; and
(C) instructions for use; wherein the bispecific antibody is to be administered to a subject to be treated for a cancer before, simultaneously with, or after administration of the transduced CD8+ T-cells comprising the antigen that does not naturally occur in or on CD8+ T-cells; wherein the CD8+ T-cells were obtained from the subject to be treated for a cancer; wherein cells of the cancer express the tumor-specific antigen naturally occurring on their surface.

2. The kit of claim 1 , wherein said bispecific antibody comprises a full antibody, a F(ab)-, Fab′-SH-, Fv-, scFv-, Fab′-, F(ab′)2-fragment, a chimeric antibody, a CDR-grafted antibody, a fully human antibody, a bivalent antibody-construct, an antibody-fusion protein, a synthetic antibody, a bivalent antibody, a trivalent antibody, a tetravalent antibody, a bivalent single chain antibody, a trivalent single chain antibody, or a multivalent single chain antibody.

3. The kit of claim 1 , wherein said first binding domain and/or second binding domain is human and/or humanized.

4. The kit of claim 1 , wherein the transduced CD8+ T-cells further comprise a T-cell receptor that naturally occurs on said T-cells and/or a T-cell receptor that has been genetically introduced into said T-cells.

5. The kit of claim 1 , wherein the bispecific antibody molecule is encoded by a nucleic acid sequence.

6. The kit of claim 1 , wherein the member of the non-T-cell CD family is selected from the group consisting of CD9, CD10, CD11, CD12, CD13, CD14, CD15, CD16, CD17, CD18, CD19, CD20, CD21, CD22, CD23, CD24, CD26, CD29, CD31, CD32, CD33, CD34, CD35, CD36, CD37, CD38, CD39, CD40, CD41, CD43, CD46, CD48, CD49, CD50, CD51, CD54, CD55, CD56, CD59, CD61, CD63, CD64, CD66, CD67, CD68, CD70, CD72, CD74, CD75, CD76, CD77, CD79, CD81, CD82, CD83, CD84, CD87, CD88, CD89, CD90, CD91, CD92, CD93, CD94, CD95, CD97, CD98, CD99, CD100, CD101, CD102, CD103, CD104, CD105, CD106, CD107, CD108, CD109, CD110, CD111, CD112, CD113, CD114, CD115, CD116, CD117, CD118, CD119, CD121, CD123, CD124, CD125, CD126, CD130, CD131, CD133, CD134, CD135, CD136, CD137, CD138, CD140, CD141, CD142, CD143, CD144, CD146, CD147, CD148, CD151, CD153, CD155, CD156, CD157, CD158, CD159, CD160, CD161, CD162, CD163, CD164, CD166, CD167, CD168, CD169, CD170, CD171, CD172, CD177, CD178, CD179, CD180, CD181, CD182, CD183, CD184, CD185, CD186, CD191, CD192, CD193, CD200, CD201, CD204, CD206, CD207, CD208, CD209, CD217, CD218, CD220, CD221, CD222, CD223, CD224, CD225, CD226, CD227, CD228, CD230, CD231, CD232, CD233, CD234, CD236, CD238, CD239, CD241, CD242, CD243, CD244, CD246, CD248, CD249, CD252, CD253, CD254, CD256, CD257, CD258, CD261, CD262, CD263, CD264, CD265, CD266, CD267, CD268, CD269, CD270, CD271, CD276, CD277, CD280, CD281, CD282, CD283, CD284, CD286, CD288, CD289, CD290, CD292, CD294, CD295, CD296, CD297, CD298, CD299, CD300, CD301, CD302, CD303, CD304, CD305, CD306, CD309, CD312, CD314, CD315, CD316, CD317, CD318, CD319, CD320, CD321, CD322, CD324, CD325, CD326, CD327, CD328, CD329, CD331, CD332, CD333, CD334, CD335, CD336, CD337, CD338, CD339, CD340, CD344, CD349, CD350, CD351, CD352, CD353, CD354, CD355, CD357, CD358, CD360, CD361, CD362 and CD363.

