Immunoglobulin single variable domains targeting ceacam5

Abstract

The present technology provides polypeptides that bind to CEACAM5. The present technology also provides nucleic acids, vectors and compositions.

Description

[0001]IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS TARGETING CEACAM51 Field of the present technologyThe present technology relates to immunoglobulin single variable domains (ISVDs) targeting Carcino-embryonic antigen Cell Adhesion Molecule 5 (CEACAM5) and more in particular to polypeptides and constructs that comprise or essentially consist of one or more such ISVDs. It also relates to nucleic acid molecules encoding the ISVDs and polypeptides and vectors comprising the nucleic acids, and to compositions comprising the ISVD, polypeptide, nucleic acid or vector. The present technology further relates to these products for use in a method of treating a subject suffering from cancer. The present technology also relates to methods of producing these products.2 Technological BackgroundCEACAM5, also known as carcinoembryonic antigen-related cell adhesion molecule 5, is a member of the carcinoembryonic antigen (CEA) family of highly glycosylated cell surface glycoproteins involved in cell adhesion and signalling. Members of this family are structurally similar and consist of varying numbers of immunoglobulin variable (IgV-like) and constant (IgC-like) domains in their extracellular regions. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5, also known as CEA) has an N-terminal IgV-like domain followed by six IgC-like domains and normally functions as an adhesion molecule but it also has roles in regulating differentiation, immune modulation, and inhibitinganoikis (Thomas J. et al., “CEACAMS 1, 5, and 6 in disease and cancer: interactions with pathogens”,Genes Cancer, 2023, 14:12-29). CEACAM5 plays an important role in clinical routine as a tumour marker for several tumour entities, including gastrointestinal and respiratory malignancies because it is weakly expressed in normal epithelial tissues and expression is restricted to the apical / luminal surface of epithelial cell membranes, making it inaccessible to antibodies, but is highly expressed in several epithelial tumour types, such as tumours of the gastrointestinal tract, lung, breast, pancreas, gallbladder, bladder or ovary (see, e.g., Hammarström S., “The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues”, Semin Cancer Biol.1999 Apr;9(2):67-81.; Blumenthal R.D., Hansen H. J, Goldenberg D.M, “Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)”, Cancer Res 1 October 2005; 65 (19): 8809–8817; Shirasu, N. & Kuroki, M. CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5 (Carcinoembryonic antigen)), Atlas Genet Cytogenet Oncol Haematol.2018). In cancer cells, CEACAM5 loses its polarized expression and is thought to facilitate tumorigenesis and metastasis by acting as homophilic and heterophilic adhesion molecule which can thus promote cell adhesion and migration and allow for immune evasion of cancer cells. Moreover, CEACAM5 was also found to prevent anoikis (induction of apoptosis in cells upon loss of attachment to the extracellular matrix (ECM) and neighbouring cells), which is thought to promote metastasis(Thomas J. et al., Genes Cancer, 2023, 14:12-29).Due to its distinct expression pattern CEACAM5 in tumor versus normal tissues, CEACAM5 is an attractive therapeutic target, and monoclonal antibodies targeting CEACAM5 have been developed. For instance, antibodies targeting the A1B1 domains shared by CEACAM5 and CEACAM6 were shown to affect cell migration, cell invasion, and cell adhesion and affect metastasis and host survival (Blumenthal R.D., Hansen H. J, Goldenberg D.M., “Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)”, Cancer Res 1 October 2005; 65 (19): 8809–8817). In addition, there are ongoing phase 2 and phase 3 clinical trials of the potential first-in-class CEACAM5-targeted agent tusamitamab ravtansine (formerly SAR408701), which is a humanized monoclonal antibody covalently linked to a cytotoxic maytansinoid. In the phase I dose - escalation study, a favorable safety profile signals of antitumor activity were observed (Gazzah A, Bedard PL, Hierro C, Kang YK, Abdul Razak A, Ryu MH, Demers B, Fagniez N, Henry C, Hospitel M, Soria JC, Tabernero J., “Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study”, Ann Oncol.2022 Apr;33(4):416-425). However, at least some of the antibodies developed lack specificity for related antigens due to homologies within the CEACAM family, as antibodies that bind to repetitive epitopes of CEACAM5 present in the different immunoglobulin domains show cross-reactivity to other CEACAM members such as CEACAM1, CEACAM6, CEACAM7 or CEACAM8 and lack specificity for CEACAM5. Consequently, for CEA-targeted therapies, the specificity of the anti-CEACAM5 antibody is desired so that it binds to human CEACAM5-expressing tumour cells but not to some normal tissues expressing the other CEACAM members. On the other hand, to facilitate pre-clinical development of potential therapeutic molecules, cross-reactivity of the anti-CEACAM5 antibody to a therapeutic model such as cynomolgus monkey is desired. In addition, another disadvantage of the known anti-CEACAM5-antibodies, include their manufacturing process and storage (e.g., low efficiency of production, low product quality) as well as their therapeutic applications, as antibodies in general, due to their size, there is a chance they may not be able to penetrate diseased tissue effectively. There is still a need for improved small-molecule biologics to CEACAM5. Such small-molecule biologics are also useful for combining with other (cancer)-target binders in a single chain, while maintaining a relatively small size, high affinity, potency and / or efficacy, in addition to good manufacturing yields. Furthermore, the biological drug should show safety, convenience, patient compliance and improve patients’ quality of life.3 Summary of the present technologyIn some embodiments, the present technology relates to immunoglobulin single variable domains (ISVDs) specifically targeting CEACAM5. In some embodiments, the present technology relates to high affinity immunoglobulin single variable domains specifically targeting CEACAM5. In some embodiments, the present technology relates to high potency immunoglobulin single variable domains specifically targeting CEACAM5. In some embodiments, the present technology relates to high efficacy immunoglobulin single variable domains specifically targeting CEACAM5. In some embodiments the present technology relates to immunoglobulin single variable domains (ISVDs) specifically targeting different epitopes on CEACAM5 that can be used in different applications, e.g., in the preparation of biparatopic constructs. Targeting CEACAM5 with a biologic that is small (in size), such as a monovalent or bivalent immunoglobulin single variable domain and keeping a high affinity may be advantageous in certain applications where a very small binder is desired. Small binders may be advantageous, e.g., for penetration in the tumor environment, or when additional binders for other (tumor) targets are implicated in the same construct, facilitating manufacturing and further handling of the therapeutic compound. The immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GLTFSTYTMG (SEQ ID NO: 1);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GLTFSTYTMG (SEQ ID NO: 1);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences GLTFSTYTMG (SEQ ID NO: 1); and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIIWSGSNTY (SEQ ID NO: 2);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of AIIWSGSNTY (SEQ ID NO: 2); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of AIIWSGSNTY (SEQ ID NO: 2); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein theamino acid residue X is selected from N, A, F, G, I, L, Y or H; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 3;or^ CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 33;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYAY(SEQ ID NO: 249); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYFY(SEQ ID NO: 250), or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYGY(SEQ ID NO: 251); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYIY(SEQ ID NO: 254); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYLY(SEQ ID NO: 252); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYYY(SEQ ID NO: 253). In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 8, 31, 32, or 150-159. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 8, 31, 32, or 150-159. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GX1TFSX2YAX3G (SEQ ID NO: 231), wherein the aminoacid residue X1is selected from R or H, the amino acid residue X2is selected from E or D and the amino acid residue X3is selected from L or M; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GX1TFSX2YAX3G (SEQ ID NO: 231), wherein the amino acid residueX1 is selected from R or H, the amino acid residue X2 is selected from E or D and the amino acid residue X3 is selected from L or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences GX1TFSX2YAX3G (SEQ ID NO: 231), wherein the amino acid residue X1is selected from R or H, the amino acid residue X2is selected from E or D and the amino acid residue X3is selected from L or M; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AINWGGXWTY (SEQ ID NO: 232), wherein the aminoacid residue X is selected from T, G or S; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of AINWGGXWTY (SEQ ID NO: 232), wherein the amino acid residueX is selected from T, G or S; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of AINWGGXWTY (SEQ ID NO: 232), wherein the amino acid residueX is selected from T, G or S); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein theamino acid residue X1 is selected from S, P or L, the amino acid residue X2 is selected from N or S, the amino acid residue X3 is selected from P or A; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), the amino acid residue X1 is selected from S, P or L, the amino acid residue X2is selected from N or S, the amino acid residue X3is selected from P or A; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein the amino acid residue X1 is selected from S, P or L, the amino acid residue X2 is selected from N or S, the amino acid residue X3 is selected from P or A. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 9;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:10; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 11;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 234;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:235; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 236.or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 234;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:238; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 239.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 16, 39, 40, 120, 121, 135-149. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 16, 39, 40, 120, 121, 135-149. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GRTFXSYDMG (SEQ ID NO: 242), wherein the amino acidresidue X is selected from N, E, G, P, S or T; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTFXSYDMG (SEQ ID NO: 242), wherein the amino acid residue X isselected from N, E, G, P, S or T; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTFXSYDMG (SEQ ID NO: 242), wherein the amino acid residue X isselected from N, E, G, P, S or T; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIRWSAGSTV (SEQ ID NO: 256);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIRWSAGSTV (SEQ ID NO: 256); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIRWSAGSTV (SEQ ID NO: 256); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRPSFRPLSTYWKDYDN (SEQ ID NO: 257);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRPSFRPLSTYWKDYDN (SEQ ID NO: 257); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRPSFRPLSTYWKDYDN (SEQ ID NO: 257). The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 255;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 284;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 285;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 286;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 287;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 288;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 114, 175-208. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 114, 175-208. