Ultramodular igg3-based spacer domain and multi-function site for implementation in chimeric antigen receptor design

Abstract

To provide immunotherapy using immune cells such as chimeric antigen receptor (CAR)-engineered T cells.SOLUTION: The present invention relates to immunotherapy using chimeric antigen receptor (CAR)-engineered T cells that carry a novel, IgG3-Hinge-based spacer domain, allowing a finely modulated response to target antigens.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention generally relates to immunotherapy using immune cells such as chimeric antigen receptor (CAR)-modified T cells. In particular, the present invention relates to immunotherapy using chimeric antigen receptor (CAR)-modified T cells having a novel IgG3 hinge-based spacer domain that allows for a finely tuned response to a target antigen. Further, the present invention relates to introducing one or more IgG3 hinge-based multifunctional sites (MFSs) into CARs and other immune receptors to enable purification, stimulation, expansion, and exhaustion of CAR T cells. The present invention also includes antibody sequences that target this motif and enable the performance of the aforementioned functions.

Background Art

[0002] A chimeric antigen receptor (CAR) is a synthetic immune receptor developed to redirect T cells to recognize surface antigens on tumor cells. In its most basic format, a CAR contains the variable heavy and variable light chains of a monoclonal antibody (in cis, i.e., as a single-chain variable fragment, scFv) fused to a transmembrane domain and the signaling domain of CD3ζ 1 . A way to improve this basic CAR design was to include a spacer domain located between the scFv and the transmembrane domain to provide range and flexibility to promote antigen binding by the CAR 2 . Eventually, several spacer domains were used in CAR constructs containing Fc regions and immunoglobulin-like domains derived from IgG1 and IgG4, IgD, CD4, CD7, CD8α, and CD28 3-6 .

[0003] Conventional approaches in this field involve using a single spacer design for all CAR constructs, even if they can recognize different epitopes of a given antigen or different antigens ("one CAR must fit all"). However, since CARs bind to surface antigens on tumor cells, the spatial requirements for optimal antigen binding and optimal interaction between CAR-modified T cells and tumor cells can vary depending on the epitope and target antigen. Thus, the conventional approach of using a single spacer design for all epitopes and antigens seems simplistic and suboptimal. If there is suboptimal CAR binding and / or suboptimal interaction between CAR-modified T cells and tumor cells, subsequent CAR-T cell stimulation and anti-tumor responses may also be suboptimal. 3、7 To increase the opportunity to achieve more optimized CAR-target molecule interactions, the inventors previously studied variants of IgG4-derived spacers with different lengths and compositions. The emerging paradigm was that there is a correlation between spacer length and efficacy, such that membrane-proximal epitopes of target cells are better reached by CARs containing longer spacers, and membrane-distal epitopes are better reached by CARs containing shorter spacers. 7 Based on the structure of the IgG4 molecule, three IgG4 hinge-based spacer variants of different sizes by >100 aa are available (IgG4_short: IgG4 hinge, 12 aa; IgG4_middle: IgG4 hinge + C H 3, 119 aa; IgG4_long: IgG4 hinge + CH2 + CH3, 228 aa) 7 .

[0004] Among all human IgG molecules, IgG3 exhibits the highest Fab-Fab folding flexibility and Fab-Fc folding flexibility. In contrast to all other immunoglobulins, the structure of IgG3 as a hinge is unique and incorporates three copies of a 15 aa motif due to exon duplication. 8-11Naturally occurring variants of IgG3 that have only one or two copies of this motif in the hinge region exhibit much shorter Fab-to-Fc distances (45 Å and 65 Å compared to 105 Å). 8 These stepwise differences, along with the opportunity to extend and shorten the spacer region by addition or removal of one or more copies of this 15-aa motif, allowed the present invention to construct an IgG3 hinge library by taking advantage of the ability to finely tune the length of the spacer for each target. Furthermore, the inventors have identified monoclonal antibodies specific for the IgG3 central hinge motif, enabling the use of additional CAR-specific functions that are antigen-independent but include purification, stimulation, expansion, and exhaustion of CAR T cells. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEMS

[0005] The present invention generally relates to immunotherapy using immune cells such as chimeric antigen receptor (CAR)-modified T cells. In particular, the present invention relates to immunotherapy using chimeric antigen receptor (CAR)-modified T cells having a novel IgG3 hinge-based spacer domain that allows for a finely tuned response to a target antigen. Furthermore, the present invention relates to introducing one or more IgG3 hinge-based multifunctional sites (MFS) into CARs and other immune receptors to enable purification, stimulation, expansion, and exhaustion of CAR T cells. The present invention also includes antibody sequences that target this motif and enable the performance of the aforementioned functions.

[0006] The present invention particularly provides the following items and is characterized by the following items. 1. An immune receptor comprising one or more IgG3 central hinge repeat domain motifs, wherein the immune receptor does not include an IgG3 CH2 and / or CH3 domain. 2. [A - B n (wherein A is the amino acid sequence of SEQ ID NO: 2, ​B is the IgG3 central hinge domain repeat motif, and the motif has the amino acid sequence of SEQ ID NO: 1, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5) The immunoreceptor according to item 1, comprising an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, or most preferably 100% sequence identity with the amino acid sequence of 3. [A - B n The immunoreceptor according to item 2, comprising an amino acid sequence having 100% sequence identity with the amino acid sequence of 4. The immunoreceptor according to item 2 or 3, wherein n is an integer between 1 and 10. 5. The immunoreceptor according to item 2 or 3, wherein n is an integer between 1 and 5. 6. The immunoreceptor according to item 2 or 3, wherein n is an integer between 3 and 5. 7. An extracellular antigen - binding domain, a spacer domain, a transmembrane domain, and an intracellular signaling domain and the spacer domain is located between the extracellular antigen - binding domain and the transmembrane domain, Optionally, the spacer domain contains one or more IgG3 central hinge domain repeat motifs. The immunoreceptor according to any one of items 1 to 6. 8. The immunoreceptor according to item 7, wherein both the transmembrane domain and the intracellular domain consist of a sequence selected from the group consisting of SEQ ID NOs: 109, 110, 111, 112, 113, 114, 115, and 174. 9. An extracellular antigen - binding domain comprising a first domain, a linker, and optionally, a second domain and optionally, the linker is located between the first domain and the second domain, ​ The immune receptor according to any one of items 1 to 8, wherein optionally the linker comprises one or more IgG3 central hinge domain repeat motifs. 10. The spacer domain comprises one or more IgG3 central hinge domain repeat motifs, and / or the linker comprised in the extracellular antigen-binding domain comprises one or more IgG3 central hinge domain repeat motifs, The immune receptor according to item 7, 8 or 9. 11. The immune receptor according to any one of items 1 to 10, selected from the group consisting of a T cell receptor (TCR), preferably a recombinant TCR; a B cell receptor (BCR), preferably a recombinant BCR; and a chimeric antigen receptor (CAR). 12. The immune receptor comprises an antigen-binding domain, I) the first domain comprises a heavy chain variable domain, II) the first domain comprises a light chain variable domain, III) the first domain comprises a heavy chain variable domain and the second domain comprises a light chain variable domain, IV) the first domain comprises a heavy chain variable domain and the second domain comprises a heavy chain variable domain, or V) the first domain comprises a light chain variable domain and the second domain comprises a light chain variable domain, the immune receptor according to any one of items 9 to 11. 13. The immune receptor comprises an antigen-binding domain, and the antigen-binding domain comprises a first domain, a linker, and a second domain, which is part of a single-chain variable fragment (scFv), The scFv optionally comprises, as the heavy chain / light chain variable sequences comprised in the first / second domain, the following antigens: A) CD19, optionally, i) the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 27, The light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 28, the scFv can specifically bind to CD19, or ii) the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 27 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 28; B) CD20, optionally, i) the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 30, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 29, the scFv can specifically bind to CD20, or ii) the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 30 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 29; C) ROR1, optionally, i) respectively, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 31, 33, 35, or 37, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 32, 34, 36, or 38, the scFv can specifically bind to ROR1, or ii) respectively, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 31, 33, 35, or 37 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 32, 34, 36, 38; D) ROR2, optionally, i) the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 39, The light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 40, the scFv can specifically bind to ROR2, or ii) the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 39 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 40; E) SLAMF7, optionally, i) each, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 41 or 43, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 42 or 44, the scFv can specifically bind to SLAMF7, or ii) each, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 41 or 43 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 42 or 44; F) FLT3, optionally, i) each, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 45 or 47, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 46 or 48, the scFv can specifically bind to FLT3, or ii) each, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 45 or 47 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 46 or 48; G) Siglec-6, optionally, i) the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 49, The light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 50, the scFv is capable of specifically binding to Siglec-6, or ii) the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 49 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 50; H) α v β3 integrin, optionally, i) each, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 51 or 53, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 52 or 54, the scFv is capable of specifically binding to α v β3 integrin, or ii) each, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 51 or 53 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 52 or 54; or I) BCMA, optionally, i) each, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 55 or 57, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 56 or 58, the scFv is capable of specifically binding to BCMA, or ii) each, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 55 or 57 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 56 or 58 An immunoreceptor according to any one of items 9 to 12, comprising the heavy chain / light chain variable sequences of an scFv specific for one of the above. 14. The immune receptor comprises an antigen-binding domain, and the antigen-binding domain is: I) an scFv specific for CD19, optionally, the scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 3 or 71 and can specifically bind to CD19, or the scFv has the amino acid sequence of SEQ ID NO: 3 or 71; II) an SCFV specific for CD20, optionally, the scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 4 or 72 and can specifically bind to CD20, or the scFv has the amino acid sequence of SEQ ID NO: 4 or 72; III) an scFv specific for ROR1, optionally, the scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 5, 6, 7, 8, 73, 74, 75, 76, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100 and can specifically bind to ROR1, or the scFv has the amino acid sequence of SEQ ID NO: 5, 6, 7, 8, 73, 74, 75, 76, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100; IV) an scFv specific for ROR2, optionally, the scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 9, 77, 101, 102, 103, 104, 105, 106, 107 or 108 and can specifically bind to ROR2, or the scFv has the amino acid sequence of SEQ ID NO: 9, 77, 101, 102, 103, 104, 105, 106, 107 or 108; V) An scFv specific for SLAMF7, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 10, 11, 78 or 79, and can specifically bind to SLAMF7, or said scFv has the amino acid sequence of SEQ ID NO: 10, 11, 78 or 79; VI) An scFv specific for FLT3, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 12, 13, 80 or 81, and can specifically bind to FLT3, or said scFv has the amino acid sequence of SEQ ID NO: 12, 13, 80 or 81; VII) An scFv specific for Siglec-6, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 14 or 82, and can specifically bind to Siglec-6, or said scFv has the amino acid sequence of SEQ ID NO: 14 or 82; VIII) α v An scFv specific for β3 integrin, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 15, 16, 83 or 84, and can specifically bind to α v β3 integrin, or said scFv has the amino acid sequence of SEQ ID NO: 15, 16, 83 or 84; IX) An scFv specific for BCMA, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 17, 18, 85 or 86, and can specifically bind to BCMA, or said scFv has the amino acid sequence of SEQ ID NO: 17, 18, 85 or 86 The immune receptor according to any one of items 9 to 13, comprising 15. The immune receptor according to any one of items 1 to 14, which is a chimeric antigen receptor (CAR). 16. One or more IgG3 central hinge domain repeat motifs are I) derived from the human IgG3 central hinge and / or II) consist of the amino acid sequence of SEQ ID NO: 1 and / or III) have reduced immunogenicity compared to repeats of the IgG1 hinge domain and / or IgG4 hinge domain, the immunoreceptor or CAR according to any one of items 1 to 15. 17. I) does not include all or part of the lower hinge domain sequence of the human IgG3 hinge domain, II) [A - B n (wherein A is the amino acid sequence of SEQ ID NO: 2, B is the IgG3 central hinge domain repeat motif, the motif having the amino acid sequence of SEQ ID NO: 1, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5) and an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, or most preferably 100% sequence identity, III) contains the IgG3 central hinge domain repeat motif 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times and / or IV) has reduced immunogenicity compared to a second CAR that is different from the first CAR in that it does not contain the one or more IgG3 central hinge domain repeat motifs, the immunoreceptor or CAR according to any one of items 1 to 16. 18. The immunoreceptor or CAR according to any one of items 1 to 17, comprising at least two, preferably at least three, of the IgG3 central hinge domain repeat motifs adjacent to each other. ​19. The CAR according to any one of items 1 to 18, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, and 171. 20. A nucleic acid encoding the immune receptor or CAR according to any one of items 1 to 19. 21. A cell comprising the nucleic acid according to item 20. 22. I) The cell is an immune cell, preferably a B cell, macrophage, NK cell or T cell, more preferably a T cell, even more preferably a CD4 + and / or CD8 + T cell, II) The cell expresses the immune receptor or CAR according to any one of items 1 to 19, III) The cell contains a nucleic acid stably integrated into the genome, and / or IV) The nucleic acid contained in the cell is contained in an episomal vector, the cell according to item 21. 23. The nucleic acid, cell containing the nucleic acid, immune receptor, or CAR according to any one of items 1 to 22, for use in a method of treating cancer, autoimmune disease, infectious disease, or degenerative disease. 24. The disease is cancer, the cancer is a hematological cancer or a solid cancer, Optionally, the hematological cancer is leukemia or lymphoma, preferably acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, Burkitt lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, or diffuse large B-cell lymphoma, Optionally, the solid cancer is breast cancer, colon cancer, lung cancer, pancreatic or prostate cancer or glioblastoma, the immune receptor, CAR, nucleic acid or cell containing the nucleic acid for use according to item 23. 25. An antigen-binding protein, streptamer, or aptamer that can bind to an epitope contained by a sequence consisting of at least one, preferably at least two, more preferably at least three repeats of the amino acid sequence of SEQ ID NO: 1, and optionally, at least two repeats are adjacent to each other. 26. The antigen-binding protein, streptamer, or aptamer according to item 25, which can bind to the immune receptor or CAR according to any one of items 1 to 19. 27. The antigen-binding protein, streptamer, or aptamer according to item 26, which can stimulate the immune receptor or CAR according to any one of items 1 to 19. 28. The antigen-binding protein, streptamer, or aptamer according to any one of items 25 to 27, which is an antigen-binding protein that is an antibody or a fragment thereof, preferably a monoclonal antibody or a fragment thereof. 29. a) A heavy chain variable region having at least 80%, preferably at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 19, preferably containing a CDR1 having the amino acid sequence of SEQ ID NO: 20, a CDR2 having the amino acid sequence of SEQ ID NO: 21, and a CDR3 having the amino acid sequence of SEQ ID NO: 22, b) A light chain variable region having at least 80%, preferably at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 23, preferably containing a CDR1 having the amino acid sequence of SEQ ID NO: 24, a CDR2 having the amino acid sequence of SEQ ID NO: 25, and a CDR3 having the amino acid sequence of SEQ ID NO: 26 The antigen-binding protein according to any one of items 25 to 28, comprising. 30. Use of the antigen-binding protein, streptamer, or aptamer according to any one of items 25 to 29 for purification, detection, depletion, stimulation, expansion, or enrichment of cells expressing the immune receptor or CAR according to any one of items 1 to 19. 31. A method comprising the step of binding an antigen-binding protein, streptamer or aptamer to a cell expressing an immunoreceptor or CAR according to any one of items 1 to 19, preferably, the binding is specific binding to the IgG3 central hinge repeat domain contained in the immunoreceptor or CAR, and / or the antigen-binding protein, streptamer or aptamer is an antigen-binding protein, streptamer or aptamer according to any one of items 25 to 29, said method. 32. A method for purifying a cell expressing an immunoreceptor or CAR according to any one of items 1 to 19, A) Optionally obtaining a cell expressing a chimeric antigen receptor; B) Incubating the cell with a primary antibody, streptamer or aptamer which is the antigen-binding protein, streptamer or aptamer according to any one of items 25 to 29, under conditions that allow an antibody, streptamer or aptamer to bind to the immunoreceptor or CAR expressed by the cell; C) Separating antibody-bound cells, streptamer-bound cells or aptamer-bound cells from unbound cells to obtain purified cells The method according to item 31, said method comprising the above steps. 33. Step C includes incubating the cells of step B with an entity capable of binding to an antibody, streptamer or aptamer, I) The entity is more preferably a fluorescent marker; or preferably a secondary antibody labeled with beads, more preferably magnetic beads, II) The primary antibody, streptamer or aptamer is labeled, and the label is preferably a tag or a fluorescent dye, III) The separation in step C is carried out by means of MACS or FACS, and / or IV) The separation is carried out using a streptamer or aptamer, The purification method according to item 32. 34. A method for depleting a cell expressing an immunoreceptor or CAR according to any one of items 1 to 19, A) Optionally obtaining cells expressing an immune receptor or a CAR; B) incubating the cells with an antigen-binding protein, streptamer or aptamer according to any one of items 25 to 29 bound to a cytotoxic molecule; The method according to item 31, which is the method described above and includes the above steps. 35. A method for a) stimulating and / or b) expanding cells expressing an immune receptor or a CAR according to any one of items 1 to 19, comprising: A) Optionally obtaining cells expressing an immune receptor or a CAR; B) Optionally incubating the cells with an antigen-binding protein, streptamer or aptamer according to any one of items 25 to 29, wherein the antigen-binding protein, streptamer or aptamer is bound to a solid phase or expressed on the surface of the cells; The method according to item 31, which is the method described above and includes the above steps. 36. I) The solid phase is a tissue culture surface or beads, preferably magnetic beads, and / or II) The solid phase is a scaffold made of a polymer, preferably starch or sugar. The stimulation or expansion method according to item 35. 37. A method for concentrating cells expressing an immune receptor or a CAR according to any one of items 1 to 19, comprising: A) Stimulating and / or expanding the cells by the method according to item 35 or 36; B) Purifying the cells from step A by the method according to item 32 or 33. The method according to item 31, which is the method described above and includes the above steps. 38. The method or use according to any one of items 30 to 37, which is an in vitro method or use. 39. The method or use according to any one of items 30 to 38, which does not include a method for treating the body of a human or animal by surgery or therapy, or a diagnostic method performed on the body of a human or animal. 40. A pharmaceutical composition comprising a cell expressing an antigen-binding protein, streptamer or aptamer according to any one of items 25 to 29, or a chimeric antigen receptor comprising all or part of said antigen-binding protein, streptamer or aptamer, said composition optionally further comprising a pharmaceutically acceptable carrier and / or excipient. 41. A cell expressing an antigen-binding protein, streptamer or aptamer according to any one of items 25 to 29, or a chimeric antigen receptor comprising all or part of said antigen-binding protein, streptamer or aptamer, or the pharmaceutical composition according to item 40, wherein the antigen-binding protein, streptamer or aptamer bound to a cytotoxic molecule, or the cell expressing the chimeric antigen receptor comprising all or part of said antigen-binding protein, streptamer or aptamer, is administered to a subject in need thereof, for use in the treatment of cell depletion of an immunoreceptor or CAR according to any one of items 1 to 19, said antigen-binding protein, streptamer or aptamer, or said cell, or said pharmaceutical composition. 42. A kit comprising an immunoreceptor or CAR according to any one of items 1 to 19 and an antigen-binding protein, streptamer or aptamer according to any one of items 25 to 27. 43. A bispecific antibody comprising one or more IgG3 central hinge repeat domain motifs. 44. The bispecific antibody according to item 43, wherein one or more IgG3 central hinge domain repeat motifs are I) derived from the human IgG3 central hinge, and / or II) consist of the amino acid sequence of SEQ ID NO: 1, and / or III) have reduced immunogenicity compared to repeats of the IgG1 hinge domain and / or IgG4 hinge domain. 45. I) does not contain all or part of the sequence of the lower hinge domain of the human IgG3 hinge domain, II) [A - B n ​(wherein A is the amino acid sequence of SEQ ID NO: 2, B is the IgG3 central hinge domain repeat motif, and the motif has the amino acid sequence of SEQ ID NO: 1, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5) and comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, or most preferably 100% sequence identity with the amino acid sequence of III) contains the IgG3 central hinge domain repeat motif 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times, and / or IV) has reduced immunogenicity compared to a second bispecific antibody that is different from the first bispecific antibody in that it does not contain one or more of the IgG3 central hinge domain repeat motifs. The bispecific antibody according to item 43 or 44. 46. The immune receptor contains an amino acid sequence having 100% sequence identity with the amino acid sequence of [A-B n . The bispecific antibody according to any one of items 43 to 45. 47. The bispecific antibody according to item 45 or 46, wherein n is an integer between 1 and 10. 48. The immune receptor according to item 45 or 46, wherein n is an integer between 1 and 5. 49. The immune receptor according to item 45 or 46, wherein n is an integer between 3 and 5. 50. The bispecific antibody according to any one of items 43 to 49, which contains at least two, preferably at least three IgG3 central hinge repeat domain motifs, and optionally, at least two of the IgG3 central hinge repeat domain motifs are adjacent to each other. 51. The immune receptor, CAR, nucleic acid, cell, method, pharmaceutical composition, kit, or bispecific antibody according to any one of items 1 to 24 or 31 to 50, wherein the IgG3 central hinge repeat domain motif is not the mouse IgG3 central hinge repeat domain.