7. A bispecific antibody which comprises
(i) a first binding domain comprising a VH and a VL which binds an antigen on CD8+ T-cells that does not naturally occur in or on CD8+ T-cells, wherein the antigen is selected from the group consisting of cripto, a member of a non-T-cell cluster of differentiation (CD) family, EGFR and TSH-R; and
(ii) a second binding domain comprising a VH and a VL which binds a tumor-specific antigen naturally occurring on the surface of a tumor cell, wherein the antigen is selected from the group consisting of EpCAM, HER-1, HER-2, HER-3, CD20, CD22, CD33, CD52, CA-12-5, HLA-DR, MUC-1 (mucin), A33-antigen, PSMA (prostate specific membrane antigen), Transferrin-receptor, Tenascin, and CA-IX;
wherein said bispecific antibody is to be administered to a subject to be treated for a cancer before, simultaneously with, or after administration of transduced CD8+ T-cells comprising said antigen which does not naturally occur in or on CD8+ T cells, and wherein said CD8+ T-cells were obtained from the subject to be treated for a cancer, wherein cells of the cancer express the tumor-specific antigen naturally occurring on their surface.

8. The bispecific antibody of claim 7 , wherein the cancer is selected from cancer of epithelial, endothelial or mesothelial origin and cancer of the blood.

9. The bispecific antibody of claim 7 , wherein said bispecific antibody comprises a full antibody, a F(ab)-, Fab′-SH-, Fv-, scFv-, Fab′-, F(ab)2-fragment, a chimeric antibody, a CDR-grafted antibody, a fully human antibody, a bivalent antibody-construct, an antibody-fusion protein, a synthetic antibody, a bivalent antibody, a trivalent antibody, a tetravalent antibody, bivalent single chain antibody, a trivalent single chain antibody, or a multivalent single chain antibody.

10. The bispecific antibody of claim 7 , wherein said first binding domain and/or second binding domain is human and/or humanized.

11. The bispecific antibody of claim 7 , wherein the transduced CD8+ T-cells further comprises a T-cell receptor that naturally occurs on said T-cells and/or a T-cell receptor that has been genetically introduced into said T-cell.

12. The bispecific antibody of claim 7 , wherein the bispecific antibody is encoded by a nucleic acid sequence.

13. The bispecific antibody of claim 7 , wherein the member of the non-T-cell CD family is selected from the group consisting of CD9, CD10, CD11, CD12, CD13, CD14, CD15, CD16, CD17, CD18, CD19, CD20, CD21, CD22, CD23, CD24, CD26, CD29, CD31, CD32, CD33, CD34, CD35, CD36, CD37, CD38, CD39, CD40, CD41, CD43, CD46, CD48, CD49, CD50, CD51, CD54, CD55, CD56, CD59, CD61, CD63, CD64, CD66, CD67, CD68, CD70, CD72, CD74, CD75, CD76, CD77, CD79, CD81, CD82, CD83, CD84, CD87, CD88, CD89, CD90, CD91, CD92, CD93, CD94, CD95, CD97, CD98, CD99, CD100, CD101, CD102, CD103, CD104, CD105, CD106, CD107, CD108, CD109, CD110, CD111, CD112, CD113, CD114, CD115, CD116, CD117, CD118, CD119, CD121, CD123, CD124, CD125, CD126, CD130, CD131, CD133, CD134, CD135, CD136, CD137, CD138, CD140, CD141, CD142, CD143, CD144, CD146, CD147, CD148, CD151, CD153, CD155, CD156, CD157, CD158, CD159, CD160, CD161, CD162, CD163, CD164, CD166, CD167, CD168, CD169, CD170, CD171, CD172, CD177, CD178, CD179, CD180, CD181, CD182, CD183, CD184, CD185, CD186, CD191, CD192, CD193, CD200, CD201, CD204, CD206, CD207, CD208,

Assignees

• Hoffmann La Roche
• Ludwig Maximilians Univ Munchen

Inventors

• Bourquin Carole
• Castoldi Raffaella
• Endres Stefan
• Klein Christian
• Kobold Sebastian
• Niederfellner Gerhard
• Sustmann Claudio

Classifications

• A61K40/4254

  Adhesion molecules, e.g. NRCAM, EpCAM or cadherins · CPC title

• A61K40/4204

  Epidermal growth factor receptors [EGFR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title