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acidresidue X is selected from R or G; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acid residue X isselected from R or G; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acid residue X isselected from R or G; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the aminoacid residue X1 is selected from A or T, wherein the amino acid residue X2 isselected from L or I, wherein the amino acid residue X3 is selected from G or E andwherein the amino acid residue X4 is selected from T or I;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residueX1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I,wherein the amino acid residue X3 is selected from G or E and wherein the aminoacid residue X4is selected from T or I; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence the amino acid X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the aminoacid residue X1 is selected from A or T, wherein the amino acid residue X2 is selectedfrom L or I, wherein the amino acid residue X3 is selected from G or E and whereinthe amino acid residue X4 is selected from T or I; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1 is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or Rand wherein the amino acid residue X4 is selected from N or K, and wherein theamino acid residue X5 is selected from F or Y; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acidresidue X1 is selected from Q or E, wherein the amino acid residue X2 is selectedfrom Y or F, wherein the amino acid residue X3 is selected from T or R and whereinthe amino acid residue X4 is selected from N or K, and wherein the amino acidresidue X5 is selected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acidresidue X1 is selected from Q or E, wherein the amino acid residue X2 is selectedfrom Y or F, wherein the amino acid residue X3 is selected from T or R and whereinthe amino acid residue X4 is selected from N or K, and wherein the amino acidresidue X5 is selected from F or Y. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 321;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 322;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 323;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 324;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 325;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 326;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 324;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 325;and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 327.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 115-117, 160-170. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 115-117, 160-170. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GLTFSTYTXG (SEQ ID NO: 333), wherein the amino acidresidue X is selected from V or M;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GLTFSTYTXG (SEQ ID NO: 333), wherein the amino acid residue Xis selected from V or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences GLTFSTYTXG (SEQ ID NO: 333), wherein the amino acid residue X isselected from V or M; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SX1IX2SGSNTX3 (SEQ ID NO: 335); wherein the aminoacid residue X1 is selected from I or M, wherein the amino acid residue X2 isselected from W or Y, and wherein the amino acid residue X3 is selected from Vor L; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence SX1IX2SGSNTX3 (SEQ ID NO: 335); wherein the amino acid residue X1is selected from I or M, wherein the amino acid residue X2 is selected from W or Y,and wherein the amino acid residue X3 is selected from V or L;c) amino acid sequences that 3, 2, or 1 amino acid difference with the amino acidsequence SX1IX2SGSNTX3 (SEQ ID NO: 335); wherein the amino acid residue X1 isselected from I or M, wherein the amino acid residue X2 is selected from W or Y,and wherein the amino acid residue X3 is selected from V or L; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of QHFGPX1SLTTRGYX2Y (SEQ ID NO: 338); wherein theamino acid residue X1 is selected from V or I, and wherein the amino acid residueX2 is selected from Y or F; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of QHFGPX1SLTTRGYX2Y (SEQ ID NO: 338); wherein the amino acidresidue X1 is selected from V or I, and wherein the amino acid residue X2 is selectedfrom Y or F; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of QHFGPX1SLTTRGYX2Y (SEQ ID NO: 338); wherein the amino acidresidue X1 is selected from V or I, and wherein the amino acid residue X2 is selectedfrom Y or F. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 336;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 339;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 334;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 337;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 340.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 118-119, 171-174. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 118-119, 171-174. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GRTFSDXAMG (SEQ ID NO: 356), wherein the amino acidresidue X is selected from F or Y;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTFSDXAMG (SEQ ID NO: 356), wherein the amino acid residue X isselected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTFSDXAMG (SEQ ID NO: 356), wherein the amino acid residue X isselected from F or Y; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence AINWSGGWTY (SEQ ID NO: 357);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AINWSGGWTY (SEQ ID NO: 357); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AINWSGGWTY (SEQ ID NO: 357);and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence SSDYAGGRSTGYXY (SEQ ID NO: 358); wherein the aminoacid residue X is selected from A or D; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence SSDYAGGRSTGYXY (SEQ ID NO: 358); wherein the amino acid residueX is selected from A or D; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence SSDYAGGRSTGYXY (SEQ ID NO: 358); wherein the amino acid residueX is selected from A or D. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 359;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 357;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 360;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 234;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 357;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 361.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 122 or 123. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 122 or 123. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GRTFNINEYHLA (SEQ ID NO: 363);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTFNINEYHLA (SEQ ID NO: 363); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTFNINEYHLA (SEQ ID NO: 363); and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence AIWWSTGNKI (SEQ ID NO: 364);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIWWSTGNKI (SEQ ID NO: 364); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIWWSTGNKI (SEQ ID NO: 364); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRFSFRPLSTYWKDYDN (SEQ ID NO: 365);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRFSFRPLSTYWKDYDN (SEQ ID NO: 365); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRFSFRPLSTYWKDYDN (SEQ ID NO: 365). The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 363;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 364;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 365.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NO: 124. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NO: 124. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GRTLNDYHMA (SEQ ID NO: 368);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTLNDYHMA (SEQ ID NO: 368);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTLNDYHMA (SEQ ID NO: 368);and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence AIWWSTGNRI (SEQ ID NO: 369);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIWWSTGNRI (SEQ ID NO: 369); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIWWSTGNRI (SEQ ID NO: 369); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRFSFRPLSTYWKDYDI (SEQ ID NO: 370);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRFSFRPLSTYWKDYDI (SEQ ID NO: 370);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRFSFRPLSTYWKDYDI (SEQ ID NO: 370).The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 368;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 369;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 370.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NO: 125. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NO: 125. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GDXLNSYHMA (SEQ ID NO: 373), wherein the aminoacid residue X is selected from T or N; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GDXLNSYHMA (SEQ ID NO: 373), wherein the amino acid residue X is selected from T or N; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences of GDXLNSYHMA (SEQ ID NO: 373), wherein the amino acid residue X is selected from T or N; and- CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence AIWWSTGNXI (SEQ ID NO: 374), wherein the amino acidresidue X is selected from A or T; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIWWSTGNXI (SEQ ID NO: 374), wherein the amino acid residue X is selected from A or T; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIWWSTGNXI (SEQ ID NO: 374), wherein the amino acid residue X is selected from A or T); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRFXFRPLSTYWKDYDN (SEQ ID NO: 375); wherein theamino acid residue X is selected from S or Q; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRFXFRPLSTYWKDYDN (SEQ ID NO: 375); wherein the amino acid residue X is selected from S or Q; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRFXFRPLSTYWKDYDN (SEQ ID NO: 375); wherein the amino acid residue X is selected from S or Q. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 376;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 377;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 365;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 378;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 379;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 380. In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 126 or 127. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 126 or 127. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GX1TFSX2YAMG (SEQ ID NO: 386), wherein the amino acidresidue X1 is selected from G or R, and wherein the amino acid residue X2 is selected from S or N; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GX1TFSX2YAMG (SEQ ID NO: 386), wherein the amino acid residue X1is selected from G or R, and wherein the amino acid residue X2 is selected from S or N; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences GX1TFSX2YAMG (SEQ ID NO: 386), wherein the amino acid residue X1 is selected from G or R, and wherein the amino acid residue X2 is selected from S or N; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GMSWSGGSTH (SEQ ID NO: 387);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GMSWSGGSTH (SEQ ID NO: 387); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GMSWSGGSTH (SEQ ID NO: 387); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GXNPMGPIATRPSVHDY (SEQ ID NO: 388); wherein theamino acid residue X is selected from Q or R;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GXNPMGPIATRPSVHDY (SEQ ID NO: 388); wherein the amino acid residue X is selected from Q or R; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GXNPMGPIATRPSVHDY (SEQ ID NO: 388); wherein the amino acid residue X is selected from Q or R. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 389;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 387;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 390;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 391;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 387;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 392.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 128, 129, or 134. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 128, 129, or 134. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GGTVSTYTMG (SEQ ID NO: 397);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GGTVSTYTMG (SEQ ID NO: 397);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GGTVSTYTMG (SEQ ID NO: 397);and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence SIIWSGSTTV (SEQ ID NO: 398);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence SIIWSGSTTV (SEQ ID NO: 398); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence SIIWSGSTTV (SEQ ID NO: 398);and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QHFGPVSQTTKGYFY (SEQ ID NO: 399);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QHFGPVSQTTKGYFY (SEQ ID NO: 399);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QHFGPVSQTTKGYFY (SEQ ID NO: 399).The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 397;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 398;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 399.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 130. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 130. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein:- CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GRTLNDYHMA (SEQ ID NO: 368);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTLNDYHMA (SEQ ID NO: 368);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTLNDYHMA (SEQ ID NO: 368);and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence AIWWSTGNTI (SEQ ID NO: 379);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIWWSTGNTI (SEQ ID NO: 379);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIWWSTGNTI (SEQ ID NO: 379);and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRFSFRPLSTYWKDYDN (SEQ ID NO: 365);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRFSFRPLSTYWKDYDN (SEQ ID NO: 365);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRFSFRPLSTYWKDYDN (SEQ ID NO: 365).The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 368;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 379;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 365.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NO: 131. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NO: 131. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GX1TFSX2X3AX4G (SEQ ID NO: 530); wherein the amino acidresidue X1is selected from R or H; wherein the amino acid residue X2is selected from E or D; wherein the amino acid residue X3is selected from F or Y; and wherein the amino acid residue X4is selected from L or M; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GX1TFSX2X3AX4G (SEQ ID NO: 530); wherein the amino acid residue X1 is selected from R or H; wherein the amino acid residue X2 is selected from E or D; wherein the amino acid residue X3is selected from F or Y; and wherein the amino acid residue X4is selected from L or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GX1TFSX2X3AX4G (SEQ ID NO: 530); wherein the amino acid residue X1 is selected from R or H; wherein the amino acid residue X2 is selected from E or D; wherein the amino acid residue X3 is selected from F or Y; and wherein the amino acid residue X4 is selected from L or M; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence AINWX1GX2WTY (SEQ ID NO: 531); wherein the amino acidresidue X1is selected from G or S; and wherein the amino acid residue X2is selected from T, G or S; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AINWX1GX2WTY (SEQ ID NO: 531), wherein the amino acid residue X1is selected from G or S; and wherein the amino acid residue X2is selected from T, G or S; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AINWX1GX2WTY (SEQ ID NO: 531), wherein the amino acid residue X1is selected from G or S; and wherein the amino acid residue X2is selected from T, G or S; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence SX1DYAGGX2X3TGYX4Y (SEQ ID NO: 532); wherein theamino acid residue X1 is selected from S, P or L; wherein the amino acid residue X2 is selected from N, R or S; wherein the amino acid residue X3 is selected from P or S; and wherein the amino acid residue X4 is selected from P, D or A; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SX1DYAGGX2X3TGYX4Y (SEQ ID NO: 532); wherein the amino acid residue X1is selected from S, P or L; wherein the amino acid residue X2is selected from N, R or S; wherein the amino acid residue X3is selected from P or S; and wherein the amino acid residue X4 is selected from P, D or A; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SX1DYAGGX2X3TGYX4Y (SEQ ID NO: 532); wherein the amino acid residue X1is selected from S, P or L; wherein the amino acid residue X2is selected from N, R or S; wherein the amino acid residue X3is selected from P or S; and wherein the amino acid residue X4is selected from P, D or A. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 9;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:10; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 11,or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 234;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:235; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 236,;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 234;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:238; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 239,or^ CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 359;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 357;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 360,or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 234;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 357;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 361.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 16, 39, 40, 120, 121, 122, 123, 135-149. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 16, 39, 40, 120, 121, 122, 123, 135-149. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GX1X2X3X4X5YX6X7X8 (SEQ ID NO: 536); wherein the aminoacid residue X1 is selected from R or D, the amino acid residue X2 is selected from N or T; wherein the amino acid residue X3is selected from F or L; wherein the amino acid residue X4is selected from N, E, G, P, S, or T; wherein the amino acid residue X5 is selected from S , D, or the stretch of the following amino acids: I, N and E; wherein the amino acid residue X6is selected from D or H; wherein the amino acid residue X7 is selected from L or M; and wherein the amino acid residue X8 is selected from A or G; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GX1X2X3X4X5YX6X7X8(SEQ ID NO: 536); wherein the amino acid residue X1is selected from R or D, the amino acid residue X2is selected from N or T; wherein the amino acid residue X3is selected from F or L; wherein the amino acid residue X4 is selected from N, E, G, P, S, or T; wherein the amino acid residue X5 is selected from S, D, or the stretch of the following amino acids: I, N and E; wherein the amino acid residue X6 is selected from D or H; wherein the amino acid residue X7 is selected from L or M; and wherein the amino acid residue X8 is selected from A or G; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GX1X2X3X4X5YX6X7X8 (SEQ ID NO: 536); wherein the amino acid residue X1is selected from R or D, the amino acid residue X2is selected from N or T; wherein the amino acid residue X3is selected from F or L; wherein the amino acid residue X4is selected from N, E, G, P, S, or T; wherein the amino acid residue X5is selected from S, E, D, or the stretch of the following amino acids: I, N and E; wherein the amino acid residue X6 is selected from D or H; wherein the amino acid residue X7 is selected from L or M; and wherein the amino acid residue X8 is selected from A or G; and- CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIX1WSX2GX3X4X5 (SEQ ID NO: 537); wherein theamino acid residue X1is selected from R or W; the amino acid residue X2is selected from A or T; wherein the amino acid residue X3is selected from S or N; wherein the amino acid residue X4is selected from K, R, A or T; and wherein the amino acid residue X5is selected from I or V; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIX1WSX2GX3X4X5 (SEQ ID NO: 537); wherein the amino acid residue X1 is selected from R or W; the amino acid residue X2 is selected from A or T; wherein the amino acid residue X3 is selected from S or N; wherein the amino acid residue X4 is selected from K, R, A or T; and wherein the amino acid residue X5 is selected from I or V; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIX1WSX2GX3X4X5(SEQ ID NO: 537); wherein the amino acid residue X1 is selected from R or W; the amino acid residue X2 is selected from A or T; wherein the amino acid residue X3 is selected from S or N; wherein the amino acid residue X4 is selected from K, R, A or T; and wherein the amino acid residue X5 is selected from I or V; and- CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRX1X2FRPLSTYWKDYDX3 (SEQ ID NO: 538); wherein theamino acid residue X1 is selected from F or P; wherein the amino acid residue X2 is selected from Q or S; and wherein the amino acid residue X3 is selected from I or N; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRX1X2FRPLSTYWKDYDX3(SEQ ID NO: 538); wherein the amino acid residue X1is selected from F or P; wherein the amino acid residue X2is selected from Q or S; and wherein the amino acid residue X3is selected from I or N; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRX1X2FRPLSTYWKDYDX3 (SEQ ID NO: 538); wherein the amino acid residue X1 is selected from F or P; wherein the amino acid residue X2 is selected from Q or S; and wherein the amino acid residue X3is selected from I or N. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 255;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 284;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 285;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 286;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 287;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 288;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 256;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 257;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 363;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 364;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 365;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 368;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 369;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 370;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 376;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 377;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 365;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 378;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 379;and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 380.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 114, 124-127, 175-208. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 114, 124-127, 175-208. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GX1TX2STYTX3G (SEQ ID NO: 541); wherein the aminoacid residue X1 is selected from G or L; wherein the amino acid residue X2 is selected from V or F; and wherein the amino acid residue X3 is selected from V or M; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GX1TX2STYTX3G (SEQ ID NO: 541); wherein the amino acid residue X1 is selected from G or L; wherein the amino acid residue X2 is selected from V or F; and wherein the amino acid residue X3 is selected from V or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GX1TX2STYTX3G (SEQ ID NO: 541); wherein the amino acid residue X1 is selected from G or L; wherein the amino acid residue X2is selected from V or F, and wherein the amino acid residue X3is selected from V or M; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of X1X2IX3SGSX4TX5 (SEQ ID NO: 542); wherein the aminoacid residue X1 is selected from S or A; wherein the amino acid residue X2 is selected from I or M; wherein the amino acid residue X3 is selected from W or Y; wherein the amino acid residue X4 is selected from N or T; and wherein the amino acid residue X5is selected from V, Y or L; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence X1X2IX3SGSX4TX5 (SEQ ID NO: 542); wherein the amino acid residue X1 is selected from S or A; wherein the amino acid residue X2 is selected from I or M; wherein the amino acid residue X3 is selected from W or Y; wherein the amino acid residue X4 is selected from N or T; and wherein the amino acid residue X5 is selected from V, Y or L; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence X1X2IX3SGSX4TX5 (SEQ ID NO: 542); wherein the amino acid residue X1 is selected from S or A; wherein the amino acid residue X2 is selected from I or M; wherein the amino acid residue X3is selected from W or Y; wherein the amino acid residue X4is selected from N or T; and wherein the amino acid residue X5is selected from V, Y or L; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QHFGPX1X2X3TTX4GYX5Y (SEQ ID NO: 543); wherein theamino acid residue X1is selected from V or I; the amino acid residue X2is selected from S or G; wherein the amino acid residue X3is selected from L or Q; the amino acid residue X4is selected from R or K; and wherein the amino acid residue X5is selected from N, A, F, G, I, L, Y or H; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QHFGPX1X2X3TTX4GYX5Y (SEQ ID NO: 543); wherein the amino acid residue X1 is selected from V or I; the amino acid residue X2 is selected from S or G; wherein the amino acid residue X3 is selected from L or Q; the amino acid residue X4is selected from R or K; and wherein the amino acid residue X5is selected from N, A, F, G, I, L, Y or H; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of QHFGPX1X2X3TTX4GYX5Y (SEQ ID NO: 543); wherein the amino acid residue X1 is selected from V or I; the amino acid residue X2 is selected from S or G; wherein the amino acid residue X3 is selected from L or Q; the amino acid residue X4is selected from R or K; and wherein the amino acid residue X5is selected from N, A, F, G, I, L, Y or H. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 336;and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 339,or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 334;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 337;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 340;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 3;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 33;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYAY(SEQ ID NO: 249); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYFY(SEQ ID NO: 250); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYGY(SEQ ID NO: 251), or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYIY(SEQ ID NO: 254); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYLY(SEQ ID NO: 252); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYYY(SEQ ID NO: 253); or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 397;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 398;and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 399.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 8, 31, 32, 118-119, 130, 150-159, 171- 174. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 8, 31, 32, 118-119, 130, 150-159, 171-174. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GITX1RGGSTH (SEQ ID NO: 578), wherein the amino acidresidue X1is selected from W and N; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GGITX1RGGSTH (SEQ ID NO: 578), wherein the amino acid residue X1 is selected from W and N;c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GITX1RGGSTH (SEQ ID NO: 578), wherein the amino acid residue X1 is selected from W and N; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1LX2PFX3PITX4X5PQRIX6Y (SEQ ID NO: 581), wherein theamino acid residue X1is selected from D and V, wherein the amino acid residue X2is selected from R and V, wherein the amino acid residue X3is selected from G, A, and F, wherein the amino acid residue X4 is selected from Q and T, wherein the amino acid residue X5 is selected from T and E, and wherein the amino acid residue X6 is selected from N and E; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of X1LX2PFX3PITX4X5PQRIX6Y (SEQ ID NO: 581), wherein the amino acid residue X1is selected from D and V, wherein the amino acid residue X2is selected from R and V, wherein the amino acid residue X3 is selected from G, A, and F, wherein the amino acid residue X4 is selected from Q and T, wherein the amino acid residue X5 is selected from T and E, and wherein the amino acid residue X6 is selected from N and E; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of X1LX2PFX3PITX4X5PQRIX6Y (SEQ ID NO: 581), wherein the amino acid residue X1is selected from D and V, wherein the amino acid residue X2is selected from R and V, wherein the amino acid residue X3is selected from G, A, and F, wherein the amino acid residue X4 is selected from Q and T, wherein the amino acid residue X5 is selected from T and E, and wherein the amino acid residue X6 is selected from N and E. In an specific embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected froma) the amino acid sequence GRTFDNX1AMG (SEQ ID NO: 593); wherein the amino acidresidue X1 is selected from H, L or E;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTFDNX1AMG (SEQ ID NO: 593); wherein the amino acid residue X1 is selected from H, L or E; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTFDNX1AMG (SEQ ID NO: 593); wherein the amino acid residue X1 is selected from H, L or E; and- CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GITX1RGGSTH (SEQ ID NO: 578), wherein the amino acidresidue X1 is selected from W and N; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GGITX1RGGSTH (SEQ ID NO: 578), wherein the amino acid residue X1is selected from W and N; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GITX1RGGSTH (SEQ ID NO: 578), wherein the amino acid residue X1 is selected from W and N; and- CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1LX2PFX3PITX4X5PQRIX6Y (SEQ ID NO: 581), wherein theamino acid residue X1is selected from D and V, wherein the amino acid residue X2is selected from R and V, wherein the amino acid residue X3is selected from G, A, and F, wherein the amino acid residue X4is selected from Q and T, wherein the amino acid residue X5 is selected from T and E, and wherein the amino acid residue X6 is selected from N and E; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of X1LX2PFX3PITX4X5PQRIX6Y (SEQ ID NO: 581), wherein the amino acid residue X1is selected from D and V, wherein the amino acid residue X2is selected from R and V, wherein the amino acid residue X3is selected from G, A, and F, wherein the amino acid residue X4 is selected from Q and T, wherein the amino acid residue X5is selected from T and E, and wherein the amino acid residue X6 is selected from N and E; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of X1LX2PFX3PITX4X5PQRIX6Y (SEQ ID NO: 581), wherein the amino acid residue X1is selected from D and V, wherein the amino acid residue X2is selected from R and V, wherein the amino acid residue X3 is selected from G, A, and F, wherein the amino acid residue X4 is selected from Q and T, wherein the amino acid residue X5 is selected from T and E, and wherein the amino acid residue X6 is selected from N and E. The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 582;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 583;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 584;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 585;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 586;or^ CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 587;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 587;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 588;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 589;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 594;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:580; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 582;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 595;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 582;or ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 596;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:579; and^ CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 582.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 548, 564-576. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 548, 564-576. In another embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 610;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 610; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 610. In a specific embodiment, the immunoglobulin single variable domain of the present technology comprises four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected froma) the amino acid sequence GFTFSSYDMS (SEQ ID NO: 611);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GFTFSSYDMS (SEQ ID NO: 611); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GFTFSSYDMS (SEQ ID NO: 611); and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence TINRGGSSTS (SEQ ID NO: 612);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GTINRGGSSTS (SEQ ID NO: 612); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence TINRGGSSTS (SEQ ID NO: 612); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GDHRGPWYN (SEQ ID NO: 610);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GDHRGPWYN (SEQ ID NO: 610); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acidsequence of GDHRGPWYN (SEQ ID NO: 610). The immunoglobulin single variable domain of the present technology may comprise four framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 611;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:612; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 610.In some embodiments, the immunoglobulin single variable domain of the present technology has an amino acid sequence with a sequence identity of more than 80%, more than 90% (such as more than 95% or even more then 99%) with one of SEQ ID NOs: 547, 549-563. In one embodiment, the polypeptide of the present technology comprises or consists of the amino acid sequence of SEQ ID NOs: 547, 549-563. In some embodiments, the immunoglobulin single variable domain of the present technology may essentially consist of a VHH, such as a humanized VHH, or a VH, such as a camelized VH, a human VH, a camelized human VH, a domain antibody, a single domain antibody, and / or a dAb. The present technology also relates to polypeptides and constructs comprising such immunoglobulin single variable domain, and optionally further comprising one or more other groups, residues, moieties or binding units, optionally linked via one or more linkers. The immunoglobulin single variable domains of the present technology and polypeptides and constructs comprising said immunoglobulin single variable domains showed a high binding affinity in FACS binding assay on and a high internalization efficacy in FACS internalization assay of BxPC-3 cell line expressing CEACAM5, and could be efficiently produced (e.g., in microbial hosts such asPichia, e.g., P. pastoris, or in E. coli). In one embodiment, the immunoglobulin single variable domain, polypeptide or construct of the present technology may further comprise one or more other groups, residues, moieties or binding units, optionally linked via one or more peptidic linkers, in which said one or more other groups, residues, moieties or binding units provide the ISVD, polypeptide or construct with increased half- life, compared to the corresponding ISVD, polypeptide or construct without said one or more other groups, residues, moieties or binding units. Said one or more other groups, residues, moieties or binding units that provide the ISVD, polypeptide or construct with increased half-life may be chosen from the group consisting of a polyethylene glycol molecule (PEG), serum proteins or fragments thereof, binding units that can bind to serum proteins, an Fc portion, and small proteins or peptides that can bind to serum proteins. The binding units that provide the ISVD, polypeptide or construct with increased half-life may be chosen from the group consisting of binding units that can bind to serum albumin (such as human serum albumin) or a serum immunoglobulin (such as IgG), e.g., human serum albumin. In one embodiment, the binding unit that can bind to serum albumin (such as human serum albumin) is an ISVD. In one embodiment, the ISVD binding to human serum albumin essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively), in which CDR1 is SEQ ID NO: 80, CDR2 is SEQ ID NO: 81, CDR3 is SEQ ID NO: 82. In one embodiment, the ISVD binding to human serum albumin comprises a sequence identity of more than 90% (such as 95%) with SEQ ID NO: 62. In one embodiment, the ISVD binding to human serum albumin comprises or consists of the amino acid sequence of SEQ ID NO: 62. In one embodiment, the ISVD binding to human serum albumin is selected from the group consisting of ALB8 (SEQ ID NO: 47), ALB23 (SEQ ID NO: 48), ALBX00001 (SEQ ID NO: 61) and ALB23002 (SEQ ID NO: 62). In one embodiment, the ISVD binding to human serum albumin is ALB23002 (SEQ ID NO: 62). Also provided is a nucleic acid molecule capable of expressing the immunoglobulin single variable domain or polypeptide of the present technology, a vector comprising the nucleic acid, and a composition comprising the polypeptide, nucleic acid or vector. Also provided is a (non-human) host or host cell comprising such a nucleic acid. Also provided is a method for producing an immunoglobulin single variable domain or polypeptide of the present technology, said method at least comprising the steps of: a) expressing, in a suitable host cell or (non-human) host organism or in another suitable expression system, a nucleic acid encoding the immunoglobulin single variable domain or polypeptide of the present technology; optionally followed by: b) isolating and / or purifying the ISVD or polypeptide. Also provided is a composition comprising at least one immunoglobulin single variable domain, polypeptide or construct of the present technology, or a nucleic acid encoding an immunoglobulin single variable or polypeptide of the present technology. The composition of the present technology is for use as a medicament. The composition can be a pharmaceutical composition which further comprises at least one pharmaceutically acceptable carrier, diluent or excipient and / or adjuvant, and optionally comprises one or more further pharmaceutically active polypeptides and / or compounds. The immunoglobulin single variable domain, polypeptide or construct of the present technology, a composition comprising the immunoglobulin single variable domain, polypeptide or construct, and a composition comprising a nucleic acid comprising a nucleotide sequence that encodes the immunoglobulin single variable domain or polypeptide