Brief Description of Drawings

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Mode for Carrying Out the Invention

[0008] Over the past few decades, the design of chimeric antigen receptors (CARs) (previously also called T-Bodies) has evolved from rather simple constructs to more complex molecules assembled from different protein domains. In its simplest form today, which is also called first-generation CAR, the CAR consisted of the scFv of a monoclonal antibody fused to the signaling domain of the CD3ζ subunit. 1 Subsequently, it became clear that most CAR constructs require a spacer between the scFv and the transmembrane domain to induce full T cell effector function. 2。From the mid-1990s to the present, the Fc region or immunoglobulin-like domain has been derived from different proteins (including CD4, CD7, CD8α, CD28, IgD, IgG1 and IgG4, with the CD8α hinge being the most commonly used and most well-studied one 3-6 ), but most researchers in the field have used a format with only one spacer in all of their CAR constructs. This has yielded effective results, although the CAR designs used may not always be the most functional. Different antibodies bind to different epitopes on their target molecules. The inventors have shown in previous studies that spacers with compositions and lengths adjusted to optimally fit the target epitope result in the greatest antitumor function 7 。

[0009] The present invention provides a novel variant of the hinge domain of human IgG3 for incorporation into a genetically modified immune receptor, for example, as a spacer domain in a CAR construct.

[0010] The inventors generated a library of CARs with IgG3-derived spacers in which the scFv and transmembrane domain were linked by variants of the human IgG3 hinge domain. This naturally consists of an upper hinge (12aa, ELKTPLGDTTHT, SEQ ID NO: 2), a central hinge (50aa, CPRCP, SEQ ID NO: 59 + a 15aa motif EPKSCDTPPPCPRCP, 3 repeats of SEQ ID NO: 1) and a lower hinge (8aa, APELLGGP, SEQ ID NO: 60), and this wild-type spacer, called IgG3_UMLH (upper, central and lower hinges), results in a total spacer size of 70aa. Since the inventors constructed variants consisting of the upper hinge (ELKTPLGDTTHT, SEQ ID NO: 2), 0 to 10 copies of the n-terminal portion of the central hinge (CPRCP, SEQ ID NO: 59) and the EPKSCDTPPPCPRCP motif (SEQ ID NO: 1) resulted in spacer domains ranging from 17 to 167aa in 15aa steps, designated IgG3_MiH0 to IgG3_MiH10.

[0011] Other researchers have previously practiced the CH2-CH3 hinge version of IgG3 as a spacer domain in CAR designs 12、13 In contrast to the present invention, these researchers used two lengths of variants in which the upper hinge (ELKTPLGDTTHT, SEQ ID NO: 2) and the beginning of the central hinge (CPRCP, SEQ ID NO: 59) were removed, but instead the IgG3 CH2 and CH3 domains were additionally used. These two versions, called CH2-CH3-hinge and CH2-CH3-hinge-hinge, are both much longer (232aa or 247aa), have an FC binding motif that can cause immunogenicity, and include relatively rigid CH2 and CH3 regions, and thus are much less flexible than any of the variants included in the present inventors' IgG3 spacer library 12、13 。

[0012] The inventors' data show that the optimal IgG3 spacer conformation can be generated for each target investigated as a sweet spot depending on the position of the scFv epitope within the target molecule. The general principle is that for epitopes located distally to the tumor membrane, shorter variants result in the most potent T cell effector functions, while for epitopes located proximally to the membrane, longer variants result in better functions. Generally, the inventors show that IgG3-based spacers inherit excellent flexibility that exceeds the flexibility of other formats. In particular, CARs with a relatively short IgG3-based spacer of only 62aa (IgG3_MiH3) are superior to the IgG4 variant that shows best functionality with a very long spacer of 228aa, thereby reducing the size of the CAR and the gene cargo that has to be delivered. The reduction of the gene cargo is associated with several beneficial effects such as improved transfection or transduction efficiency, improved genetic safety, and enabling the use of vectors limited to a certain maximum size. For potent scFvs such as the CD19-specific scFv FMC63, the inventors show that most variants function substantially and that optimized versions of the IgG3 spacer are equally effective in inducing proliferation, cytokine secretion, and cytotoxicity. For most other targets, the optimal conformation that results in the best anti-tumor efficacy can be identified, both in vitro and in vivo.

[0013] The inventors identified an antibody called anti-MiH antibody #1 that can specifically bind to the IgG3 central hinge region, but their data suggest that proper binding requires three or more IgG3_MiH repeats. Using this antibody and its derivatives, the inventors were able to show that CAR T cells can be targeted specifically to the CAR but are antigen-independent. The inventors have revealed that additional functions that can be exploited include the stimulation, expansion, exhaustion, and enrichment of CAR T cells directly via the CAR itself instead of a CAR-independent transduction marker.

[0014] Since our data suggest that the majority of CAR scFvs exhibit optimal function with a somewhat short spacer that truncates below the three IgG3_MiH repeats, we included a second multifunctional site containing five IgG3_MiH repeats between the first and second domains of the scFv, thereby replacing the commonly used (G4S)3 linker.

[0015] We show that this alternative linker between scFv V H and V L does not impair target recognition of the CAR construct and enables the utilization of additional functions. Our data demonstrate that targeting of the multifunctional site results in efficient, antigen-independent but CAR-specific stimulation and proliferation of CAR T cells, as well as specific enrichment and depletion.

[0016] In previous attempts, StrepTag II was used as part of the spacer and as a tag 14 or the myc tag was used as part of the spacer domain and as a tag 15 . In contrast, the concept we provide is derived from fully human proteins in their unmodified form and results in far less immunogenicity development than can occur with such artificial proteins. Furthermore, it has not been shown that for these tags, several copies of the motif can be successively placed to optimize spacer length and flexibility.

[0017] In summary, our data encourage the use of IgG3 hinge-derived spacer domains for implementation in CAR design. Their excellent functionality related to the antigen-independent but CAR-specific utilization of spacer-targeted antibodies with low immunogenicity of the CAR construct makes this approach an attractive option for preclinical, clinical, and commercial use.

[0018] Definitions and Embodiments Unless otherwise defined specifically below, the terms used in the present invention shall be understood in accordance with the general meanings known to those skilled in the art.

[0019] Each publication, patent application, patent, and other reference cited in this specification is incorporated by reference in its entirety to the extent not inconsistent with the present invention. References are indicated by reference numbers and the corresponding reference details provided in the "References" section.

[0020] The IgG3 central hinge domain repeat motif according to the present invention is a motif located in the central hinge of an antibody of the IgG3 class and can occur two or more times in the hinge region. In a preferred embodiment, the IgG3 central hinge domain repeat motif is identical to the amino acid sequence of SEQ ID NO: 1.

[0021] The immune receptor according to the present invention is a transmembrane receptor and can mediate an immune response when expressed by immune cells. The immune receptor may be an endogenous immune receptor or a non-natural immune receptor, i.e., it may be genetically modified. Exemplary immune receptors according to the present invention are the B cell receptor (BCR), the T cell receptor (TCR), and the chimeric antigen receptor (CAR). The monomeric form of the immune receptor may consist of a single molecule containing all of its domains or a heterodimer containing all of its domains. The immune receptor may bind directly to its antigen or indirectly through an adapter.

[0022] The immune receptor according to the present invention may include an antigen-binding domain including a first domain, a linker, and optionally a second domain. The first and second domains are not limited to a specific molecular orientation, that is, either the first domain or the second domain can be located at the N-terminus or C-terminus of each other. Optionally, the second domain may be absent, that is, the antigen-binding domain may consist of the first domain and the linker in any orientation with respect to the N-terminal or C-terminal orientation. An exemplary embodiment of the antigen-binding domain is a single-chain variable fragment (scFv). In this case, the first domain may include a light-chain variable domain or a heavy-chain variable domain linked by a peptide linker, and the second domain may include a light-chain variable domain or a heavy-chain variable domain linked by a peptide linker. Either the first domain or the second domain may be located at either the N-terminus or the C-terminus of the scFv.

