TARGETING MODULES FOR UNIVERSAL CHIMERIC ANTIGEN RECEPTOR EXPRESSING IMMUNE CELLS AND USE IN THE TREATMENT OF CANCER INFECTIONS AND AUTOIMMUNE DISORDERS

• US 20200131262A1
• Filed: 06/08/2018
• Published: 04/30/2020
• Est. Priority Date: 06/09/2017
• Status: Active Grant

• Current Assignee: Avencell Europe GmbH
• Original Assignee: Gemoab Monoclonals Gmbh
• Inventors: EHNINGER, Armin
• Granted Patent: US 11,560,426 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/515 Animal cells
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/105 Bombesin; Related peptides
• CPC Class Codes: A61K 38/1883 Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• CPC Class Codes: A61K 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/31 Somatostatins
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: C07K 14/55 IL-2
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 19/00 Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/53 : Hinge
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/33 : fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies

Abstract

The present invention relates to a targeting module comprising a chemically synthesized peptide binding moiety specific for a human cell surface protein or protein complex, a kit comprising the targeting module and a vector or a cell comprising a nucleic acid encoding a universal chimeric antigen receptor and the use for the treatment of cancer, infections and autoimmune disorders.

Claims

1. A targeting module comprising a chemically synthesized peptide binding moiety specific for a human cell surface protein or protein complex, and a tag, wherein the tag is a peptide from a protein, wherein the targeting module is a peptide comprising 10 to 120 amino acids, wherein the chemically synthesized peptide binding moiety is selected from somatostatin and somatostatin analogues, somatostatin antagonists, bombesin and bombesin analogues, gastrin-releasing peptide (GRP) and GRP analogues, neuromedin B and neuromedin B analogues, vasoactive secretin family, glutamate-urea-lysine motif, melanocyte-stimulating hormones (MSH) and MSH analogues, cholecystokinins (CCK), gastrins, neurotensin and neurotensin analogues, gonadotropin-releasing hormone family, neurokines, exendins or exenatides, Arg-Gly-Asp (RGD) peptides and Asn-Gly-Arg (NGR) peptides, neuregulins or wherein the chemically synthesized peptide binding moiety has binding specificity to membrane receptors.

2. The targeting module according to claim 1, wherein the tag is a peptide from a human protein.

3. The targeting module according to claim 1, wherein the tag is a peptide from a human nuclear protein.

4. The targeting module according to claim 1, wherein the chemically synthesized peptide binding moiety is selected from somatostatin, bombesin, gastrin-releasing peptide (GRP), vasoactive intestinal peptide (VIP), glutamate-urea-lysine motif, α

-melanocyte-stimulating hormone (α

-MSH), melanotan 2 (α

-M2), cholecystokinin (CCK), gastrin, neurotensin, neuropeptide Y, luteinizing hormone-releasing hormone (LHRH), substance P, Exendin, Arg-Gly-Asp (RGD) peptide, Asn-Gly-Arg (NGR) peptides.

5. The targeting module according to claim 1, wherein the chemically synthesized peptide binding moiety comprises at least two peptides selected from somatostatin and somatostatin analogue, somatostatin antagonists, bombesin and bombesin analogues, gastrin-releasing peptide (GRP) and GRP analogues, glutamate-urea-lysine motif, neuromedin B and neuromedin B analogues, vasoactive secretin family, melanocyte-stimulating hormones (MSH) and MSH analogues, cholecystokinins (CCK), gastrins, neurotensin and neurotensin analogues, gonadotropin-releasing hormone family, neurokines, exendins or exenatides, Arg-Gly-Asp (RGD) peptides and Asn-Gly-Arg (NGR) peptides, neuregulins or wherein the chemically synthesized peptide binding moiety has binding specificity to membrane receptors.

6. The targeting module according to claim 1, wherein the chemically synthesized peptide binding moiety and/or the tag comprise D amino acids, pseudo peptide bonds, amino alcohols, non-proteinogenic amino acids, amino acids with modified side chains and/or the chemically synthesized peptide binding moiety and/or the tag are circularized peptides.

7. The targeting module according to claim 1, wherein the tag is a peptide from human nuclear La protein.

8. The targeting module according to claim 1 according to SEQ. ID NO. 26, Formula (I) or Formula (II).

9. The targeting module according to claim 1, further comprising a chelator.

10. A method for the treatment of cancer, infection, or an inflammatory or autoimmune disorder comprising administering to a patient the targeting module according to claim 1.

11. A kit comprising

a) a targeting module according to claim 1 and

b) a vector or a cell comprising a nucleic acid encoding a universal chimeric antigen receptor,

wherein the universal chimeric antigen receptor comprises three domains,

wherein

the first domain is a tag-binding domain,

the second domain is an extracellular hinge and a transmembrane domain and

the third domain is a signal transduction domain,

wherein tag-binding domain binds to the tag of the targeting module according to claim 1.

12. The kit according to claim 11, wherein tag-binding domain binds to a tag from a human nuclear La protein.

13. The kit according to claim 11, wherein the extracellular hinge and transmembrane domain is selected from hinge and transmembrane domains of human CD28 molecule, CD8a chain NK cell receptors;

or parts of the constant region of an antibody and combinations thereof.

14. The kit according to claim 11, wherein the signal transduction domain is selected from cytoplasmic regions of CD28, CD137 (4-1BB), CD134 (OX40), DAP10 and CD27, programmed cell death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), cytoplasmic regions of CD3 chains, DAP12 and activating Fc receptors.

15. The kit according to claim 11, wherein the nucleic acid is SEQ. ID NO. 1, 9, 13 or 16 encoding for a universal chimeric antigen receptor with an amino acid sequence according to SEQ. ID NO. 17, 18, 19 or 20.

16. A pharmaceutical composition comprising a targeting module according to claim 1.

17. The targeting module according to claim 7, wherein the tag is a short linear epitope from the human nuclear La protein according to SEQ. ID NO. 25 or SEQ. ID NO. 27.

18. The kit according to claim 12, wherein the tag-binding domain is an antibody or an antigen-binding fragment, wherein the tag-binding domain constitutes an anti-La epitope scFv.

19. The kit according to claim 18, wherein the tag-binding domain constitutes an anti-La epitope scFv according to SEQ. ID NOs. 21 and 22 or SEQ. ID NOs. 23 and 24.