can be used as a medicament. The immunoglobulin single variable domain, polypeptide, construct or composition of the present technology can be used in the treatment. More specifically, the immunoglobulin single variable, polypeptide, construct or composition can be used in the treatment of cancer. Accordingly, the present technology also encompasses a method of treating cancer. In some embodiments, the present technology encompasses a method of treating cancer, wherein said method comprises administering, to a subject in need thereof, a pharmaceutically active amount of an immunoglobulin single variable domain, polypeptide or construct of the present technology, a nucleic acid encoding an ISVD or polypeptide of the present technology or a composition comprising the same. Accordingly, the present technology also encompasses the use of an immunoglobulin single domain, polypeptide or construct of the present technology in the preparation of a pharmaceutical composition for treating cancer.4 Brief Description of DrawingsIn order to best describe the manner in which the above-described embodiments are implemented, as well as define other advantages and features of the disclosure, a more particular description is provided below and is illustrated in the appended drawings. Understanding that these drawings depict only exemplary embodiments of the invention and are thus not to be considered to be limiting in scope, the examples will be described and explained with additional specificity and detail through the use of the accompanying drawings in which: Figure 1: Characterization by flow cytometry of the binding of anti-CEACAM5 VHHs on MKN45 cells. The FACS assay was conducted with 3 dilutions of non-purified VHHs produced in E. coli as described in Example 8 (section 2.8.1). Figure 2: Quality check of unpurified VHH-HA-His produced in FreeStyle 293-F cells with SDS-PAGE. Following clones are shown: line 1: 14R04-02 ; line 2 : 14R04-03 ; line 3 : 14R04-04; line 4: 14R04- 05; line 5: 14R04-06; line 6: 14R04-07; line 7: 14R04-08; line 8: 14R04-09; line 9: 14R04-10; line 10: 14R04-11; line 11: 14R04-12; line 12: 14R04-13; line 13: 14R04-14; line 14: 14R04-15; line 15: 14R04-16; line 16: 14R04-17; line 17: 14R04-18; line 18: 14R04-19; line 19: 14R04-20; line 20: 14R04-21; line 21: 14R04-22.Figure 3A and 3B: EC50 determination of anti-CEACAM5 VHHs by ELISA on hCEACAM5 andcCEACAM5. The ELISA assay was conducted with serial dilutions of non-purified VHHs produced in FreeStyle 293-F cells.Figure 4A and 4B: Evaluation of the affinity constant (KD) and maximum binding capacity (Bmax) toMKN45 cell line by flow cytometry. The FACS assay was conducted with serial dilutions of non- purified VHHs produced in FreeStyle 293-F cells. Figure 5: EC50 determination of anti-CEACAM5 VHHs by ELISA on (A) hCEACAM5 and (B) hCEACAM6. Figure 6: Characterization by flow cytometry of the binding of anti-CEACAM5 VHHs on LS174T cells. Figure 7a and 7b: Evaluation of the internalization of VHHs on LS174T cell line. The ISVD applied to the cell line are indicated in the legend. pHrhodo: only the pHrhodo anti-Flag antibody was applied; IRR: an ISVD not binding to CEACAM5 was applied to the cell line. Figure 8: Detailed views of interactions between the A2-B2 domains of hCEACAM5 and ISVD T232000134. (A) Epitope-paratope key interacting residues between the A2-B2 domains of hCEACAM5 and T232000134, dotted line represents H-bond interactions (magenta) and salt bridges (dark gray). The residues from T232000134 are indicated with “VHH”. (B) Key interacting residues of paratope located at <3.8Å distance from the hCEACAM5, backbone is in blue, and residues are shown with side chains in Yellow. (C) Key interacting residues of epitope located at < 3.8Å distance from IVSD T232000134, interacting residues are shown in colored in light see green. Figure 9: Detailed views of interactions between the A2-B2 domains of hCEACAM5 and ISVD 2G08. (A) Epitope-paratope key interacting residues between the A2-B2 domains of hCEACAM5 and 2G08, dotted line represents H-bond interactions (dark gray). The residues from ISVD 2G08 are indicated with “VHH”. (B) Key interacting residues of paratope located at <3.8Å distance from the hCEACAM5, backbone is in brown, and residues are shown with side chains in Yellow. (C) Key interacting residues of epitope located at < 3.8Å distance from IVSD 2G08, interacting residues are shown in colored in light see brown.5 Detailed description of the present technology5.1 DefinitionsUnless indicated or defined otherwise, all terms used have their usual meaning in the art, which will be clear to the skilled person. Reference is for example made to the standard handbooks, such as Sambrook et al. (Molecular Cloning: A Laboratory Manual (2nd.Ed.) Vols.1-3, Cold Spring Harbor Laboratory Press, 1989), F. Ausubel et al. (Current protocols in molecular biology, Green Publishing and Wiley Interscience, New York, 1987), Lewin (Genes II, John Wiley & Sons, New York, N.Y., 1985), Old et al. (Principles of Gene Manipulation: An Introduction to Genetic Engineering (2nd edition) University of California Press, Berkeley, CA, 1981); Roitt et al. (Immunology (6th. Ed.) Mosby / Elsevier, Edinburgh, 2001), Roitt et al. (Roitt’s Essential Immunology (10th Ed.) Blackwell Publishing, UK, 2001), and Janeway et al. (Immunobiology (6th Ed.) Garland Science Publishing / Churchill Livingstone, New York, 2005), as well as to the general background art cited herein. Unless indicated otherwise, all methods, steps, techniques and manipulations that are not specifically described in detail can be performed and have been performed in a manner known per se, as will be clear to the skilled person. Reference is for example again made to the standard handbooks and the general background art mentioned herein and to the further references cited therein; as well as to for example the following reviews Presta (Adv. Drug Deliv. Rev.58 (5-6): 640- 56, 2006), Levin and Weiss (Mol. Biosyst. 2(1): 49-57, 2006), Irving et al. (J. Immunol. Methods 248(1-2): 31-45, 2001), Schmitz et al. (Placenta 21 Suppl. A: S106-12, 2000), Gonzales et al. (Tumour Biol. 26(1): 31-43, 2005), which describe techniques for protein engineering, such as affinity maturation and other techniques for improving the specificity and other desired properties of proteins such as immunoglobulins. The term “sequence” as used herein (for example in terms like “immunoglobulin sequence”, “antibody sequence”, “variable domain sequence”, “VHH sequence” or “protein sequence”), should generally be understood to include both the relevant amino acid sequence as well as nucleic acids or nucleotide sequences encoding the same, unless the context requires a more limited interpretation. Amino acid residues will be indicated according to the standard three-letter or one-letter amino acid code. Reference is made to Table A-2 on page 48 of WO 08 / 020079. A nucleic acid or amino acid is considered to be “(in) (essentially) isolated (form)” - for example, compared to the reaction medium or cultivation medium from which it has been obtained - when it has been separated from at least one other component with which it is usually associated in said source or medium, such as another nucleic acid, another protein / polypeptide, another biological component or macromolecule or at least one contaminant, impurity or minor component. In particular, a nucleic acid or amino acid is considered “(essentially) isolated” when it has been purified at least 2-fold, in particular at least 10-fold, more in particular at least 100-fold, and up to 1000-fold or more. A nucleic acid or amino acid that is “in (essentially) isolated form” is preferably essentially homogeneous, as determined using a suitable technique, such as a suitable chromatographical technique, such as polyacrylamide-gel electrophoresis. When a nucleotide sequence or amino acid sequence is said to “comprise” another nucleotide sequence or amino acid sequence, respectively, or to “essentially consist of” another nucleotide sequence or amino acid sequence, this may mean that the latter nucleotide sequence or amino acid sequence has been incorporated into the first mentioned nucleotide sequence or amino acid sequence, respectively, but more usually this generally means that the first mentioned nucleotide sequence or amino acid sequence comprises within its sequence a stretch of nucleotides or amino acid residues, respectively, that has the same nucleotide sequence or amino acid sequence, respectively, as the latter sequence, irrespective of how the first mentioned sequence has actually been generated or obtained (which may for example be by any suitable method described herein). By means of a non-limiting example, when a polypeptide is said to comprise an immunoglobulin single variable domain, this may mean that said immunoglobulin single variable domain sequence has been incorporated into the sequence of the polypeptide, but more usually this generally means that the polypeptide contains within its sequence the sequence of the immunoglobulin single variable domains irrespective of how said polypeptide has been generated or obtained. Also, when a nucleic acid or nucleotide sequence is said to comprise another nucleotide sequence, the first mentioned nucleic acid or nucleotide sequence is preferably such that, when it is expressed into an expression product (e.g., a polypeptide), the amino acid sequence encoded by the latter nucleotide sequence forms part of said expression product (in other words, that the latter nucleotide sequence is in the same reading frame as the first mentioned, larger nucleic acid or nucleotide sequence). By “(essentially) consist of” is meant that the later nucleic acid sequence or amino acid sequence, either is exactly the same as the polypeptide (e.g., the CDR region; the ISVD) or corresponds to the polypeptide (e.g., the CDR region; the ISVD) which has a limited number of amino acid residues, such as 1-20 amino acid residues, for example 1-10 amino acid residues and preferably 1-6 amino acid residues, such as 1, 2, 3, 4, 5 or 6 amino acid residues, added at the amino terminal end, at the carboxy terminal end, or at both the amino terminal end and the carboxy terminal end of the immunoglobulin single variable domain. For the purposes of comparing two or more amino acid sequences, the percentage of “sequence identity” between a first amino acid sequence and a second amino acid sequence may be calculated by dividing [the number of amino acid residues in the first amino acid sequence that are identical to the amino acid residues at the corresponding positions in the second amino acid sequence] by [the total number of amino acid residues in the first amino acid sequence] and multiplying by [100%], in which each deletion, insertion, substitution or addition of an amino acid residue in the second amino acid sequence - compared to the first amino acid sequence - is considered as a difference at a single amino acid residue (i.e., at a single position). Usually, for the purpose of determining the percentage of “sequence identity” between two amino acid sequences in accordance with the calculation method outlined hereinabove, the amino acid sequence with the greatest number of amino acid residues will be taken as the “first” amino acid sequence, and the other amino acid sequence will be taken as the “second” amino acid sequence. An “amino acid difference” as used herein refers to a deletion, insertion or substitution of a single amino acid residue vis-à-vis a reference sequence. In one embodiment, an “amino acid difference” is a substitution. In one embodiment, amino acid substitutions are conservative substitutions. Such conservative substitutions are substitutions in which one amino acid within the following groups (a) – (e) is substituted by another amino acid residue within the same group: (a) small aliphatic, nonpolar or slightly polar residues: Ala, Ser, Thr, Pro and Gly; (b) polar, negatively charged residues and their (uncharged) amides: Asp, Asn, Glu and Gln; (c) polar, positively charged residues: His, Arg and Lys; (d) large aliphatic, nonpolar residues: Met, Leu, Ile, Val and Cys; and (e) aromatic residues: Phe, Tyr and Trp. In one embodiment, conservative substitutions are as follows: Ala into Gly or into Ser; Arg into Lys; Asn into Gln or into His; Asp into Glu; Cys into Ser; Gln into Asn; Glu into Asp; Gly into Ala or into Pro; His into Asn or into Gln; Ile into Leu or into Val; Leu into Ile or into Val; Lys into Arg, into Gln or into Glu; Met into Leu, into Tyr or into Ile; Phe into Met, into Leu or into Tyr; Ser into Thr; Thr into Ser; Trp into Tyr; Tyr into Trp; and / or Phe into Val, into Ile or into Leu. The “aliphatic index”, as used herein, refers to the relative volume occupied by aliphatic side chains (alanine, valine, isoleucine, and leucine)- The aliphatic index of a protein is calculated