[0023] In one embodiment, the immune receptor can bind to an antigen, preferably a cancer antigen, more preferably a cancer cell surface antigen. In a preferred embodiment, the immune receptor can bind to the extracellular domain of a cancer antigen. In a preferred embodiment, the immune receptor is a chimeric antigen receptor. In a preferred embodiment, the immune receptor is a genetically modified T cell receptor.

[0024] In a preferred embodiment, the immune receptor is expressed in T cells. In a preferred embodiment of the present invention, the immune receptor is expressed in T cells, and the T cells can specifically bind to antigen-expressing cancer cells with high specificity so as to exert a growth inhibitory effect, preferably a cytotoxic effect, on the cancer cells.

[0025] In a preferred embodiment according to the present invention, immune cells are isolated from a healthy donor or a patient having cancer and are transduced with a gene transfer vector encoding an immunoreceptor comprising one or more IgG3 central hinge repeat domain motifs capable of binding to an antigen expressed by the cancer, and are administered to a patient for treating the cancer. In a preferred embodiment, the immune cells are B cells, NK cells, macrophages or T cells. In a more preferred embodiment, the T cells are CD8+ T cells or CD4+ T cells.

[0026] As used herein, the term antibody refers to any functional antibody capable of specifically binding to a target antigen. Without particular limitation, the term antibody encompasses antibodies from any suitable source species, including birds such as chickens and mammals such as mice, goats, rabbits, non-human primates and humans. Preferably, the antibody is a humanized antibody. A humanized antibody is an antibody containing human sequences and a small portion of non-human sequences that confer binding specificity for a target antigen (e.g., human FLT3). The antibody is preferably a monoclonal antibody that can be prepared by methods well known in the art. The term antibody encompasses IgG-1, -2, -3, or -4, IgE, IgA, IgM, or IgD isotype antibodies. The term antibody encompasses monomeric antibodies (IgD, IgE, IgG, etc.) or oligomeric antibodies (IgA or IgM, etc.). The term antibody also encompasses, without particular limitation, isolated antibodies and genetically modified antibodies, such as chimeric antibodies or bispecific antibodies and other modified antibodies.

[0027] An antibody fragment or a fragment of an antibody, as used herein, refers to a part of an antibody that retains the ability of the antibody to specifically bind to an antigen (e.g., the IgG3 central hinge repeat domain). This ability can be determined, for example, by determining the ability of an antigen-binding portion that competes with the antibody for specific binding to the antigen by methods known in the art. Without particular limitation, antibody fragments can be produced by any suitable method known in the art, including preparation by recombinant DNA methods and chemical or enzymatic fragmentation of antibodies. Antibody fragments can be Fab fragments, F(ab') fragments, F(ab')2 fragments, single-chain antibodies (scFv), single-domain antibodies, diabodies, or any other part of an antibody that retains the ability of the antibody to specifically bind to an antigen.

[0028] The "antibodies" (e.g., monoclonal antibodies) or "fragments thereof" described herein may be derivatized or linked to different molecules. For example, molecules that can be linked to an antibody are other proteins (e.g., other antibodies), molecular labels (e.g., fluorescent, luminescent, colored or radioactive molecules), pharmaceuticals and / or toxins. The antibody or antigen-binding portion may be linked directly (e.g., in the form of a fusion between two proteins) or via a linker molecule (e.g., any suitable type of chemical linker known in the art).

[0029] A "bispecific antibody" is an antibody or a fragment thereof described herein that can specifically bind to two different antigens. Exemplary embodiments of bispecific antibodies are antibodies that can specifically bind to a cancer cell surface antigen (e.g., CD19 or CD20) and an immune cell surface antigen (e.g., CD3). Bispecific antibodies preferably can recruit immune cells to target cells such as cancer cells, thereby mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Bispecific antibodies may include a portion that interacts with an Fc receptor.

[0030] The terms "treatment of cancer" or "treating cancer" according to the present invention refer to therapeutic treatment. Evaluation of whether a therapeutic treatment can be effective can be made, for example, by evaluating whether the treatment inhibits cancer growth in the treated patient. Preferably, the inhibition is statistically significant when evaluated by an appropriate statistical test known in the art. Inhibition of cancer growth can be evaluated by comparing cancer growth in a group of patients treated according to the present invention with an untreated patient control group, or by comparing a group of patients receiving a standard cancer treatment in the art plus treatment according to the present invention with a patient control group receiving only a standard cancer treatment in the art. Such tests for evaluating inhibition of cancer growth are designed according to criteria acceptable for clinical trials, for example, double-blind, randomized trials having sufficient statistical power. The term "treating cancer" includes inhibition of cancer growth where cancer growth is partially inhibited (i.e., cancer growth in the patient is retarded compared to the patient control group), inhibition where cancer growth is completely inhibited (i.e., cancer growth in the patient stops), and inhibition where cancer growth is reversed (i.e., the cancer shrinks). Evaluation of whether a therapeutic treatment is effective can be made based on known clinical indicators of cancer progression.

[0031] Treatment of cancer according to the present invention does not exclude that additional or secondary therapeutic benefits may also occur to the patient. For example, the additional or secondary benefit may be enhancement of engraftment of transplanted hematopoietic stem cells performed before, simultaneously, or after treatment of cancer. However, it is understood that the main treatment for which protection is sought is for treating the cancer itself, and any secondary or additional benefits only reflect optional additional advantages of treating cancer growth.

[0032] Treatment of cancer according to the present invention may be first-line treatment, second-line treatment, third-line treatment, or fourth-line treatment. The treatment may also be a treatment beyond fourth-line treatment. The meanings of these terms are known in the art and follow the terminology generally used by the National Cancer Institute of the United States.

[0033] The treatment of infectious diseases, autoimmune diseases, and degenerative diseases may each be a first-line treatment, second-line treatment, third-line treatment, or fourth-line treatment. The treatment may also be a treatment beyond fourth-line treatment. The meanings of these terms are known in the art.

[0034] As used herein, the term "capable of binding" refers to the ability to form a complex with a molecule to be bound (e.g., IgG3 central hinge repeat domain). Binding typically occurs non-covalently by intermolecular forces such as ionic bonds, hydrogen bonds, and van der Waals forces, and is typically reversible. Various methods and assays for determining binding ability are known in the art. Binding is usually high-affinity binding, and the affinity when measured by the KD value is preferably less than 1 μM, more preferably less than 100 nM, even more preferably less than 10 nM, even more preferably less than 1 nM, even more preferably less than 100 pM, even more preferably less than 10 pM, and even more preferably less than 1 pM.

[0035] As used herein, each time a term such as "comprising" or "comprises" appears, it may optionally be replaced with "consisting of" or "consists of".

[0036] As used herein, terms such as "linker" containing "one or more IgG3 central hinge domain repeat motifs" or "spacer domain" containing "one or more IgG3 central hinge domain repeat motifs" can refer to a linker or spacer domain in which the one or more IgG3 central hinge domain repeat motifs are present in addition to the one or more IgG3 central hinge domain repeat motifs of the immune receptor of the present invention. Alternatively, terms such as "linker" containing "one or more IgG3 central hinge domain repeat motifs" or "spacer domain" containing "one or more IgG3 central hinge domain repeat motifs" can refer to a linker or spacer domain in which the one or more IgG3 central hinge domain repeat motifs are identical to the one or more IgG3 central hinge domain repeat motifs of the immune receptor of the present invention.

[0037] The term "reduction of immunogenicity" associated with an immune receptor or CAR or bispecific antibody should be understood according to its general meaning in the art. In a preferred embodiment according to all other embodiments of the present invention, "reduction of immunogenicity" associated with an immune receptor or CAR means that the immune receptor or CAR is expressed in an HLA / A2 positive tumor cell line, and then the cell line is co-incubated with PBMCs from an HLA / A2 positive donor, and then, in a comparison with a second immune receptor or CAR in an assay that performs an enzyme-linked immunosorbent assay (ELISA)-based determination of whether the immune receptor or CAR results in a reduction in cytokine production by PBMCs, the immune receptor or CAR has reduced immunogenicity. In a preferred embodiment according to all other embodiments of the present invention, "reduction of immunogenicity" associated with a bispecific antibody means that the bispecific antibody results in a reduction in anti-drug antibody levels in a human patient as compared to a second bispecific antibody. Anti-drug antibody levels can be determined by methods known in the art, including ELISA-based methods.

[0038] A pharmaceutically acceptable carrier comprising any suitable diluent may be used herein as is known in the art. As used herein, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a State government or listed in the U.S. Pharmacopeia, European Pharmacopeia, or other generally recognized pharmacopeias for use in mammals, more specifically in humans. Pharmaceutically acceptable carriers include, but are not limited to, physiological saline, buffered physiological saline, glucose, water, glycerol, sterile isotonic aqueous buffer solutions, and combinations thereof. It will be understood that the formulations are suitably adapted to the mode of administration.

[0039] The compositions and formulations according to the present invention are prepared according to known criteria for the preparation of pharmaceutical compositions and formulations. For example, the compositions and formulations are prepared in a manner suitable for storage and administration using pharmaceutically acceptable components such as carriers, excipients, or stabilizers. Such pharmaceutically acceptable components are not toxic in the amounts used when administering the pharmaceutical composition or formulation to a patient. The pharmaceutically acceptable components added to the pharmaceutical composition or formulation may depend on the chemical nature of the inhibitors and targeting agents present in the composition or formulation (depending on whether the targeting agent is, for example, an antibody or a fragment thereof or a cell expressing a chimeric antigen receptor), the particular intended use of the pharmaceutical composition, and the route of administration.

[0040] In a preferred embodiment according to the present invention, the composition or formulation is suitable for administration to humans, preferably the formulation is sterile and / or non-pyrogenic.

[0041] In a preferred embodiment, the present invention provides an immune receptor comprising one or more IgG3 hinge repeat domain motifs that do not contain the IgG3 CH2 and / or CH3 domains.

[0042] In an alternative embodiment, the immunoreceptor comprises an IgG3 CH2 domain. In a further alternative embodiment, the immunoreceptor comprises an IgG3 CH3 domain. In a further alternative embodiment, the immunoreceptor comprises IgG3 CH2 and CH3 domains. In a further alternative embodiment, the immunoreceptor comprises an IgG3 CH1 domain. In a further alternative embodiment, the immunoreceptor comprises IgG3 CH1, CH2 and CH3 domains.

[0043] The terms "IgG3 CH2 domain" and "IgG3 CH3 domain" should be understood according to their meanings known in the art. In a preferred embodiment according to all other embodiments of the present invention, the IgG3 CH2 domain is the CH2 domain of human IgG3 consisting of the sequence of SEQ ID NO: 172, and the IgG3 CH3 domain is the CH3 domain of human IgG3 consisting of the sequence of SEQ ID NO: 173.

[0044] In a preferred embodiment, the immune receptor according to the present invention comprises an extracellular antigen-binding domain, a spacer domain, and a transmembrane domain, and the spacer domain is located between the antigen-binding domain and the transmembrane domain. In a preferred embodiment, the spacer domain comprises one or more IgG3 central hinge domain repeat motifs. In a preferred embodiment, both the transmembrane domain and the intracellular domain of the immune receptor consist of a sequence selected from the group consisting of SEQ ID NOs: 109, 110, 111, 112, 113, 114, 115 and 174. In a preferred embodiment, the immune receptor is a chimeric antigen receptor, and the antigen-binding domain is a single-chain variable fragment linked to the chimeric antigen receptor by the spacer comprising one or more IgG3 central hinge domain repeat motifs, preferably two or more IgG3 central hinge domain repeat motifs, more preferably three or more IgG3 central hinge domain repeat motifs. In this embodiment, the antigen-binding protein (e.g., an antibody or a fragment thereof) can bind to the immune receptor by specifically binding to one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs contained in the immune receptor. The binding of the antigen-binding protein to the immune receptor by recognition of the IgG3 central hinge domain repeat motif can affect the effector function of the immune receptor, e.g., the downstream signaling that regulates the properties of the cells expressing the immune receptor, e.g., its proliferation or interaction with other immune cells. In this embodiment, the number of repeats of the IgG3 central hinge domain repeat motif contained in the spacer domain included in the immune receptor is a specific target antigen present on the surface of the target cell (e.g., CD19, CD20, ROR1, ROR2, SLAMF7, FLT3, Siglec-6, α vThe ability of the immunoreceptor to selectively and efficiently bind to β3 integrin, or BCMA, may be affected. Preferably, the target cells are cancer cells and the target antigen is a cancer antigen, i.e., a cell surface marker that is more highly expressed in cancer cells than in non-diseased cells. In an exemplary embodiment, the immunoreceptor of the present invention is a chimeric antigen receptor comprising the amino acid sequence of SEQ ID NO: 65 as a transmembrane domain. In this embodiment, the chimeric antigen receptor may further comprise a 4-1BB domain having the amino acid sequence set forth in SEQ ID NO: 66 and a CD3 zeta domain having the amino acid sequence set forth in SEQ ID NO: 67. In an exemplary embodiment, the immunoreceptor is a CD19 chimeric antigen receptor having the amino acid sequence set forth in SEQ ID NO: 68.

[0045] In another preferred embodiment, the immunoreceptor is a chimeric antigen receptor, and the antigen-binding domain is a single-chain variable fragment comprising a first domain, a linker, and a second domain. The linker comprises one or more IgG3 central hinge domain repeat motifs, preferably two or more IgG3 central hinge domain repeat motifs, more preferably three or more IgG3 central hinge domain repeat motifs. In this embodiment, the antigen-binding protein (e.g., an antibody or a fragment thereof) can bind to the immunoreceptor by specifically binding to one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs contained in the immunoreceptor. In this embodiment, the antigen-binding protein (e.g., an antibody or a fragment thereof) can bind to the immunoreceptor by specifically binding to one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs contained in the immunoreceptor. The binding of the antigen-binding protein to the immunoreceptor by recognition of the IgG3 central hinge domain repeat motif can affect the effector function of the immunoreceptor, e.g., the downstream signaling that regulates the properties of the cells expressing the immunoreceptor, e.g., its proliferation or interaction with other immune cells.

[0046] In a preferred embodiment, the presence of one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs in the immune receptor does not cause a non-specific or otherwise unwanted immunogenic reaction against cells expressing the immune receptor.