according to the following formula:Aliphatic index = X(Ala) + a * X(Val) + b * [X(Ile) + X(Leu)] where X(Ala), X(Val), X(Ile), and X(Leu) are mole percent (100 X mole fraction) of alanine, valine, isoleucine, and leucine. The coefficients a and b are the relative volume of valine side chain (a = 2.9) and of Leu / Ile side chains (b = 3.9) to the side chain of alanine (Ikai, A. "Thermostability and aliphatic index of globular proteins." The Journal of Biochemistry 88.6 (1980): 1895-1898). The “GRAVY value” (grand average of hydropathicity value), as used herein, is calculated as the sum of hydropathy value of all the amino acids, divided by the number of residues in the sequence (Kyte, J. "A simple method for displaying the hydropathic character of a protein." J. Mol. Biol.268 (1993): 10558-10563). A “VHH family”, as used in the present specification refers to a group of VHH sequences that have identical lengths (i.e., they have the same number of amino acids within their sequence) and of which the amino acid sequence between position 8 and position 106 (according to Kabat numbering) has an amino acid sequence identity of 89% or more. The terms “epitope” and “antigenic determinant”, which can be used interchangeably, refer to the part of a macromolecule, such as a polypeptide or protein that is recognized by antigen-binding molecules, such as immunoglobulins, conventional antibodies, or immunoglobulin single variable domains, and more particularly by the antigen-binding site of said molecules. Epitopes define the minimum binding site for an immunoglobulin, and thus represent the target of specificity of an immunoglobulin. The part of an antigen-binding molecule (such as an immunoglobulin, a conventional antibody, an immunoglobulin single variable domain) that recognizes the epitope is called a “paratope”. A polypeptide (such as an immunoglobulin, an antibody, an immunoglobulin single variable domain, or generally an antigen binding molecule or a fragment thereof) that can “bind to” or “specifically bind to”, that “has affinity for” and / or that “has specificity for” a certain epitope, antigen or protein (or for at least one part, fragment or epitope thereof) is said to be "against" or “directed against” said epitope, antigen or protein or is a “binding” molecule with respect to such epitope, antigen or protein, or is said to be “anti”-epitope, “anti”-antigen or “anti”-protein (e.g., “anti”- CEACAM5). The terms “specificity”, “binding specifically” or “specific binding” refer to the number of different target molecules, such as antigens, from the same organism to which a particular binding unit, such as an ISVD, can bind with sufficiently high affinity (see below). “Specificity”, “binding specifically” or “specific binding” are used interchangeably herein with “selectivity”, “binding selectively” or “selective binding”. Binding units, such as ISVDs, specifically bind to their designated targets. The specificity / selectivity of a binding unit can be determined based on affinity. The affinity denotes the strength or stability of a molecular interaction. The affinity is commonly given by the KD, or dissociation constant, which has units of mol / liter (or M). The affinity can also be expressed as an association constant, KA, which equals 1 / KD and has units of (mol / liter)-1(or M-1). The affinity is a measure for the binding strength between a moiety and a binding site on the target molecule: the lower the value of the KD, the stronger the binding strength between a target molecule and a targeting moiety. Typically, binding units used in the present technology, such as ISVDs, will bind to their targets with a dissociation constant (KD) of 10-5to 10-12moles / liter or less, 10-7to 10-12moles / liter or less, or 10-8to 10-12moles / liter (i.e., with an association constant (KA) of 105to 1012liter / moles or more, 107to 1012liter / moles or more, or 108to 1012liter / moles). Any KD value greater than 10-4mol / liter (or any KA value lower than 104liters / mol) is generally considered to indicate non-specific binding. The KD for biological interactions, such as the binding of immunoglobulin sequences to an antigen, which are considered specific are typically in the range of 10-5moles / liter (10000 nM or 10µM) to 10-12moles / liter (0.001 nM or 1 pM) or less. Accordingly, specific / selective binding may mean that -using the same measurement method, e.g., SPR- a binding unit (or polypeptide comprising the same) binds to CEACAM5 with a KD value of 10-5to 10-12moles / liter or less and binds to related CEACAMs members with a KD value greater than 10-4moles / liter. An example of a related CEACAMs member is CEACAM1, CEACAM6, CEACAM7 and CEACAM8. Thus, in an embodiment of the present technology, the ISVD binds to (human) CEACAM5 with a KD value of 10-5to 10-12moles / liter or less and binds to CEACAM1, CEACAM6, CEACAM7 or CEACAM8 of the same species with a KD value greater than 10-4moles / liter. Specific binding to a certain target from a certain species does not exclude that the binding unit can also specifically bind to the analogous target from a different species. For example, specific binding to human CEACAM5 does not exclude that the binding unit or a polypeptide comprising the same can also specifically bind to CEACAM5 from cynomolgus monkeys (“cyno”). Specific binding of a binding unit to its designated target can be determined in any suitable manner known per se, including, for example, Scatchard analysis and / or competitive binding assays, such as radioimmunoassays (RIA), enzyme immunoassays (EIA) and sandwich competition assays, and the different variants thereof known per se in the art; as well as the other techniques mentioned further herein. The dissociation constant may be the actual or apparent dissociation constant, as will be clear to the skilled person. Methods for determining the dissociation constant will be clear to the skilled person, and for example include the techniques mentioned herein. In this respect, it will also be clear that it may not be possible to measure dissociation constants of more than 10-4moles / liter or 10-3moles / liter (e.g., of 10-2moles / liter). Optionally, as will also be clear to the skilled person, the (actual or apparent) dissociation constant may be calculated on the basis of the (actual or apparent) association constant (KA), by means of the relationship [KD = 1 / KA]. An amino acid sequence is said to be “cross-reactive” for two different antigens or antigenic determinants (such as e.g., serum albumin from two different species of mammal, such as e.g., human serum albumin and cyno serum albumin, such as e.g., CEACAM5 from different species of mammal, such as e.g., human CEACAM5, cyno CEACAM5 and mouse CEACAM5) if it is specific for (as defined herein) these different antigens or antigenic determinants. The terms “block”, “antagonize”, “compete”, “competing” and “competition” are used interchangeably herein to mean the ability of an immunoglobulin, antibody, immunoglobulin single variable domain, polypeptide or other binding agent to interfere with the binding of another protein, polypeptides, ligand or binding agent to a given target. The extent to which an immunoglobulin, antibody, immunoglobulin single variable domain, polypeptide or other binding agent is able to interfere with the binding of another ligand to the target, and therefore whether it can be said to “block”, can be determined using competition binding assays. Particularly suitable quantitative competitive blocking assays are described in the Examples and include, e.g., a fluorescence-activated cell sorting (FACS) binding assay with CEACAM5 expressed on cells. The extent of blocking can be measured by the (reduced) channel fluorescence. The following generally describes a suitable FACS assay for determining whether an immunoglobulin, antibody, immunoglobulin single variable domain, polypeptide or other binding agent blocks or is capable of blocking. It will be appreciated that the assay can be used with any of the immunoglobulin single variable domains and polypeptides described herein. The FACS instrument (e.g., FACS Canto; Becton Dickinson) is operated in line with the manufacturer's recommendations. To evaluate the “blocking” or “competition” between two binding agents (such as an immunoglobulin single variable domain and a natural ligand or another binding agent) for binding CEACAM5, a FACS competition experiment can be performed using cells (such as, e.g., Flp-In™-293 cells) overexpressing human CEACAM5 and the parental cells as background cell line. Different detection reagents can be used including, e.g., monoclonal ANTI-FLAG® M2 antibody (Sigma- Aldrich, cat# F1804), monoclonal anti-C-myc antibody (Sigma-Aldrich, cat# WH0004609M2), monoclonal ANTI-HIS TAG antibody (Sigma-Aldrich, cat# SAB1305538), each labeled differently. A wide range of fluorophores can be used as labels in flow cytometry (such as, e.g., PE (R- Phycoerythrin), 7-aminoactinomycin D (7-AAD), Acridine Orange, various forms of Alexa Fluor, Allophycocyanin (APC), AmCyan, Aminocoumarin, APC Cy5, APC Cy7, APC-H7, APC / Alexa Fluor 750, AsRed2, Azami-Green, Azurite, B ODIPY FL C5-ceramide, BCECF-AM, Bis-oxonol DiBAC2(3), BODIPY- FL, Calcein, Calcein AM, Caroxy-H2DCFDA, Cascade Blue, Cascade Yellow, Cell Tracker Green, Cerulean, CFSE, Chromomycin A3, CM-H2DCFDA, Cy2, Cy3, Cy3.5, Cy3B, Cy5, Cy5.5, Cy7, CyPet, DAF-FM DAF-FM diacetate, DAPI, DCFH (2'7'Dichorodihydrofluorescein), DHR, Dihydrocalcein AM, Dihydrorhoadamine, Dihydrothidium, DiLC1(5), DiOC6(3), DiOC7(3), dKeima-Red, DRAQ5, Dronpa- Green, various forms of DsRed dTomato, various forms of DyLight, E.coli BioParticles AF488, E2- Crimson, E2-Orange, EBFP2, ECFP, various forms of eFluor, EGFP, EGFP*, Emerald, eqFP650, eqFP670, ER-Tracker Blue-White DPX, Ethidium Bromide, Express2, EYFP, Fc OxyBurst Green, Fc OxyBurst Green 123, FITC, Fluo-3, Fluo-4, Fluorescein, Fura-2, Fura-Red, GFPuv, H2DCFDA, HcRed1, Hoechst Blue (33258), Hoechst Red (33342), Hydroxycoumarin, HyPer, Indo-1, Indo-1 Blue (Low Ca2+), Indo-1 Violet (High Ca2+), iRFP, J-Red, JC-1, JC-9, Katushka (TurboFP635), Katushka2 Kusabira-Orange, LDS 751, Lissamine Rhodamine B, various forms of Live / Dead, Lucifer yellow, Lucifer Yellow CH, Lyso Tracker Blue, Lyso Tracker Green, Lyso Tracker Red, mAmertrine, Marina Blue, mBanana, mCFP, mCherry, mCitrine, Methoxycoumarin, mHoneyDew, Midoriishi-Cyan, Mithramycin, Mito Tracker Deep Red, Mito Tracker Green, Mito Tracker Orange, Mito Tracker Red, MitoFluor Green, mKate (TagFP635), mKate2, mKeima, mKeima-Red, mKO, mKOk, mNeptune, Monochlorobimane, mOrange, mOrange2, mRaspberry, mPlum, mRFP1, mStrawberry, mTangerine, mTarquoise, mTFP1, mTFP1 (Teal), NBD, OxyBurst Green H2DCFDA, OxyBurst Green H2HFF BSA, Pacific Blue, PE (R-Phycoerythrin), PE Cy5, PE Cy5.5, PE Cy7, PE Texas Red, PE-Cy5 conjugates, PE-Cy7 conjugates, PerCP (Peridinin chlorphyll protein), PerCP Cy5.5, PhiYFP, PhiYFP-m, Propidium Iodide (PI), various forms of Qdot, Red 613, RFP Tomato, Rhod-2, S65A, S65C, S65L, S65T, Singlet Oxygen Sensor Green, Sirius, SNARF, Superfolder GFP, SYTOX Blue, SYTOX Green, SYTOX Orange, T-Sapphire, TagBFP, TagCFP, TagGFP, TagRFP, TagRFP657, TagYFP, tdTomato, Texas Red, Thiazole Orange, TMRE, TMRM, Topaz, TOTO-1, TO-PRO-1, TRITC, TRITC TruRed, TurboFP602, TurboFP635, TurboGFP, TurboRFP, TurboYFP, Venus, Vybrant CycleDye Violet, Wild Type GFP, X- Rhodamin, Y66F, Y66H, Y66W, YOYO-1, YPet, ZsGreen1, ZsYellow1, Zymosan A BioParticles AF488 (see more at: http: / / www.thefcn.org / flow-fluorochromes). Fluorophores, or simply “fluors”, are typically attached to the antibody (e.g., the immunoglobulin single variable domain) that recognizes CEACAM5 or to the antibody that is used as detection reagent. Various conjugated antibodies are available, such as (without being limiting) for example antibodies conjugated to Alexa Fluor®, DyLight®, Rhodamine, PE, FITC, and Cy3. Each fluorophore has a characteristic peak excitation and emission wavelength. The combination of labels which can be used will depend on the wavelength of the lamp(s) or laser(s) used to excite the fluorophore and on the detectors available. To evaluate the competition between two test binding agents (termed A and B) for binding to CEACAM5, a dilution series of cold (without any label) binding agent A is added to (e.g., 200000) cells together with the labeled binding agent B*. The concentration of binding agent B* in the test mix should be high enough to readily saturate the binding sites on CEACAM5 expressed on the cells. The concentration of binding agent B* that saturates the binding sites for that binding agent on CEACAM5 expressed on the cells can be determined with a titration series of binding agent B* on the CEACAM5 cells and determination of the EC50 value for binding. In order to work at saturating concentration, binding agent B* can be used at 100x the EC50 concentration. After incubation of the cells with the mixture of binding agent A and binding agent B* and cells wash, read out can be performed on a FACS. First a gate is set on the intact cells as determined from the scatter profile and the total amount of channel fluorescence is recorded. A separate solution of binding agent B* is also prepared. Binding agent B* in this solution should be in the same buffer and at the same concentration as in the test mix (with binding agent A and B*). This separate solution is also added to the cells. After incubation and cells wash, read out can be performed on a FACS. First a gate is set on the intact cells as determined from the scatter profile and the total amount of channel fluorescence is recorded. A reduction of fluorescence for the cells incubated with the mixture of binding agent A and B* compared to the fluorescence for the cells incubated with the separate solution of binding agent B* indicates that binding agent A blocks binding by binding agent B* to CEACAM5 expressed on the cells. A cross-blocking immunoglobulin, antibody, immunoglobulin single variable domain, polypeptide or other binding agent is one which will bind to the CEACAM5 in the above competition FACS such that during the assay and in the presence of the second binding agent the recorded fluorescence is between 80% and 0.1% (e.g., 80% to 4%) of the maximum fluorescence (measured for the separate labelled immunoglobulin, antibody, immunoglobulin single variable domain, polypeptide or other binding agent), specifically between 75% and 0.1% (e.g., 75% to 4%) of the maximum fluorescence, and more specifically between 70% and 0.1% (e.g., 70% to 4%) of maximum fluorescence (as just defined above). The competition between two test binding agents (termed A* and B*) for binding to CEACAM5 can also be evaluated by adding both binding agents, each labeled with a different fluorophore, to the CEACAM5 expressing cells. After incubation and cells wash, read out can be performed on a FACS. A gate is set for each fluorophore and the total amount of channel fluorescence is recorded. Reduction and / or absence of fluorescence of one of the fluorophores indicates blocking by the binding agents for binding to CEACAM5 expressed on the cells. Other methods for determining whether an immunoglobulin, antibody, immunoglobulin single variable domain, polypeptide or other binding agent directed against a target block, is capable of blocking, competitively binds or is competitive as defined herein are described e.g., in Xiao-Chi Jiaet al. (Journal of Immunological Methods 288: 91–98, 2004), Miller et al. (Journal of ImmunologicalMethods 365: 118–125, 2011). As used herein, the term "potency" is a measure of the biological activity of an agent, such as an ISVD or polypeptide. Potency of an agent can be determined by any suitable method known in the art, such as for instance as described in the experimental section. Cell culture-based potency assays are often the preferred format for determining biological activity since they measure the physiological response elicited by the agent and can generate results within a relatively short period of time. Various types of cell-based assays, based on the mechanism of action of the product, can be used, such as e.g., in a FACS assay analysing the binding of the immunoglobulin single variable domains of the present technology to human CEACAM5 expressed on BxPC-3 cells, which is a human pancreatic adenocarcinoma cell line (as further described in the Example section). In contrast, the “efficacy” of an agent, such as an ISVD or polypeptide, measures the maximum strength of the effect itself, at saturating agent concentrations. Efficacy indicates the maximum response achievable from the agent. It refers to the ability of the agent to produce the desired (therapeutic) effect. The efficacy of an agent can be evaluated using in vitro functional assays or in vivo models.5.2 Immunoglobulin single variable domainsThe present technology aims at providing a novel type of drug for treating diseases associated with CEACAM5. The present inventors have surprisingly found that an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO:1 ; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 2 (AbM); and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 230, or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 231; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 232; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 233; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 242; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 256; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 257; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 318; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 319; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 320; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 333; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 335; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 338; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 356; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 357; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 358; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 363; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 364; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 365; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 368; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 369; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 370; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 373; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 374; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 375; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 386; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 387; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 388; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 397; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 398; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 399; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 368; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 379; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 365; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 530; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 531; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 532; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 541; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 542; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 543; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 536; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 537; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 538; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 593; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 578; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 581; or an immunoglobulin single variable domain comprising a CDR1 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 611; a CDR2 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 612; and a CDR3 (AbM numbering) consisting of the amino acid sequence of SEQ ID NO: 610; can bind to CEACAM5 and internalize cells with a high affinity and potency. Moreover, these immunoglobulin single variable domains are highly specific for CEACAM5 and do not bind related CEACAM family members. They are thus a highly specific tool that can be used in the detection, targeting and / or treatment of diseases associated with CEACAM5. The term “immunoglobulin single variable domain” (ISVD), interchangeably used with “single variable domain”, defines immunoglobulin molecules wherein the antigen binding site is present on, and formed by, a single immunoglobulin domain. This sets immunoglobulin single variable domains apart from “conventional” immunoglobulins (e.g., monoclonal antibodies) or their fragments (such as Fab, Fab’, F(ab’)2, scFv, di-scFv), wherein two immunoglobulin domains, in particular two variable domains, interact to form an antigen binding site. Typically, in conventional immunoglobulins, a heavy chain variable domain (VH) and a light chain variable domain (VL) interact to form an antigen binding site. In this case, the complementarity determining regions (CDRs) of both VH and VL will contribute to the antigen binding site, i.e., a total of 6 CDRs will be involved in antigen binding site formation. In view of the above definition, the antigen-binding domain of a conventional 4-chain antibody (such as an IgG, IgM, IgA, IgD or IgE molecule; known in the art) or of a Fab fragment, a F(ab')2 fragment, an Fv fragment such as a disulfide linked Fv or a scFv fragment, or a diabody (all known in the art) derived from such conventional 4-chain antibody, would normally not be regarded as an immunoglobulin single variable domain, as, in these cases, binding to the respective epitope of an antigen would normally not occur by one (single) immunoglobulin domain but by a pair of (associating) immunoglobulin domains such as light and heavy chain variable domains, i.e., by a VH- VL pair of immunoglobulin domains, which jointly bind to an epitope of the respective antigen. In contrast, immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain. The binding site of an immunoglobulin single variable domain is formed by a single VH, a single VHH or single VL domain. As such, the single variable domain may be a light chain variable domain sequence (e.g., a VL- sequence) or a suitable fragment thereof; or a heavy chain variable domain sequence (e.g., a VH- sequence or VHH sequence) or a suitable fragment thereof; as long as it is capable of forming a single antigen binding unit (i.e., a functional antigen binding unit that essentially consists of the single variable domain, such that the single antigen binding domain does not need to interact with another variable domain to form a functional antigen binding unit). An immunoglobulin single variable domain (ISVD) can for example be a heavy-chain ISVD, such as a VHH, including a humanized VHH, a VH, including a camelized VH and a human VH. In one embodiment, it is a VHH, a camelized VH or humanized VHH. Heavy chain ISVDs can be derived from a conventional four-chain antibody or from a heavy chain antibody. For example, the immunoglobulin single variable domain may be a single domain antibody (or an amino acid sequence that is suitable for use as a single domain antibody), a "dAb" or dAb (or an amino acid sequence that is suitable for use as a dAb) or a NANOBODY® ISVD (as defined herein and including but not limited to a VHH); other single variable domains, or any suitable fragment of any one thereof. In particular, the immunoglobulin single variable domain may be a NANOBODY® ISVD (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof. [Note: NANOBODY ® and NANOBODIES® are registered trademarks of Ablynx N.V.] “VHH domains”, also known as VHHs, VHH antibody fragments, have originally been described as the antigen binding immunoglobulin variable domain of “heavy chain antibodies” (i.e., of“antibodies devoid of light chains”; Hamers-Casterman et al. Nature 363: 446-448, 1993). The term“VHH domain” has been chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “VH domains”) and from the light chain variable domains that are present in conventional 4- chain antibodies (which are referred to herein as “VL domains”). For a further description of VHH’s, reference is made to the review article by Muyldermans (Reviews in Molecular Biotechnology 74: 277-302, 2001). The generation of immunoglobulin sequences, such as VHHs, has been described extensively invarious publications, among which WO 94 / 04678, Hamers-Casterman et al.1993 and Muyldermanset al. 2001 (Reviews in Molecular Biotechnology 74: 277-302, 2001). In these methods, camelids are immunized with the target antigen in order to induce an immune response against said target antigen. The repertoire of VHHs obtained from said immunization is further screened for VHHs that bind the target antigen. In these instances, the generation of antibodies requires purified antigen for immunization and / or screening. Antigens can be purified from natural sources, or in the course of recombinant production. Immunization and / or screening for immunoglobulin sequences can be performed using peptide fragments of such antigens. Immunoglobulin sequences of different origin, comprising mouse, rat, rabbit, donkey, human and camelid immunoglobulin sequences can be used in the present technology. Also, fully human, humanized or chimeric sequences can be used. For example, camelid immunoglobulin sequences and humanized camelid immunoglobulin sequences, or camelized domain antibodies, e.g.,camelized dAb as described by Ward et al. (see for example WO 94 / 04678 and Riechmann, FebsLett., 339:285-290, 1994 and Prot. Eng., 9:531-537, 1996) can be used herein. The ISVDs can be fused forming a multivalent and / or multispecific construct (for multivalent and multispecific polypeptides containing one or more VHH domains and their preparation, reference is also madeto Conrath et al. 2001 (J. Biol. Chem., Vol. 276, 10. 