[0047] The antigen-binding domain according to the present invention can generally specifically bind to a given target antigen. In a preferred embodiment, the antigen-binding domain can specifically bind to a cell surface antigen, preferably a cancer antigen, i.e., a cell surface marker that is highly expressed in cancer cells rather than in non-diseased cells. When the antigen-binding domain is incorporated into an immune receptor according to the present invention, it enables the immune receptor to specifically recognize and bind to the target antigen to which the antigen-binding domain can specifically bind. In this embodiment, when the immune receptor containing the antigen-binding domain is expressed by a cell, the cell acquires the ability to specifically recognize target cells expressing the target antigen. In a preferred embodiment, the immune receptor is a chimeric antigen receptor and the antigen-binding domain is a single-chain variable fragment that is part of the chimeric antigen receptor.

[0048] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor comprising a spacer domain located between the extracellular antigen-binding domain and the transmembrane domain, the spacer domain comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, and the extracellular antigen-binding domain is a scFv specific for CD19, CD20, ROR1, ROR2, SLAMF7, FLT3, Siglec-6, α v β3 integrin, or BCMA, and the scFv does not contain an IgG3 central hinge domain repeat motif.

[0049] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor comprising a spacer domain located between an extracellular antigen-binding domain and a transmembrane domain, the spacer domain comprising an IgG3 central hinge domain repeat motif, and the extracellular antigen-binding domain being a scFv specific for CD19, CD20, ROR1, ROR2, SLAMF7, FLT3, Siglec-6, α v β3 integrin, or BCMA, the scFv comprising a first domain, a linker, and a second domain, the linker comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs.

[0050] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for CD19, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 27, and a light chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 28. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 27 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 28. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in the extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune reaction as compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0051] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for CD20, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 30, and a light chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 29. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 30, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 29. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in the extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not elicit a non-specific or unwanted immune response compared to a chimeric antigen receptor (not containing the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but otherwise the same, i.e., containing the same intracellular, extracellular, and transmembrane domains, and differing from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0052] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for ROR1, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 31, 33, 35, or 37, and a light chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 32, 34, 36, or 38. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 31, 33, 35, or 37, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 32, 34, 36, or 38, respectively. In this embodiment, the chimeric antigen receptor includes one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker included in an extracellular antigen-binding domain included in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune reaction as compared to a chimeric antigen receptor (not including the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but otherwise the same, i.e., including the same intracellular, extracellular, and transmembrane domains, and differing from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker included in the scFv included in the chimeric antigen receptor).

[0053] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for ROR2, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 39, and a light chain variable domain having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 40. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 39 and the light chain variable domain has the amino acid sequence of SEQ ID NO: 40. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in an extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0054] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for SLAMF7, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 41 or 43, and a light chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 42 or 44. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 41 or 43, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 42 or 44, respectively. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in an extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune reaction as compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0055] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for FLT3, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 45 or 47, and a light chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 46 or 48. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 45 or 47, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 46 or 48, respectively. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in the extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune reaction as compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0056] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for Siglec-6, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 49, and a light chain variable domain having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 50. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 49, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 50. In this embodiment, the chimeric antigen receptor includes one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker included in the extracellular antigen-binding domain included in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not include the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., includes the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker included in the scFv included in the chimeric antigen receptor).

[0057] In one embodiment, the immune receptor according to the present invention is an α vA chimeric antigen receptor specific for β3 integrin, wherein the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 51 or 53, and a light chain variable domain having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 52 or 54. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 51 or 53, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 52 or 54, respectively. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in the extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0058] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for BCMA, and the chimeric antigen receptor has a heavy chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 55 or 57, and a light chain variable domain having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 56 or 58. In one embodiment, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 55 or 57, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 56 or 58, respectively. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In one embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within the spacer domain of the chimeric antigen receptor. In another embodiment, the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs are located within a linker contained in the extracellular antigen-binding domain contained in the chimeric antigen receptor, and the extracellular antigen-binding domain is a scFv. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response as compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0059] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for CD19, and the chimeric antigen receptor comprises a scFv having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, optionally 100% sequence identity to SEQ ID NO: 3 or 71. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0060] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for CD20, and the chimeric antigen receptor has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 4 or 72, and optionally has 100% sequence identity and includes a scFv. In this embodiment, the chimeric antigen receptor includes one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker included in the extracellular antigen-binding domain included in the scFv included in the chimeric antigen receptor does not include an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not include the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., includes the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker included in the scFv included in the chimeric antigen receptor).

[0061] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for ROR1, and the chimeric antigen receptor has an scFv having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, optionally 100% sequence identity to SEQ ID NO: 5, 6, 7, 8, 73, 74, 75, 76, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response as compared to a chimeric antigen receptor (not containing the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but otherwise the same, i.e., containing the same intracellular, extracellular, and transmembrane domains and differing from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0062] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for ROR2, and the chimeric antigen receptor has an scFv having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, and optionally 100% sequence identity to SEQ ID NO: 9, 77, 101, 102, 103, 104, 105, 106, 107 or 108. In this embodiment, the chimeric antigen receptor includes one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker included in the extracellular antigen-binding domain included in the scFv included in the chimeric antigen receptor does not include an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not include the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., includes the same intracellular, extracellular, and transmembrane domains and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker included in the scFv included in the chimeric antigen receptor).

[0063] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for SLAMF7, and the chimeric antigen receptor comprises a scFv having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, optionally 100% sequence identity to SEQ ID NO: 10, 11, 78 or 79. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0064] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for FLT3, and the chimeric antigen receptor comprises a scFv having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, optionally 100% sequence identity to SEQ ID NO: 12, 13, 80 or 81. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0065] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for Siglec-6, and the chimeric antigen receptor comprises a scFv having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, and optionally 100% sequence identity to SEQ ID NO: 14 or 82. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0066] In one embodiment, the immune receptor according to the present invention is an α vA chimeric antigen receptor specific for β3 integrin, wherein the chimeric antigen receptor comprises a scFv having an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, optionally 100% sequence identity to SEQ ID NO: 15, 16, 83 or 84. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor is a chimeric antigen receptor (not containing the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but otherwise the same, i.e., containing the same intracellular, extracellular, and transmembrane domains, and differing from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor) that does not cause a non-specific or unwanted immune response as compared to the chimeric antigen receptor.

[0067] In one embodiment, the immune receptor according to the present invention is a chimeric antigen receptor specific for BCMA, and the chimeric antigen receptor comprises a scFv having an amino acid sequence with at least 80% sequence identity, preferably at least 90% sequence identity, and optionally 100% sequence identity to SEQ ID NO: 17, 18, 85 or 86. In this embodiment, the chimeric antigen receptor comprises one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs located within the spacer domain of the chimeric antigen receptor. In this embodiment, the linker contained in the extracellular antigen-binding domain contained in the scFv contained in the chimeric antigen receptor does not contain an IgG3 central hinge domain repeat motif. In a preferred embodiment, the chimeric antigen receptor does not cause a non-specific or unwanted immune response as compared to a chimeric antigen receptor (which does not contain the one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs, but is otherwise the same, i.e., contains the same intracellular, extracellular, and transmembrane domains, and differs from the chimeric antigen receptor of the present invention only in the spacer domain and / or linker contained in the scFv contained in the chimeric antigen receptor).

[0068] In another aspect, the present invention an extracellular antigen-binding domain, a spacer domain, a transmembrane domain and an intracellular signaling domain and the spacer domain is located between the extracellular antigen-binding domain and the transmembrane domain, and the spacer domain is [A - B n (wherein A is the amino acid sequence of SEQ ID NO: 2, B has the amino acid sequence of SEQ ID NO: 1, ​n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5.) The present invention also provides a chimeric antigen receptor comprising an amino acid sequence having 100% sequence identity with the amino acid sequence of .

[0069] In a preferred embodiment of this aspect, both the transmembrane domain and the intracellular domain consist of a sequence selected from the group consisting of SEQ ID NOs: 109, 110, 111, 112, 113, 114, 115 and 174.

[0070] All embodiments of the present invention as defined above for the immune receptor or CAR of the present invention are also applicable to the chimeric antigen receptor of this aspect of the present invention.

[0071] In a preferred embodiment, the chimeric antigen receptor of the present invention, which includes this aspect of the present invention, may be specific for CD19 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 3 or 71), or the chimeric antigen receptor may be specific for CD20 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 4 or 72), or the chimeric antigen receptor may be specific for ROR1 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 5, 6, 7, 8, 73, 74, 75, 76, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100), or the chimeric antigen receptor may be specific for ROR2 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 9, 77, 101, 102, 103, 104, 105, 106, 107 or 108), or the chimeric antigen receptor may be specific for SLAMF7 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 10, 11, 78 or 79), or the chimeric antigen receptor may be specific for FLT3 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 12, 13, 80 or 81), or the chimeric antigen receptor may be specific for Siglec-6 (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 14 or 82), or the chimeric antigen receptor may be specific for α v β3 integrin (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 15, 16, 83 or 84), or the chimeric antigen receptor may be specific for BCMA (wherein the extracellular antigen-binding domain includes an scFv having an amino acid sequence with 100% sequence identity to SEQ ID NO: 17, 18, 85 or 86).

[0072] In a highly preferred embodiment of the present invention, the chimeric antigen receptor of the present invention comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, and 171.

[0073] In one embodiment, an immunoreceptor according to the present invention comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs is used in therapy. In one embodiment, the present invention provides a medicament comprising, as an active ingredient, cells expressing an immunoreceptor according to the present invention, such as immune cells such as T cells.

[0074] In a preferred embodiment, a CD19-specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the CD19-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the CD19-specific chimeric antigen receptor is used in the treatment of non-Hodgkin lymphoma, multiple myeloma, Burkitt lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, and diffuse large B-cell lymphoma.

[0075] In a preferred embodiment, a CD20-specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the CD20-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the CD20-specific chimeric antigen receptor is used in the treatment of non-Hodgkin lymphoma, multiple myeloma, Burkitt lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, and diffuse large B-cell lymphoma.

[0076] In a preferred embodiment, a ROR1-specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the ROR1-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the ROR1-specific chimeric antigen receptor is used in the treatment of breast cancer, lung cancer, mantle cell lymphoma, chronic lymphocytic leukemia, and diffuse large B-cell lymphoma.

[0077] In a preferred embodiment, the ROR2-specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the ROR2-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the ROR2-specific chimeric antigen receptor is used in the treatment of breast cancer, colon cancer, prostate cancer, osteosarcoma and multiple myeloma.

[0078] In a preferred embodiment, the SLAMF7-specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the SLAMF7-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the SLAMF7-specific chimeric antigen receptor is used in the treatment of multiple myeloma, T cell and B cell leukemia, or lymphoma.

[0079] In a preferred embodiment, an FLT3 - specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the FLT3 - specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the FLT3 - specific chimeric antigen receptor is used in the treatment of acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndromes.

[0080] In a preferred embodiment, a Siglec - 6 - specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the Siglec - 6 - specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the Siglec - 6 - specific chimeric antigen receptor is used in the treatment of acute myeloid leukemia.

[0081] In a preferred embodiment, one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention are included in an α v β3 integrin - specific chimeric antigen receptor is used in the treatment of cancer, in which method the α vCells expressing a β3 integrin-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, α v The β3 integrin-specific chimeric antigen receptor is used in the treatment of breast cancer, pancreatic cancer, prostate cancer, melanoma and glioblastoma.

[0082] In a preferred embodiment, a BCMA-specific chimeric antigen receptor comprising one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs according to the present invention is used in the treatment of cancer, in which method cells expressing the BCMA-specific chimeric antigen receptor are administered to a patient in need thereof, thereby treating the cancer. In one embodiment, the cells are autologous cells, i.e., obtained from the same patient being treated. In one embodiment, the cells are allogeneic cells (since the cells are obtained from a source other than the patient being treated). In a preferred embodiment, the BCR-specific chimeric antigen receptor is used in the treatment of multiple myeloma and amyloidosis.

[0083] In one embodiment, the immunoreceptor is a T cell receptor (TCR), preferably a recombinant TCR; a B cell receptor (BCR), preferably a recombinant BCR; or a chimeric antigen receptor (CAR). In one embodiment, the immunoreceptor is a recombinant, i.e., non-natural, genetically modified T cell receptor (TCR). In one embodiment, the immunoreceptor is a recombinant, i.e., non-natural, genetically modified B cell receptor (BCR). In a preferred embodiment, the immunoreceptor is a chimeric antigen receptor (CAR).

[0084] In a preferred embodiment, the IgG3 central hinge repeat domain motif according to the present invention is derived from the human IgG3 central hinge. In a preferred embodiment, the IgG3 central hinge repeat domain motif comprises at least 10, 11, 12, 13, or 14 adjacent amino acids of SEQ ID NO: 1. In one embodiment, the IgG3 central hinge repeat domain motif comprises at least 10 adjacent amino acids of SEQ ID NO: 1. In one embodiment, the IgG3 central hinge repeat domain motif comprises at least 11 adjacent amino acids of SEQ ID NO: 1. In one embodiment, the IgG3 central hinge repeat domain motif comprises at least 12 adjacent amino acids of SEQ ID NO: 1. In one embodiment, the IgG3 central hinge repeat domain motif comprises at least 13 adjacent amino acids of SEQ ID NO: 1. In one embodiment, the IgG3 central hinge repeat domain motif comprises at least 14 adjacent amino acids of SEQ ID NO: 1. In one embodiment, the IgG3 central hinge repeat domain motif comprises at least 15 adjacent amino acids of SEQ ID NO: 1. In a preferred embodiment, the IgG3 central hinge repeat domain motif consists of the amino acid sequence of SEQ ID NO: 1 having 5, 4, 3, 2, or 1 or fewer conservative amino acid substitutions. In one embodiment, the IgG3 central hinge repeat domain motif consists of the amino acid sequence of SEQ ID NO: 1 having 5 or fewer conservative amino acid substitutions. In one embodiment, the IgG3 central hinge repeat domain motif consists of the amino acid sequence of SEQ ID NO: 1 having 4 or fewer conservative amino acid substitutions. In one embodiment, the IgG3 central hinge repeat domain motif consists of the amino acid sequence of SEQ ID NO: 1 having 3 or fewer conservative amino acid substitutions. In one embodiment, the IgG3 central hinge repeat domain motif consists of the amino acid sequence of SEQ ID NO: 1 having 2 or fewer conservative amino acid substitutions. In one embodiment, the IgG3 central hinge repeat domain motif consists of the amino acid sequence of SEQ ID NO: 1 having 1 or fewer conservative amino acid substitutions. In a preferred embodiment, the IgG3 central hinge repeat domain motif has the amino acid sequence of SEQ ID NO: 1.

[0085] In a preferred embodiment, the immune receptor according to the present invention does not include all or part of the sequence of the lower hinge domain of the IgG3 hinge domain, and preferably the IgG3 hinge domain is human.

[0086] In one embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times. In one embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 1 time. In one embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 2 times. In one embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 3 times. In one embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 4 times. In one embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 5 times. In a preferred embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif at least 3 times. In a preferred embodiment, the immune receptor according to the present invention includes the IgG3 central hinge domain repeat motif 5 times or less.

[0087] In a preferred embodiment, the immune receptor according to the present invention has an amino acid sequence of [A-Bn] (wherein A is the amino acid sequence of SEQ ID NO: 2; B is the IgG3 central hinge domain repeat motif, and the motif has the amino acid sequence of SEQ ID NO: 1; n is an integer between 1 and 15, preferably between 1 and 10, more preferably between 1 and 5, and most preferably between 3 and 5) and has at least 80% sequence identity, preferably at least 90% sequence identity, or optionally 100% sequence identity with the amino acid sequence. In one embodiment, n is 1. In one embodiment, n is 2. In one embodiment, n is 3. In one embodiment, n is 4. In one embodiment, n is 5. In a preferred embodiment, n is between 3 and 5. In a preferred embodiment, the immune receptor according to the present invention comprises at least two IgG3 central hinge domain repeat motifs adjacent to each other. In a preferred embodiment, the immune receptor according to the present invention comprises at least three IgG3 central hinge domain repeat motifs adjacent to each other.

[0088] The present invention provides a nucleic acid encoding an immune receptor according to the present invention. There are no particular restrictions on the nucleic acid of the present invention and how the nucleic acid can be expressed. For example, the nucleic acid encoding the immune receptor according to the present invention may be expressed stably or transiently. In a preferred embodiment, the nucleic acid is a viral vector. In one embodiment, the viral vector is a retroviral vector. In a preferred embodiment, the retroviral vector is a lentiviral vector. The lentiviral vector may be a first, second, third, or fourth generation lentiviral vector. Preferably, the lentiviral vector is a third or fourth generation lentiviral vector. In an exemplary embodiment, the lentiviral vector encoding the immune receptor comprises the nucleic acid sequences of SEQ ID NO: 61 and SEQ ID NO: 62, the nucleic acid sequence of SEQ ID NO: 61 is located 5' to the sequence encoding the immune receptor, the nucleic acid sequence of SEQ ID NO: 62 is located 3' to the sequence encoding the immune receptor, and the vector is circularized. In one embodiment, the viral vector is an episomal vector. In one embodiment, the viral vector is an adenoviral vector. In one embodiment, the viral vector is an adeno-associated viral vector. In one embodiment, the nucleic acid comprises a nucleic acid sequence that enables stable integration into the genome of the host cell by transfer such as an inverted repeat. In an exemplary embodiment, the nucleic acid is a vector encoding an immune receptor comprising the nucleic acid sequences of SEQ ID NO: 63 and SEQ ID NO: 64, the nucleic acid sequence of SEQ ID NO: 63 is located 5' to the sequence encoding the immune receptor, the nucleic acid sequence of SEQ ID NO: 64 is located 3' to the sequence encoding the immune receptor, and the vector is circularized.

[0089] In a preferred embodiment, the nucleic acid may be integrated into the genome of the host cell by a site-specific genome modification method such as CRISPR / Cas9, zinc finger nuclease or TALEN. In one embodiment, the nucleic acid is DNA. In one embodiment, the nucleic acid is RNA. In one embodiment, the nucleic acid contains unnatural nucleotides. In one embodiment, the nucleic acid does not contain unnatural nucleotides.

[0090] The present invention provides a cell comprising a nucleic acid encoding an immune receptor according to the present invention. In a preferred embodiment, the cell expresses the immune receptor. In one embodiment, the cell may be induced to express the immune receptor. In a preferred embodiment, the cell is an immune cell. In a more preferred embodiment, the cell is a T cell. In a preferred embodiment, the T cell is a CD4+ T cell. In a preferred embodiment, the T cell is a CD8+ T cell. In a preferred embodiment, the T cell is a cytotoxic T cell (CTL). In one embodiment, the cell comprises all or part of a nucleic acid encoding an immune receptor according to the present invention stably integrated into its genome. In a preferred embodiment, the cell comprises the entire sequence encoding the immune receptor of the present invention stably integrated into its genome. In one embodiment, the cell comprises all or part of a nucleic acid encoding an immune receptor according to the present invention as an episome. In a preferred embodiment, the cell comprises the entire sequence stably encoding the immune receptor of the present invention as an episome.

[0091] In a preferred embodiment, the nucleic acid and cell comprising an immune receptor according to the present invention are provided for use in the treatment of cancer or autoimmune diseases, infectious diseases or degenerative diseases.

[0092] In a preferred embodiment, the cancer is a blood cancer. In a preferred embodiment, the blood cancer is leukemia or lymphoma, preferably acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, Burkitt lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, or diffuse large B-cell lymphoma. In one embodiment, the cancer is a solid cancer. In one embodiment, the solid cancer is breast cancer, colon cancer, lung cancer, or prostate cancer.

[0093] The present invention provides an antigen-binding protein that can specifically bind to an epitope consisting of an array of at least one, preferably at least two, more preferably at least three repeats of an IgG3 central hinge repeat domain motif. In a preferred embodiment, the antigen-binding protein according to the present invention can specifically bind to an epitope consisting of the junction of two adjacent IgG3 central hinge repeat domain motifs. In a preferred embodiment, the antigen-binding protein is an antibody or a fragment thereof.

[0094] In a preferred embodiment, the antigen-binding protein is an antibody or a fragment thereof, and includes, as complementarity-determining regions (CDRs) contained in the heavy-chain variable region, CDR1 having the amino acid sequence of SEQ ID NO: 20, CDR2 having the amino acid sequence of SEQ ID NO: 21, and CDR3 having the amino acid sequence of SEQ ID NO: 22, and, as complementarity-determining regions (CDRs) contained in the light-chain variable region, CDR1 having the amino acid sequence of SEQ ID NO: 24, CDR2 having the amino acid sequence of SEQ ID NO: 25, and CDR3 having the amino acid sequence of SEQ ID NO: 26.

[0095] In a preferred embodiment, the antigen-binding protein is an antibody or a fragment thereof, and includes a heavy-chain variable domain having at least 80%, preferably at least 90%, optionally 100% sequence identity with the amino acid sequence of SEQ ID NO: 19, and a light-chain variable region having at least 80%, preferably at least 90%, optionally 100% sequence identity with the amino acid sequence of SEQ ID NO: 23, and can specifically bind to one or more, preferably two or more, more preferably three or more IgG3 central hinge domain repeat motifs. In a preferred embodiment, the antibody or a fragment thereof maintains 100% sequence identity in its CDRs to SEQ ID NOs: 20, 21, 22, 24, 25, and 26.

[0096] In one embodiment, an antigen-binding protein capable of binding to an epitope consisting of at least one, preferably at least two, more preferably at least three IgG3 central hinge repeat domain motifs is an antigen-binding protein that does not contain SEQ ID NO: 19 and / or SEQ ID NO: 23.

[0097] The antigen-binding protein according to the present invention can be used for the purification, detection, depletion, stimulation, expansion, or concentration of cells expressing the immunoreceptor of the present invention.

[0098] The present invention provides a method comprising the step of binding the antigen-binding protein of the present invention to cells expressing the immunoreceptor according to the present invention.

[0099] In one embodiment, the method of the present invention is used for the purification of cells expressing the immunoreceptor of the present invention. In this embodiment, the cells are incubated with a primary antibody, which is an antigen-binding protein according to the present invention, under conditions that allow the primary antibody to bind to the immunoreceptor expressed on the surface of the cells, and then the cells are purified by separating the antibody-bound cells from the non-antibody-bound cells. In one embodiment, the incubation further comprises the step of incubating the cells with an entity capable of binding to the antibody. In a preferred embodiment, the entity is a fluorescent marker; or a secondary antibody preferably labeled with beads, preferably magnetic beads. In one embodiment, the primary antibody is preferably labeled with a tag or a fluorescent dye. In a preferred embodiment, the separation is carried out by means of MACS or FACS.

[0100] In one embodiment, the method of the present invention is used for the depletion of cells expressing the immunoreceptor of the present invention. In this embodiment, the cells are incubated with the antigen-binding protein according to the present invention conjugated to a cytotoxic molecule. In one embodiment, the antigen-binding protein is included in a chimeric antigen receptor expressed by another cell, preferably a T cell.

[0101] In one embodiment, the method of the present invention is used for the stimulation of cells expressing the immune receptor of the present invention. In this embodiment, the cells are incubated with the antigen-binding protein according to the present invention, thereby stimulating the cells. In a preferred embodiment, the antigen-binding protein is bound to a solid phase. In a preferred embodiment, the solid phase is a tissue culture surface. In a preferred embodiment, the solid phase is beads, preferably magnetic beads. In one embodiment, the antigen-binding protein is expressed on the surface of another cell.

[0102] In one embodiment, the method of the present invention is used for the expansion of cells expressing the immune receptor of the present invention. In this embodiment, the cells are incubated with the antigen-binding protein according to the present invention, thereby increasing proliferation and thus expanding the cells. In a preferred embodiment, the antigen-binding protein is bound to a solid phase. In a preferred embodiment, the solid phase is a tissue culture surface. In a preferred embodiment, the solid phase is beads, preferably magnetic beads. In one embodiment, the antigen-binding protein is expressed on the surface of another cell.

[0103] The present invention provides a method for concentrating cells expressing the immune receptor according to the present invention, the method comprising the steps of stimulating or expanding the cells using the stimulation method of the present invention, and then purifying the cells using the purification method of the present invention.

[0104] In one embodiment, the method or use of the present invention is an in vitro use or method. In one embodiment, the method or use of the present invention is an in vivo use or method. In one embodiment, the method or use of the present invention does not include a method for treating the body of a human or animal by surgery or therapy, or a diagnostic method performed on the body of a human or animal.

[0105] The present invention provides a pharmaceutical composition comprising the antigen-binding protein of the present invention.

[0106] The present invention provides a pharmaceutical composition comprising the nucleic acid of the present invention.

[0107] The present invention provides a pharmaceutical composition comprising cells expressing an immune receptor of the present invention.

[0108] The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier and / or excipient. The pharmaceutical composition may further comprise an additional active ingredient. In a preferred embodiment, the pharmaceutical composition is useful for treatment.

[0109] The present invention provides an antigen-binding protein or a pharmaceutical composition comprising the antigen-binding protein according to the present invention for use in a method of treating depletion of cells expressing an immune receptor of the present invention. In the method, cells expressing an antigen-binding protein bound to a cytotoxic molecule, optionally comprised in the pharmaceutical composition, or cells expressing the antigen-binding protein as part of a chimeric antigen receptor, are administered to a patient to whom the cells have been administered in order to deplete the cells expressing an immune receptor of the present invention.

[0110] The present invention provides a kit comprising an immune receptor of the present invention and an antigen-binding protein of the present invention. The present invention provides a kit comprising cells comprising nucleic acids encoding an immune receptor of the present invention and an antigen-binding protein of the present invention.

[0111] Sequence SEQ ID NO: 1 (15aa MiH repeat sequence) Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro

[0112] SEQ ID NO: 2 (upper hinge) Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro

[0113] SEQ ID NO: 3 (scFv CD19_FMC63 VH_linker_VL) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser

[0114] Sequence number 27 (scFv CD19_FMC63 VH) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr

[0115] Accession number 28 (scFv CD19_FMC63 VL) Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser

[0116] Accession number 4 (scFv CD20_Leu16 VL - linker - VH) Asp Ile Val Leu Thr Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Asn Tyr Met Asp Trp Tyr Gln Lys Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Phe Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp Val Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Tyr Cys Ala Arg Ser Asn Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser

[0117] Sequence number 29 (scFv CD20_Leu16 VL) Asp Ile Val Leu Thr Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Asn Tyr Met Asp Trp Tyr Gln Lys Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Phe Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0118] Sequence number 30 (scFv CD20_Leu16 VH) Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp Val Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Tyr Cys Ala Arg Ser Asn Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser

[0119] Sequence number 5 (scFv ROR1_2A2 VH_4GS3_VL) Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp Tyr Glu Met His Trp Val Ile Gln Thr Pro Val His Gly Leu Glu Trp Ile Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys Gly Lys Ala Ile Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Thr Gly Tyr Tyr Asp Tyr Asp Ser Phe Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Gln Lys Ile Met Ser Thr Thr Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ala Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Met Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Asp Ile Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0120] Sequence number 31 (scFv ROR1_2A2 VH) Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp Tyr Glu Met His Trp Val Ile Gln Thr Pro Val His Gly Leu Glu Trp Ile Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys Gly Lys Ala Ile Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Thr Gly Tyr Tyr Asp Tyr Asp Ser Phe Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala

[0121] Sequence number 32 (scFv ROR1_2A2 VL) Asp Ile Val Met Thr Gln Ser Gln Lys Ile Met Ser Thr Thr Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ala Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Met Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Asp Ile Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0122] Sequence number 6 (scFv ROR1_4-2 VH_4GS3_VL) Gln Glu Gln Gln Lys Glu Ser Gly Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Asp Ile Ser Ser Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Trp Ile Gly Ala Ile Gly Ile Ser Gly Asn Ala Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp His Pro Thr Tyr Gly Met Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Tyr Glu Leu Thr Gln Leu Pro Ser Val Ser Val Ser Leu Gly Gln Thr Ala Arg Ile Thr Cys Glu Gly Asn Asn Ile Gly Ser Lys Ala Val His Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Gly Leu Leu Ile Tyr Asp Asp Asp Glu Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Asn Ser Gly Asp Thr Ala Thr Leu Thr Ile Ser Gly Ala Gln Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Ala Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0123] SEQ ID NO: 33 (scFv ROR1_4-2 VH) Gln Glu Gln Gln Lys Glu Ser Gly Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Asp Ile Ser Ser Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Trp Ile Gly Ala Ile Gly Ile Ser Gly Asn Ala Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp His Pro Thr Tyr Gly Met Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser

[0124] Sequence number 34 (scFv ROR1_4-2 VL) Ser Tyr Glu Leu Thr Gln Leu Pro Ser Val Ser Val Ser Leu Gly Gln Thr Ala Arg Ile Thr Cys Glu Gly Asn Asn Ile Gly Ser Lys Ala Val His Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Gly Leu Leu Ile Tyr Asp Asp Asp Glu Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Asn Ser Gly Asp Thr Ala Thr Leu Thr Ile Ser Gly Ala Gln Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Ala Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0125] Accession number 7 (scFv ROR1_R11 VH_4GS3_VL) Gln Ser Val Lys Glu Ser Glu Gly Asp Leu Val Thr Pro Ala Gly Asn Leu Thr Leu Thr Cys Thr Ala Ser Gly Ser Asp Ile Asn Asp Tyr Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Phe Ile Asn Ser Gly Gly Ser Thr Trp Tyr Ala Ser Trp Val Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Met Thr Ser Leu Thr Thr Asp Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr Ser Thr Tyr Tyr Gly Asp Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Met Thr Gln Thr Pro Ser Ser Thr Ser Gly Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Ile Asp Ser Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Thr Leu Leu Ile Tyr Arg Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Gly Val Gly Asn Val Ser Tyr Arg Thr Ser Phe Gly Gly Gly Thr Glu Val Val Val Lys

[0126] Sequence number 35 (scFv ROR1_R11 VH) Gln Ser Val Lys Glu Ser Glu Gly Asp Leu Val Thr Pro Ala Gly Asn Leu Thr Leu Thr Cys Thr Ala Ser Gly Ser Asp Ile Asn Asp Tyr Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Phe Ile Asn Ser Gly Gly Ser Thr Trp Tyr Ala Ser Trp Val Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Met Thr Ser Leu Thr Thr Asp Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr Ser Thr Tyr Tyr Gly Asp Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser

[0127] Sequence number 36 (scFv ROR1_R11 VL) Glu Leu Val Met Thr Gln Thr Pro Ser Ser Thr Ser Gly Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Ile Asp Ser Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Thr Leu Leu Ile Tyr Arg Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Gly Val Gly Asn Val Ser Tyr Arg Thr Ser Phe Gly Gly Gly Thr Glu Val Val Val Lys

[0128] Sequence number 8 (scFv ROR1_R12 VH - linker - VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0129] Sequence number 37 (scFv ROR1_R12 VH) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser

[0130] Sequence number 38 (scFv ROR1_R12 VL) Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0131] Sequence number 9 (scFv ROR2_4-1 VH_4GS3_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0132] Sequence number 39 (scFv ROR2_4-1 VH) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser

[0133] Sequence number 40 (scFv ROR2_4-1 VL) Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0134] Accession number 10 (scFv SLAMF7_ERCS409 VH_4GS3_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Ser Tyr Gly Val Ile Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile Gly Ile Ile Gly Ser Ser Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Arg Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Tyr Tyr Gly Asp Ser Gly Phe Asp Ser Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Gln Val Leu Thr Gln Thr Pro Ser Ser Thr Ser Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Gly Ser Trp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Gly Arg Ser Gly Thr Glu Tyr Ser Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ala Ser Pro Asn Gly Trp Ala Phe Gly Ala Gly Thr Asn Val Glu Ile Lys

[0135] Sequence number 41 (scFv SLAMF7_ERCS409 VH) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Ser Tyr Gly Val Ile Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile Gly Ile Ile Gly Ser Ser Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Arg Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Tyr Tyr Gly Asp Ser Gly Phe Asp Ser Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser

[0136] Sequence number 42 (scFv SLAMF7_ERCS409 VL) Ala Gln Val Leu Thr Gln Thr Pro Ser Ser Thr Ser Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Gly Ser Trp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Gly Arg Ser Gly Thr Glu Tyr Ser Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ala Ser Pro Asn Gly Trp Ala Phe Gly Ala Gly Thr Asn Val Glu Ile Lys

[0137] Sequence number 11 (scFv SLAMF7_huLuc63 VH_4GS3_VL) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

[0138] Accession number 43 (scFv SLAMF7_huLuc63 VH) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

[0139] Accession number 44 (scFv SLAMF7_huLuc63 VL) Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

[0140] Sequence number 12 (scFv FLT3_BV10 VH_4GS3_VL) Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr Gly Leu His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ala Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Lys Gly Gly Ile Tyr Tyr Ala Asn His Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Met Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn Asp His Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg

[0141] Sequence number 45 (scFv FLT3_BV10 VH) Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr Gly Leu His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ala Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Lys Gly Gly Ile Tyr Tyr Ala Asn His Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser

[0142] Sequence number 46 (scFv FLT3_BV10 VL) Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Met Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn Asp His Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg

[0143] Sequence number 13 (scFv FLT3_4G8 VH_4GS3_VL) Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Leu Lys Leu Ser Cys Lys Ser Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Glu Ile Asp Pro Ser Asp Ser Tyr Lys Asp Tyr Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Asn Thr Ala Tyr Met His Leu Ser Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys Ala Arg Ala Ile Thr Thr Thr Pro Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro Gly Asp Ser Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Asn Asn Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Thr Glu Asp Phe Gly Val Tyr Phe Cys Gln Gln Ser Asn Thr Trp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg

[0144] Accession number 47 (scFv FLT3_4G8 VH) Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Leu Lys Leu Ser Cys Lys Ser Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Glu Ile Asp Pro Ser Asp Ser Tyr Lys Asp Tyr Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Asn Thr Ala Tyr Met His Leu Ser Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys Ala Arg Ala Ile Thr Thr Thr Pro Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser

[0145] Accession number 48 (scFv FLT3_4G8 VL) Asp Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro Gly Asp Ser Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Asn Asn Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Thr Glu Asp Phe Gly Val Tyr Phe Cys Gln Gln Ser Asn Thr Trp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg

[0146] Sequence number 14 (scFv Siglec-6_JML-1 VH_4GS3_VL) Lys Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Gly Gln Thr Ile Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

[0147] Sequence number 49 (scFv Siglec-6_JML-1 VH) Lys Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Gly Gln Thr Ile Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

[0148] Sequence number 50 (scFv Siglec-6_JML-1 VL) Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

[0149] Accession number 15 (scFv avb3_LM609v7 VH_4GS3_VL) Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser Ile Ser Arg Gly Gly Tyr Tyr Trp Ser Trp Ile Arg Gln Tyr Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile His His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ala Ile Asp Thr Ser Lys Asn Gln Leu Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Asn Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0150] SEQ ID NO: 51 (scFv avb3_LM609v7 VH) Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser Ile Ser Arg Gly Gly Tyr Tyr Trp Ser Trp Ile Arg Gln Tyr Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile His His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ala Ile Asp Thr Ser Lys Asn Gln Leu Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

[0151] Accession number 52 (scFv avb3_LM609v7 VL) Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Asn Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0152] Accession number 16 (scFv avb3_LM609v11 VH_4GS3_VL) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser Ser Val Arg Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Gly Phe Ala Val Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Phe Glu Trp Leu Gly Gly Ile Val Ala Ser Leu Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln Asp Lys Leu Thr Ile Thr Val Asp Glu Ser Thr Ala Thr Val Tyr Met Glu Met Arg Asn Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Thr Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Tyr Ser Leu Glu Ala Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0153] Accession number 53 (scFv avb3_LM609v11 VH) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser Ser Val Arg Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Gly Phe Ala Val Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Phe Glu Trp Leu Gly Gly Ile Val Ala Ser Leu Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln Asp Lys Leu Thr Ile Thr Val Asp Glu Ser Thr Ala Thr Val Tyr Met Glu Met Arg Asn Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

[0154] Accession number 54 (scFv avb3_LM609v11 VL) Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Thr Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Tyr Ser Leu Glu Ala Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0155] Sequence number 17 (scFv BCMA_BCMA30 VH_4GS3_VL) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Ala Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Glu Thr Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0156] Sequence number 55 (scFv BCMA_BCMA30 VH) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

[0157] Sequence number 56 (scFv BCMA_BCMA30 VL) Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Ala Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Glu Thr Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0158] Sequence number 18 (scFv BCMA_BCMA50 VH_4GS3_VL) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Ile Tyr Tyr Cys Ser Gln Ser Ser Ile Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0159] Sequence number 57 (scFv BCMA_BCMA50 VH) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

[0160] Sequence number 58 (scFv BCMA_BCMA50 VL) Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Ile Tyr Tyr Cys Ser Gln Ser Ser Ile Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0161] Sequence number 19 (anti MiH repeat heavy chain variable region) Gln Val Gln Leu Leu Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Phe Thr Asn Tyr Asp Leu His Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ala Val Gly Ser Thr Asn Tyr Asn Ser Ala Leu Met Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Glu Glu Asp Tyr Arg Tyr Gly Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser

[0162] Sequence number 20 (anti-MiH repeat heavy chain CDR1) Gly Phe Ser Phe Thr Asn Tyr

[0163] Sequence number 21 (anti-MiH repeat heavy chain CDR2) Trp Ala Val Gly Ser

[0164] Sequence number 22 (anti-MiH repeat heavy chain CDR3) Glu Glu Asp Tyr Arg Tyr Gly Met Asp Tyr

[0165] Sequence number 23 (anti-MiH repeat light chain variable region) Glu Leu Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0166] Sequence number 24 (anti-MiH repeat light chain CDR1) Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His

[0167] Sequence number 25 (anti MiH repeat light chain CDR2) Lys Val Ser Asn Arg Phe Ser

[0168] Sequence number 26 (anti MiH repeat light chain CDR3) Ser Gln Ser Thr His Val Pro Tyr Thr

[0169] Sequence number 59 (CPRCP) CPRCP

[0170] Sequence number 60 (IgG3 lower hinge) APELLGGP

[0171] Sequence number 61 (lentiviral vector backbone 5')

[0172] Array number 62 (Lentiviral vector backbone 3')

[0173] Array number 63 (Sleeping Beauty vector backbone 5')

[0174] SEQ ID NO: 64 (Sleeping Beauty vector backbone 3')

[0175] Sequence number 65 (CAR transmembrane domain) Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val

[0176] Sequence number 66 (CAR 4-1BB domain) Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

[0177] Sequence number 67 (CAR CD3 zeta domain) Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0178] Array number 68 (CD19 CAR) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0179] Sequence number 69 (CD19 CAR SB vector, with the CAR insert underlined)

[0180]

Chem.

[0181]

Chem.

[0182] Sequence number 70 (CD19 CAR LV vector, with the inserted CAR underlined)

[0183]

Chem.

[0184]

Chem.

[0185] [Chem.]

[0186] Accession No. 71 (scFv CD19_FMC63 VH_MiH5_VL) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser

[0187] Sequence number 72 (scFv CD20_Leu16 VL_MiH5_VH) Asp Ile Val Leu Thr Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Asn Tyr Met Asp Trp Tyr Gln Lys Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Phe Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp Val Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Tyr Cys Ala Arg Ser Asn Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser

[0188] Sequence number 73 (scFv ROR1_2A2 VH_MiH5_VL) Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp Tyr Glu Met His Trp Val Ile Gln Thr Pro Val His Gly Leu Glu Trp Ile Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys Gly Lys Ala Ile Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Thr Gly Tyr Tyr Asp Tyr Asp Ser Phe Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Ser Gln Lys Ile Met Ser Thr Thr Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ala Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Met Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Asp Ile Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0189] Sequence number 74 (scFv ROR1_4-2 VH_MiH5_VL) Gln Glu Gln Gln Lys Glu Ser Gly Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Asp Ile Ser Ser Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Trp Ile Gly Ala Ile Gly Ile Ser Gly Asn Ala Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp His Pro Thr Tyr Gly Met Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ser Tyr Glu Leu Thr Gln Leu Pro Ser Val Ser Val Ser Leu Gly Gln Thr Ala Arg Ile Thr Cys Glu Gly Asn Asn Ile Gly Ser Lys Ala Val His Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Gly Leu Leu Ile Tyr Asp Asp Asp Glu Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Asn Ser Gly Asp Thr Ala Thr Leu Thr Ile Ser Gly Ala Gln Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Ala Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0190] Sequence number 75 (scFv ROR1_R11 VH_MiH5_VL) Gln Ser Val Lys Glu Ser Glu Gly Asp Leu Val Thr Pro Ala Gly Asn Leu Thr Leu Thr Cys Thr Ala Ser Gly Ser Asp Ile Asn Asp Tyr Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Phe Ile Asn Ser Gly Gly Ser Thr Trp Tyr Ala Ser Trp Val Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Met Thr Ser Leu Thr Thr Asp Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr Ser Thr Tyr Tyr Gly Asp Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Met Thr Gln Thr Pro Ser Ser Thr Ser Gly Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Ile Asp Ser Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Thr Leu Leu Ile Tyr Arg Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Gly Val Gly Asn Val Ser Tyr Arg Thr Ser Phe Gly Gly Gly Thr Glu Val Val Val Lys

[0191] SEQ ID NO: 76 (scFv ROR1_R12 VH_MiH5_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0192] Sequence number 77 (scFv ROR2_4-1 VH_MiH5_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0193] Sequence number 78 (scFv SLAMF7_ERCS409 VH_MiH5_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Ser Tyr Gly Val Ile Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile Gly Ile Ile Gly Ser Ser Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Arg Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Tyr Tyr Gly Asp Ser Gly Phe Asp Ser Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala Gln Val Leu Thr Gln Thr Pro Ser Ser Thr Ser Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Gly Ser Trp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Gly Arg Ser Gly Thr Glu Tyr Ser Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ala Ser Pro Asn Gly Trp Ala Phe Gly Ala Gly Thr Asn Val Glu Ile Lys

[0194] Sequence number 79 (scFv SLAMF7_huLuc63 VH_MiH5_VL) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

[0195] Sequence number 80 (scFv FLT3_BV10 VH_MiH5_VL) Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr Gly Leu His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ala Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Lys Gly Gly Ile Tyr Tyr Ala Asn His Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Met Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn Asp His Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg

[0196] Sequence number 81 (scFv FLT3_4G8 VH_MiH5_VL) Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Leu Lys Leu Ser Cys Lys Ser Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Glu Ile Asp Pro Ser Asp Ser Tyr Lys Asp Tyr Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Asn Thr Ala Tyr Met His Leu Ser Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys Ala Arg Ala Ile Thr Thr Thr Pro Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro Gly Asp Ser Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Asn Asn Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Thr Glu Asp Phe Gly Val Tyr Phe Cys Gln Gln Ser Asn Thr Trp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg

[0197] Sequence number 82 (scFv Siglec-6_JML-1 VH_MiH5_VL) Lys Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Gly Gln Thr Ile Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

[0198] Sequence number 83 (scFv avb3_LM609v7 VH_MiH5_VL) Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser Ile Ser Arg Gly Gly Tyr Tyr Trp Ser Trp Ile Arg Gln Tyr Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile His His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ala Ile Asp Thr Ser Lys Asn Gln Leu Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Asn Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0199] Sequence number 84 (scFv avb3_LM609v11 VH_MiH5_VL) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser Ser Val Arg Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Gly Phe Ala Val Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Phe Glu Trp Leu Gly Gly Ile Val Ala Ser Leu Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln Asp Lys Leu Thr Ile Thr Val Asp Glu Ser Thr Ala Thr Val Tyr Met Glu Met Arg Asn Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Thr Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Tyr Ser Leu Glu Ala Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0200] Sequence number 85 (scFv BCMA_BCMA30 VH_MiH5_VL) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Ala Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Glu Thr Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0201] Sequence number 86 (scFv BCMA_BCMA50 VH_MiH5_VL) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Ile Tyr Tyr Cys Ser Gln Ser Ser Ile Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

[0202] Sequence number 87 (scFv ROR1_ huR12 VH_linker_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0203] Sequence number 88 (scFv ROR1_ huR12 VH_MiH5_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0204] Sequence number 89 (scFv ROR1_R12 / V16 VH_linker_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0205] Sequence number 90 (scFv ROR1_R12 / V16 VH_MiH5_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0206] Sequence number 91 (scFv ROR1_R12 / V20 VH_linker_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0207] Sequence number 92 (scFv ROR1_R12 / V20 VH_MiH5_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0208] Sequence number 93 (scFv ROR1_R12 / V16-20 VH_linker_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0209] Sequence number 94 (scFv ROR1_R12 / V16-20 VH_MiH5_VL) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly

[0210] Sequence number 95 (scFv ROR1_ huR12 / V16 VH_linker_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0211] Sequence number 96 (scFv ROR1_ huR12 / V16 VH_MiH5_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln AlaAsp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0212] Sequence number 97 (scFv ROR1_ huR12 / V20 VH_linker_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0213] SEQ ID NO: 98 (scFv ROR1_ huR12 / V20 VH_MiH5_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0214] Sequence number 99 (scFv ROR1_ huR12 / V16-20 VH_linker_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0215] Sequence number 100 (scFv ROR1_ huR12 / V16-20 VH_MiH5_VL) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly

[0216] Sequence number 101 (scFv ROR2_X3.12 VH_4GS3_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0217] Sequence number 102 (scFv ROR2_X3.12 VH_MiH5_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0218] Sequence number 103 (scFv ROR2_XBR2-401-DM VH_4GS3_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Gly Arg Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0219] Sequence number 104 (scFv ROR2_XBR2-401-DM VH_MiH5_VL) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Gly Arg Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0220] SEQ ID NO: 105 (scFv ROR2_huX3.12.5 VH_4GS3_VL) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Pro Met Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0221] Sequence number 106 (scFv ROR2_huX3.12.5 VH_MiH5_VL) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0222] Sequence number 107 (scFv ROR2_huX3.12.6 VH_4GS3_VL) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Pro Met Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0223] Sequence number 108 (scFv ROR2_huX3.12.6 VH_MiH5_VL) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

[0224] SEQ ID NO: 109 (CD28tm+CD28 / zeta) Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg Gly Gly His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0225] Accession No. 110 (CD28tm+4-1BB / zeta) Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0226] Sequence number 111 (CD28tm + CD28 / 4-1BB / zeta) Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg Gly Gly His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0227] Sequence number 112 (CD28tm+4-1BB / CD28 / zeta) Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Ser Lys Arg Ser Arg Gly Gly His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0228] SEQ ID NO: 113 (CD28tm + zeta) Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0229] Sequence number 114 (ICOStm+zeta) Phe Trp Leu Pro Ile Gly Cys Ala Ala Phe Val Val Val Cys Ile Leu Gly Cys Ile Leu Ile Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0230] Sequence number 115 (OX40tm+OX40 / zeta) Val Ala Ala Ile Leu Gly Leu Gly Leu Val Leu Gly Leu Leu Gly Pro Leu Ala Ile Leu Leu Ala Leu Tyr Leu Leu Arg Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys Pro Pro Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala Asp Ala His Ser Thr Leu Ala Lys Ile Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0231] SEQ ID NO: 174 (intracellular CD4tm+) Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe Phe Cys Val Arg Cys Arg His Arg Arg Arg Gln Ala Glu Arg Met Ser Gln Ile Lys Arg Leu Leu Ser Glu Lys Lys Thr Cys Gln Cys Pro His Arg Phe Gln Lys Thr Cys Ser Pro Ile

[0232] SEQ ID NO: 116 (scFv CD19_FMC63 VH_MiH5_VL_MiH0_ CD28tm+4-1BB / zeta) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0233] Sequence number 117 (scFv CD19_FMC63 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0234] SEQ ID NO: 118 (scFv CD20_Leu16 VL_MiH5_VH_MiH3_ CD28tm+4-1BB / zeta) Asp Ile Val Leu Thr Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Asn Tyr Met Asp Trp Tyr Gln Lys Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Phe Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp Val Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Tyr Cys Ala Arg Ser Asn Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0235] Sequence number 119 (scFv ROR1_2A2 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp Tyr Glu Met His Trp Val Ile Gln Thr Pro Val His Gly Leu Glu Trp Ile Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys Gly Lys Ala Ile Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Thr Gly Tyr Tyr Asp Tyr Asp Ser Phe Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Ser Gln Lys Ile Met Ser Thr Thr Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ala Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Met Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Asp Ile Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0236] Sequence number 120 (scFv ROR1_4-2 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Glu Gln Gln Lys Glu Ser Gly Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Asp Ile Ser Ser Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Trp Ile Gly Ala Ile Gly Ile Ser Gly Asn Ala Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp His Pro Thr Tyr Gly Met Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ser Tyr Glu Leu Thr Gln Leu Pro Ser Val Ser Val Ser Leu Gly Gln Thr Ala Arg Ile Thr Cys Glu Gly Asn Asn Ile Gly Ser Lys Ala Val His Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Gly Leu Leu Ile Tyr Asp Asp Asp Glu Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Asn Ser Gly Asp Thr Ala Thr Leu Thr Ile Ser Gly Ala Gln Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Ala Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0237] Sequence number 121 (scFv ROR1_R11 VH_MiH5_VL_MiH3_ CD28tm+4-1BB / zeta) Gln Ser Val Lys Glu Ser Glu Gly Asp Leu Val Thr Pro Ala Gly Asn Leu Thr Leu Thr Cys Thr Ala Ser Gly Ser Asp Ile Asn Asp Tyr Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Phe Ile Asn Ser Gly Gly Ser Thr Trp Tyr Ala Ser Trp Val Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Met Thr Ser Leu Thr Thr Asp Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr Ser Thr Tyr Tyr Gly Asp Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Met Thr Gln Thr Pro Ser Ser Thr Ser Gly Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Ile Asp Ser Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Thr Leu Leu Ile Tyr Arg Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Gly Val Gly Asn Val Ser Tyr Arg Thr Ser Phe Gly Gly Gly Thr Glu Val Val Val Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0238] Sequence number 122 (scFv ROR1_R12 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0239] Sequence number 123 (scFv ROR1_huR12 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0240] Sequence number 124 (scFv ROR1_R12 / V16 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0241] Sequence number 125 (scFv ROR1_R12 / V20 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0242] Sequence number 126 (scFv ROR1_R12 / V16-20 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Glu Gln Leu Val Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Ser Asp Asn Ala Gln Asn Thr Val Asp Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Arg Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Ile Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Pro Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Gln Gly Glu Ala Pro Arg Tyr Leu Met Gln Val Gln Ser Asp Gly Ser Tyr Thr Lys Arg Pro Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Pro Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Thr Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0243] SEQ ID NO: 127 (scFv ROR1_huR12 / V16 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0244] Sequence number 128 (scFv ROR1_huR12 / V20 VH_MiH5_VL_MiH1_ CD28tm + 4-1BB / zeta) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr Ile Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0245] Sequence number 129 (scFv ROR1_huR12 / V16-20 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val Gln Gly Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Ser Tyr Gly Glu Asp Leu Gly Leu Phe Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Glu Ser Arg Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0246] Accession No. 130 (scFv ROR2_4-2 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0247] Sequence number 131 (scFv ROR2_X3.12 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0248] Sequence number 132 (scFv ROR2_XBR2-40,1-DM VH_MiH5_VL_MiH1_CD28tm+4-1BB / zeta) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Ser Gly Leu Glu Trp Ile Gly Tyr Ile Asn Gly Arg Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Asn Glu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Trp Thr Ser Leu Asn Ile Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Thr Pro Ser Ser Thr Ser Thr Ala Val Gly Asp Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Ile Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0249] Sequence number 133 (scFv ROR2_huX3.12.5 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0250] Sequence number 134 (scFv ROR2_huX3.12.6 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Asn Thr Ala Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asp Arg Trp Ser Leu Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Pro Met Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser Asp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Tyr Gly Thr Glu Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Ala Asp Ala Ser Tyr Arg Thr Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0251] Sequence number 135 (scFv SLAMF7_ERCS409 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Ser Val Lys Glu Ser Glu Gly Gly Leu Phe Lys Pro Thr Asp Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Ser Tyr Gly Val Ile Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile Gly Ile Ile Gly Ser Ser Gly Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Ser Arg Ser Thr Ile Thr Arg Asn Thr Arg Leu Asn Thr Val Thr Leu Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Tyr Tyr Gly Asp Ser Gly Phe Asp Ser Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala Gln Val Leu Thr Gln Thr Pro Ser Ser Thr Ser Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Gly Ser Trp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Gly Arg Ser Gly Thr Glu Tyr Ser Leu Thr Ile Ser Gly Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ala Ser Pro Asn Gly Trp Ala Phe Gly Ala Gly Thr Asn Val Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0252] SEQ ID NO: 136 (scFv SLAMF7_huLuc63 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0253] Sequence number 137 (scFv FLT3_BV10 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr Gly Leu His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ala Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Lys Gly Gly Ile Tyr Tyr Ala Asn His Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Met Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn Asp His Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0254] SEQ ID NO: 138 (scFv FLT3_4G8 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Leu Lys Leu Ser Cys Lys Ser Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Glu Ile Asp Pro Ser Asp Ser Tyr Lys Asp Tyr Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Asn Thr Ala Tyr Met His Leu Ser Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys Ala Arg Ala Ile Thr Thr Thr Pro Phe Asp Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro Gly Asp Ser Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Asn Asn Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Thr Glu Asp Phe Gly Val Tyr Phe Cys Gln Gln Ser Asn Thr Trp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0255] Sequence number 139 (scFv Siglec-6_JML-1 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Lys Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Gly Gln Thr Ile Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0256] Accession number 140 (scFv avb3_LM609v7 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser Ile Ser Arg Gly Gly Tyr Tyr Trp Ser Trp Ile Arg Gln Tyr Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile His His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ala Ile Asp Thr Ser Lys Asn Gln Leu Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Asn Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0257] SEQ ID NO: 141 (scFv avb3_LM609v11 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser Ser Val Arg Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Gly Phe Ala Val Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Phe Glu Trp Leu Gly Gly Ile Val Ala Ser Leu Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln Asp Lys Leu Thr Ile Thr Val Asp Glu Ser Thr Ala Thr Val Tyr Met Glu Met Arg Asn Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Asn Tyr Gly Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Leu Val Met Thr Gln Ser Pro Glu Phe Gln Ser Val Thr Pro Lys Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Thr Ser Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Lys Tyr Ala Ser Gln Pro Val Phe Gly Val Pro Ser Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Tyr Ser Leu Glu Ala Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro His Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0258] Sequence number 142 (scFv BCMA_BCMA30 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Ala Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Glu Thr Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0259] SEQ ID NO: 143 (scFv BCMA_BCMA50 VH_MiH5_VL_MiH1_ CD28tm+4-1BB / zeta) Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Pro Asp Tyr Tyr Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Tyr Phe Ala Ser Gly Asn Ser Glu Tyr Asn Gln Lys Phe Thr Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Ser Leu Tyr Asp Tyr Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Ile Tyr Tyr Cys Ser Gln Ser Ser Ile Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

[0260] Sequence number 144 (scFv CD19_FMC63 VH_linker_VL_MiH0_CD28tm+4-1BB / zeta) Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu L...

Claims

1. An immunoreceptor comprising one or more IgG3 central hinge repeat domain motifs, said immunoreceptor not comprising an IgG3 CH2 and / or CH3 domain.

2. [A-B n ​ (wherein A is the amino acid sequence of SEQ ID NO: 2, B is said IgG3 central hinge domain repeat motif, said motif having the amino acid sequence of SEQ ID NO: 1, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5) The immunoreceptor according to claim 1, comprising an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, or most preferably 100% sequence identity to the amino acid sequence of.

3. [A-B n The immune receptor according to claim 2, comprising an amino acid sequence having 100% sequence identity with the amino acid sequence of

4. The immunoreceptor according to claim 2 or 3, wherein n is an integer between 1 and 10.

5. The immunoreceptor according to claim 2 or 3, wherein n is an integer between 1 and 5.

6. The immunoreceptor according to claim 2 or 3, wherein n is an integer between 3 and 5.

7. An extracellular antigen-binding domain, a spacer domain, a transmembrane domain, and an intracellular signaling domain comprising, wherein the spacer domain is located between the extracellular antigen-binding domain and the transmembrane domain, optionally the spacer domain comprises one or more IgG3 central hinge domain repeat motifs, the immunoreceptor according to any one of claims 1 to 6.

8. The immunoreceptor according to claim 7, wherein both the transmembrane domain and the intracellular domain consist of a sequence selected from the group consisting of SEQ ID NOs: 109, 110, 111, 112, 113, 114, 115 and 174.

9. A first domain, a linker, optionally, and a second domain comprising an extracellular antigen-binding domain, optionally the linker is located between the first domain and the second domain, optionally the linker comprises one or more IgG3 central hinge domain repeat motifs, the immunoreceptor according to any one of claims 1 to 8.

10. The spacer domain comprises one or more IgG3 central hinge domain repeat motifs, and / or The linker included in the extracellular antigen-binding domain comprises one or more IgG3 central hinge domain repeat motifs. The immunoreceptor according to claim 7, 8 or 9.

11. The immunoreceptor according to any one of claims 1 to 10, selected from the group consisting of a T cell receptor (TCR), preferably a recombinant TCR; a B cell receptor (BCR), preferably a recombinant BCR; and a chimeric antigen receptor (CAR).

12. The immunoreceptor comprises an antigen-binding domain. I) The first domain comprises a heavy chain variable domain. II) The first domain comprises a light chain variable domain. III) The first domain comprises a heavy chain variable domain and the second domain comprises a light chain variable domain. IV) The first domain comprises a heavy chain variable domain and the second domain comprises a heavy chain variable domain, or V) The first domain comprises a light chain variable domain and the second domain comprises a light chain variable domain. The immunoreceptor according to any one of claims 9 to 11.

13. The immunoreceptor comprises an antigen-binding domain, and the antigen-binding domain comprises a first domain that is part of a single-chain variable fragment (scFv), a linker, and a second domain. The scFv optionally comprises the heavy chain / light chain variable sequences of an scFv specific for one of the following antigens as the heavy chain / light chain variable sequences comprised in the first / second domain: A) CD19, optionally i) The heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO:

27. The light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO:

28. The scFv can specifically bind to CD19, or ii) The heavy chain variable domain has the amino acid sequence of SEQ ID NO: 27 and the light chain variable domain has the amino acid sequence of SEQ ID NO:

28. B) CD20, optionally i) The heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO:

30. The light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO:

29. The scFv can specifically bind to CD20, or ii) The heavy chain variable domain has the amino acid sequence of SEQ ID NO: 30, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 29; C) ROR1, optionally, i) respectively, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 31, 33, 35, or 37, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 32, 34, 36, or 38, and the scFv can specifically bind to ROR1, or ii) respectively, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 31, 33, 35, or 37, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 32, 34, 36, or 38; D) ROR2, optionally, i) the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 39, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 40, and the scFv can specifically bind to ROR2, or ii) the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 39, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 40; E) SLAMF7, optionally, i) respectively, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 41 or 43, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 42 or 44, and the scFv can specifically bind to SLAMF7, or ii) respectively, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 41 or 43, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 42 or 44; F) FLT3, optionally, i) respectively, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 45 or 47, The light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 46 or 48, the scFv can specifically bind to FLT3, or ii) respectively, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 45 or 47, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 46 or 48; G) Siglec-6, optionally, i) the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 49, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 50, the scFv can specifically bind to Siglec-6, or ii) the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 49, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 50; H) α v β 3 Integrin, optionally, i) respectively, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 51 or 53, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 52 or 54, The scFv can specifically bind to α v β 3 integrin, or ii) respectively, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 51 or 53, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 52 or 54; or I) BCMA, optionally, i) respectively, the heavy chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 55 or 57, the light chain variable domain has an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 56 or 58, the scFv can specifically bind to BCMA, or ii) respectively, the heavy chain variable domain has the amino acid sequence of SEQ ID NO: 55 or 57, and the light chain variable domain has the amino acid sequence of SEQ ID NO: 56 or 58, The immune receptor according to any one of claims 9 to 12.

14. The immune receptor comprises an antigen-binding domain, and the antigen-binding domain comprises the following scFv: I) An scFv specific for CD19, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 3 or 71, and can specifically bind to CD19, or said scFv has the amino acid sequence of SEQ ID NO: 3 or 71; II) An scFv specific for CD20, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 4 or 72, and can specifically bind to CD20, or said scFv has the amino acid sequence of SEQ ID NO: 4 or 72; III) An scFv specific for ROR1, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 5, 6, 7, 8, 73, 74, 75, 76, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100, and can specifically bind to ROR1, or said scFv has the amino acid sequence of SEQ ID NO: 5, 6, 7, 8, 73, 74, 75, 76, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100; IV) An scFv specific for ROR2, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 9, 77, 101, 102, 103, 104, 105, 106, 107 or 108, and can specifically bind to ROR2, or said scFv has the amino acid sequence of SEQ ID NO: 9, 77, 101, 102, 103, 104, 105, 106, 107 or 108; V) An scFv specific for SLAMF7, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 10, 11, 78 or 79, and can specifically bind to SLAMF7, or said scFv has the amino acid sequence of SEQ ID NO: 10, 11, 78 or 79; VI) An scFv specific for FLT3, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 12, 13, 80 or 81, and can specifically bind to FLT3, or said scFv has the amino acid sequence of SEQ ID NO: 12, 13, 80 or 81; VII) An scFv specific for Siglec-6, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 14 or 82, and can specifically bind to Siglec-6, or said scFv has the amino acid sequence of SEQ ID NO: 14 or 82; VIII) α v β 3 An scFv specific for integrin, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 15, 16, 83 or 84, α v β 3 Capable of specifically binding to integrin, or said scFv has the amino acid sequence of SEQ ID NO: 15, 16, 83 or 84; IX) An scFv specific for BCMA, optionally, said scFv comprises an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, to SEQ ID NO: 17, 18, 85 or 86, and can specifically bind to BCMA, or said scFv has the amino acid sequence of SEQ ID NO: 17, 18, 85 or 86, The immune receptor according to any one of claims 9 to 13.

15. The immune receptor according to any one of claims 1 to 14, which is a chimeric antigen receptor (CAR).

16. One or more IgG3 central hinge domain repeat motifs are I) derived from the human IgG3 central hinge, and / or II) consist of the amino acid sequence of SEQ ID NO: 1, and / or III) have reduced immunogenicity compared to repeats of the IgG1 hinge domain and / or IgG4 hinge domain, the immune receptor or CAR according to any one of claims 1 to 15.

17. I) does not contain all or part of the sequence of the lower hinge domain of the human IgG3 hinge domain, II) [A-B n ​ (wherein A is the amino acid sequence of SEQ ID NO: 2, B is the IgG3 central hinge domain repeat motif, and said motif has the amino acid sequence of SEQ ID NO: 1, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5) and the amino acid sequence of comprising an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, or most preferably 100% sequence identity, III) comprising 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 IgG3 central hinge domain repeat motifs, and / or IV) an immunoreceptor or CAR according to any one of claims 1 to 16, having reduced immunogenicity compared to a second CAR that differs from the first CAR in that it does not comprise said one or more IgG3 central hinge domain repeat motifs.

18. An immunoreceptor or CAR according to any one of claims 1 to 17, comprising at least two, preferably at least three, of said IgG3 central hinge domain repeat motifs adjacent to each other.

19. A CAR according to any one of claims 1 to 18, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, and 171.

20. A nucleic acid encoding an immunoreceptor or CAR according to any one of claims 1 to 19.

21. A cell comprising the nucleic acid according to claim 20.

22. I) The cell is an immune cell, preferably a B cell, macrophage, NK cell or T cell, more preferably a T cell, even more preferably CD4 + and / or CD8 + T cell, and II) the cell expresses an immunoreceptor or CAR according to any one of claims 1 to 19, III) the cell comprises a nucleic acid stably integrated into the genome, and / or IV) the nucleic acid contained in the cell is contained in an episomal vector, the cell according to claim 21.

23. A nucleic acid, a cell comprising the nucleic acid, an immunoreceptor, or a CAR according to any one of claims 1 to 22, for use in a method of treating cancer, an autoimmune disease, an infectious disease, or a degenerative disease.

24. the disease is cancer, and the cancer is a hematological cancer or a solid cancer, Optionally, the blood cancer is leukemia or lymphoma, preferably acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, Burkitt lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, or diffuse large B-cell lymphoma, Optionally, the solid cancer is breast cancer, colon cancer, lung cancer, pancreatic or prostate cancer, or glioblastoma, an immune receptor, CAR, nucleic acid or cell comprising a nucleic acid for use according to claim 23.

25. An antigen-binding protein, streptamer or aptamer capable of binding to an epitope comprised by a sequence consisting of at least one, preferably at least two, more preferably at least three repeats of the amino acid sequence of SEQ ID NO: 1, optionally wherein at least two repeats are adjacent to each other.

26. An antigen-binding protein, streptamer or aptamer according to claim 25, capable of binding to an immune receptor or CAR according to any one of claims 1 to 19.

27. An antigen-binding protein, streptamer or aptamer according to claim 26, capable of stimulating an immune receptor or CAR according to any one of claims 1 to 19.

28. An antigen-binding protein, streptamer or aptamer according to any one of claims 25 to 27, which is an antibody or fragment thereof, preferably a monoclonal antibody or fragment thereof.

29. a) A heavy chain variable region having at least 80%, preferably at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 19, preferably containing a CDR1 having the amino acid sequence of SEQ ID NO: 20, a CDR2 having the amino acid sequence of SEQ ID NO: 21, and a CDR3 having the amino acid sequence of SEQ ID NO: 22, and b) A light chain variable region having at least 80%, preferably at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 23, preferably containing a CDR1 having the amino acid sequence of SEQ ID NO: 24, a CDR2 having the amino acid sequence of SEQ ID NO: 25, and a CDR3 having the amino acid sequence of SEQ ID NO: 26 comprising an antigen-binding protein according to any one of claims 25 to 28.

30. Use of an antigen-binding protein, streptamer or aptamer according to any one of claims 25 to 29 for the purification, detection, depletion, stimulation, expansion or enrichment of cells expressing an immune receptor or CAR according to any one of claims 1 to 19.

31. A method comprising the step of binding an antigen-binding protein, streptamer or aptamer to a cell expressing an immune receptor or CAR according to any one of claims 1 to 19, preferably wherein the binding is specific binding to the IgG3 central hinge repeat domain contained in the immune receptor or CAR, and / or wherein the antigen-binding protein, streptamer or aptamer is an antigen-binding protein, streptamer or aptamer according to any one of claims 25 to 29.

32. A method for purifying a cell expressing an immune receptor or CAR according to any one of claims 1 to 19, A) Optionally obtaining cells expressing a chimeric antigen receptor; B) Incubating the cells with a primary antibody, streptamer or aptamer which is the antigen-binding protein, streptamer or aptamer according to any one of claims 25 to 29 under conditions that allow an antibody, streptamer or aptamer to bind to the immune receptor or CAR expressed by the cells; C) Separating antibody-bound cells, streptamer-bound cells or aptamer-bound cells from unbound cells to obtain purified cells The method according to claim 31, comprising the above steps.

33. Step C comprises incubating the cells of step B with an entity capable of binding to an antibody, streptamer or aptamer, I) The entity is preferably a secondary antibody labeled with a fluorescent marker; or beads, more preferably magnetic beads; II) The primary antibody, streptamer or aptamer is labeled, and the label is preferably a tag or a fluorescent dye; III) The separation in step C is carried out by means of MACS or FACS, and / or IV) The separation is carried out using a streptamer or aptamer. The purification method according to claim 32.

34. A method for depleting a cell expressing an immune receptor or CAR according to any one of claims 1 to 19, A) Optionally obtaining cells expressing an immune receptor or CAR; B) Incubating the cells with an antigen-binding protein, streptamer, or aptamer according to any one of claims 25 to 29 conjugated to a cytotoxic molecule; The method according to claim 31, which comprises the above steps.

35. A method for a) stimulating and / or b) expanding cells expressing an immune receptor or CAR according to any one of claims 1 to 19, comprising: A) Optionally obtaining cells expressing an immune receptor or CAR; B) Optionally incubating the cells with an antigen-binding protein, streptamer, or aptamer according to any one of claims 25 to 29, wherein the antigen-binding protein, streptamer, or aptamer is bound to a solid phase or expressed on the surface of the cells; The method according to claim 31, which comprises the above steps.

36. I) The solid phase is a tissue culture surface or beads, preferably magnetic beads, and / or II) The solid phase is a scaffold made of a polymer, preferably starch or sugar; The stimulation or expansion method according to claim 35.

37. A method for concentrating cells expressing an immune receptor or CAR according to any one of claims 1 to 19, comprising: A) Stimulating and / or expanding the cells by the method according to claim 35 or 36; B) Purifying the cells of step A by the method according to claim 32 or 33; The method according to claim 31, which comprises the above steps.

38. The method or use according to any one of claims 30 to 37, which is an in vitro method or use.

39. The method or use according to any one of claims 30 to 38, which does not include a method for treating the body of a human or animal by surgery or therapy or a diagnostic method performed on the body of a human or animal.

40. A pharmaceutical composition comprising cells expressing an antigen-binding protein, streptamer, or aptamer according to any one of claims 25 to 29, or a chimeric antigen receptor comprising all or part of the antigen-binding protein, streptamer, or aptamer, optionally further comprising a pharmaceutically acceptable carrier and / or excipient.

41. An antigen-binding protein, streptamer or aptamer according to any one of claims 25 to 29, or a chimeric antigen receptor expressing the antigen-binding protein, streptamer or aptamer, or all or part thereof, or a pharmaceutical composition according to claim 40, wherein administering to a subject in need thereof a cell expressing the antigen-binding protein, streptamer or aptamer bound to a cytotoxic molecule, or the chimeric antigen receptor comprising all or part of the antigen-binding protein, streptamer or aptamer, for use in the treatment of depletion of cells expressing an immunoreceptor or CAR according to any one of claims 1 to 19, the antigen-binding protein, streptamer or aptamer, or the cell, or the pharmaceutical composition.

42. A kit comprising an immunoreceptor or CAR according to any one of claims 1 to 19 and an antigen-binding protein, streptamer or aptamer according to any one of claims 25 to 27.

43. A bispecific antibody comprising one or more IgG3 central hinge repeat domain motifs.

44. One or more IgG3 central hinge domain repeat motifs are I) derived from the human IgG3 central hinge and / or II) consist of the amino acid sequence of SEQ ID NO: 1 and / or III) have reduced immunogenicity compared to repeats of the IgG1 hinge domain and / or IgG4 hinge domain, the bispecific antibody according to claim 43.

45. I) does not include all or part of the sequence of the lower hinge domain of the human IgG3 hinge domain, II) [A-B n ​ (wherein A is the amino acid sequence of SEQ ID NO: 2, B is the IgG3 central hinge domain repeat motif, which has the amino acid sequence of SEQ ID NO: 1, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, preferably an integer between 1 and 15, more preferably an integer between 1 and 10, even more preferably an integer between 1 and 5, and most preferably an integer between 3 and 5) and an amino acid sequence having at least 80% sequence identity, preferably at least 90% sequence identity, or most preferably 100% sequence identity, III) comprising 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 IgG3 central hinge domain repeat motifs, and / or IV) The bispecific antibody according to claim 43 or 44, which has reduced immunogenicity compared to a second bispecific antibody that is different from the first bispecific antibody in that it does not contain the one or more IgG3 central hinge domain repeat motifs.

46. The immune receptor has an amino acid sequence having 100% sequence identity with the amino acid sequence of [A-B n , and the bispecific antibody according to any one of claims 43 to 45.

47. The bispecific antibody according to claim 45 or 46, wherein n is an integer between 1 and 10.

48. The immune receptor according to claim 45 or 46, wherein n is an integer between 1 and 5.

49. The immune receptor according to claim 45 or 46, wherein n is an integer between 3 and 5.

50. The bispecific antibody according to any one of claims 43 to 49, comprising at least two, preferably at least three, IgG3 central hinge repeat domain motifs, and optionally at least two of the IgG3 central hinge repeat domain motifs are adjacent to each other.

51. The immune receptor, CAR, nucleic acid, cell, method, pharmaceutical composition, kit or bispecific antibody according to any one of claims 1 to 24 or 31 to 50, wherein the IgG3 central hinge repeat domain motif is not a mouse IgG3 central hinge repeat domain.

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