7346-7350), as well as to for exampleWO 96 / 34103 and WO 99 / 23221) and immunoglobulin sequences comprising tags or otherfunctional moieties, e.g., toxins, labels, radiochemicals, etc., which are derivable from the immunoglobulin sequences of the present technology. However, it should be noted that the ISVD comprised in the present technology is not limited as to the origin of the ISVD sequence (or of the nucleotide sequence used to express it), nor as to the way that the ISVD sequence or nucleotide sequence is (or has been) generated or obtained. Thus, the ISVD sequences may be naturally occurring sequences (from any suitable species) or synthetic or semi-synthetic sequences. In a specific but non-limiting aspect, the ISVD sequence is a naturally occurring sequence (from any suitable species) or a synthetic or semi-synthetic sequence, including but not limited to “humanized” (as defined herein) immunoglobulin sequences (such as partially or fully humanized camelid, mouse or rabbit immunoglobulin sequences, and in particular partially or fully humanized VHH sequences), “camelized” (as defined herein) immunoglobulin sequences (and in particular camelized VH sequences), as well as ISVDs that have been obtained by techniques such as affinity maturation (for example, starting from synthetic, random or naturally occurring immunoglobulin sequences), CDR grafting, veneering, combining fragments derived from different immunoglobulin sequences, PCR assembly using overlapping primers, and similar techniques for engineering immunoglobulin sequences well known to the skilled person; or any suitable combination of any of the foregoing. Similarly, nucleotide sequences may be naturally occurring nucleotide sequences or synthetic or semi-synthetic sequences, and may for example be sequences that are isolated by PCR from a suitable naturally occurring template (e.g., DNA or RNA isolated from a cell), nucleotide sequences that have been isolated from a library (and in particular, an expression library), nucleotide sequences that have been prepared by introducing mutations into a naturally occurring nucleotide sequence (using any suitable technique known per se, such as mismatch PCR), nucleotide sequence that have been prepared by PCR using overlapping primers, or nucleotide sequences that have been prepared using techniques for DNA synthesis known per se. A “humanized VHH” comprises an amino acid sequence that corresponds to the amino acid sequence of a naturally occurring VHH domain, but that has been “humanized”, i.e., by replacing one or more amino acid residues in the amino acid sequence of said naturally occurring VHH sequence (and in particular in the framework sequences) by one or more of the amino acid residues that occur at the corresponding position(s) in a VH domain from a conventional 4-chain antibody from a human being (e.g., indicated above). This can be performed in a manner known per se, which will be clear to the skilled person, for example on the basis of the prior art (e.g., WO 2008 / 020079). Again, it should be noted that such humanized VHHs can be obtained in any suitable manner known per se and thus are not strictly limited to polypeptides that have been obtained using a polypeptide that comprises a naturally occurring VHH domain as a starting material. A “camelized VH” comprises an amino acid sequence that corresponds to the amino acid sequence of a naturally occurring VH domain, but that has been “camelized”, i.e., by replacing one or more amino acid residues in the amino acid sequence of a naturally occurring VH domain from a conventional 4-chain antibody by one or more of the amino acid residues that occur at the corresponding position(s) in a VHH domain of a (camelid) heavy chain antibody. This can be performed in a manner known per se, which will be clear to the skilled person, for example on the basis of the description in the prior art (e.g., Davies and Riechman (1994 and 1996), supra). Such “camelizing” substitutions are inserted at amino acid positions that form and / or are present at the VH-VL interface, and / or at the so-called Camelidae hallmark residues, as defined herein (see for example WO 94 / 04678 and Davies and Riechmann (1994 and 1996), supra). In one embodiment, the VH sequence that is used as a starting material or starting point for generating or designing the camelized VH is a VH sequence from a mammal, such as the VH sequence of a human being, such as a VH3 sequence. However, it should be noted that such camelized VH can be obtained in any suitable manner known per se and thus are not strictly limited to polypeptides that have been obtained using a polypeptide that comprises a naturally occurring VH domain as a starting material. The structure of an immunoglobulin single variable domain sequence can be considered to be comprised of four framework regions (“FRs”), which are referred to in the art and herein as “Framework region 1” (“FR1”); as “Framework region 2” (“FR2”); as “Framework region 3” (“FR3”); and as “Framework region 4” (“FR4”), respectively; which framework regions are interrupted by three complementary determining regions (“CDRs”), which are referred to in the art and herein as “Complementarity Determining Region 1” (“CDR1”); as “Complementarity Determining Region 2” (“CDR2”); and as “Complementarity Determining Region 3” (“CDR3”), respectively. As further described in paragraph q) on pages 58 and 59 of WO 08 / 020079, the amino acid residuesof an ISVD can be numbered according to the general numbering for VH domains given by Kabat etal. (“Sequence of proteins of immunological interest”, US Public Health Services, NIH Bethesda, MD, Publication No. 91), as applied to VHH domains from Camelids in the article of Riechmann and Muyldermans, 2000 (J. Immunol. Methods 240 (1-2): 185-195; see for example Figure 2 of this publication). It should be noted that – as is well known in the art for VH domains and for VHH domains – the total number of amino acid residues in each of the CDRs may vary and may not correspond to the total number of amino acid residues indicated by the Kabat numbering. That is, one or more positions according to the Kabat numbering may not be occupied in the actual sequence, or the actual sequence may contain more amino acid residues than the number allowed for by the Kabat numbering. This means that, generally, the numbering according to Kabat may or may not correspond to the actual numbering of the amino acid residues in the actual sequence. The total number of amino acid residues in a VH domain and a VHH domain will usually be in the range of from 110 to 120, often between 112 and 115. It should however be noted that smaller and longer sequences may also be suitable for the purposes described herein. In the present application, unless indicated otherwise, CDR sequences were determined according to the AbM numbering as described in Kontermann and Dübel (Eds. 2010, Antibody Engineering, vol 2, Springer Verlag Heidelberg Berlin, Martin, Chapter 3, pp.33-51). According to this method, FR1 of an ISVD comprises the amino acid residues at positions 1-25, CDR1 of an ISVD comprises the amino acid residues at positions 26-35, FR2 of an ISVD comprises the amino acids at positions 36- 49, CDR2 of an ISVD comprises the amino acid residues at positions 50-58, FR3 of an ISVD comprises the amino acid residues at positions 59-94, CDR3 of an ISVD comprises the amino acid residues at positions 95-102, and FR4 of an ISVD comprises the amino acid residues at positions 103-113. Determination of CDR regions may also be done according to different methods. In the CDR determination according to Kabat, FR1 of an ISVD comprises the amino acid residues at positions 1-30, CDR1 of an ISVD comprises the amino acid residues at positions 31-35, FR2 of an ISVD comprises the amino acids at positions 36-49, CDR2 of an ISVD comprises the amino acid residues at positions 50-65, FR3 of an ISVD comprises the amino acid residues at positions 66-94, CDR3 of an ISVD comprises the amino acid residues at positions 95-102, and FR4 of an ISVD comprises the amino acid residues at positions 103-113. The framework sequences are (a suitable combination of) immunoglobulin framework sequences or framework sequences that have been derived from immunoglobulin framework sequences (for example, by humanization or camelization). For example, the framework sequences may be framework sequences derived from a light chain variable domain (e.g., a VL-sequence) and / or from a heavy chain variable domain (e.g., a VH-sequence or VHH sequence). In one particular aspect, the framework sequences are either framework sequences that have been derived from a VHH- sequence (in which said framework sequences may optionally have been partially or fully humanized) or are conventional VH sequences that have been camelized (as defined herein). In particular, the framework sequences present in the ISVD sequence used in the methods described herein may contain one or more of hallmark residues (as defined herein), such that the ISVD sequence is a NANOBODY® ISVD, such as, e.g., a VHH, including a humanized VHH, or camelized VH. Non-limiting examples of (suitable combinations of) such framework sequences will become clear from the further disclosure herein. Generally, NANOBODY® ISVDs (in particular VHH sequences, including (partially) humanized VHH sequences and camelized VH sequences) can be characterized by the presence of one or more “Hallmark residues” (as described herein) in one or more of the framework sequences (again as further described herein). Thus, generally, a NANOBODY® ISVD can be defined as an immunoglobulin sequence with the (general) structure FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4 in which FR1 to FR4 refer to framework regions 1 to 4, respectively, and in which CDR1 to CDR3 refer to the complementarity determining regions 1 to 3, respectively, and in which one or more of the Hallmark residues are as further defined herein. In particular, a NANOBODY® ISVD can be an immunoglobulin sequence with the (general) structure FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4 in which FR1 to FR4 refer to framework regions 1 to 4, respectively, and in which CDR1 to CDR3 refer to the complementarity determining regions 1 to 3, respectively, and in which the framework sequences are as further defined herein. More in particular, a NANOBODY® ISVD can be an immunoglobulin sequence with the (general) structure FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4 in which FR1 to FR4 refer to framework regions 1 to 4, respectively, and in which CDR1 to CDR3 refer to the complementarity determining regions 1 to 3, respectively, and in which: one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from the Hallmark residues mentioned in Table 1 below. Table 1: Hallmark Residues in NANOBODY® ISVDs Position Human VH3 Hallmark Residues11 L, V; predominantly L L, S, V, M, W, F, T, Q, E, A, R, G, K, Y, N, P, I; preferablyL 37 V, I, F; usually V F(1), Y, V, L, A, H, S, I, W, C, N, G, D, T, P, preferably F(1)or Y 44(8) G E(3), Q(3), G(2), D, A, K, R, L, P, S, V, H, T, N, W, M, I;preferably G(2), E(3)or Q(3);most preferably G(2)or Q(3).45(8) L L(2), R(3), P, H, F, G, Q, S, E, T, Y, C, I, D, V; preferably L(2)or R(3)47(8) W, Y F(1), L(1) or W(2) G, I, S, A, V, M, R, Y, E, P, T, C, H, K, Q,N, D; preferably W(2), L(1)or F(1)83 R or K; usually R R, K(5), T, E(5), Q, N, S, I, V, G, M, L, A, D, Y, H;preferably K or R; most preferably K 84 A, T, D; predominantly A P(5), S, H, L, A, V, I, T, F, D, R, Y, N, Q, G, E; preferably P103 W W(4), R(6), G, S, K, A, M, Y, L, F, T, N, V, Q, P(6), E, C;preferably W 104 G G, A, S, T, D, P, N, E, C, L; preferably G108 L, M or T; predominantly L Q, L(7), R, P, E, K, S, T, M, A, H; preferably Q or L(7)Notes: (1) In particular, but not exclusively, in combination with KERE or KQRE at positions 43-46.(2) Usually as GLEW at positions 44-47.(3) Usually as KERE or KQRE at positions 43-46, e.g., as KEREL, KEREF, KQREL, KQREF, KEREG, KQREW or KQREG atpositions 43-47. Alternatively, also sequences such as TERE (for example TEREL), TQRE (for example TQREL), KECE (for example KECEL or KECER), KQCE (for example KQCEL), RERE (for example REREG), RQRE (for example RQREL, RQREF or RQREW), QERE (for example QEREG), QQRE, (for example QQREW, QQREL or QQREF), KGRE (for example KGREG), KDRE (for example KDREV) are possible. Some other possible, but less preferred sequences include for example DECKL and NVCEL. (4) With both GLEW at positions 44-47 and KERE or KQRE at positions 43-46.(5) Often as KP or EP at positions 83-84 of naturally occurring VHH domains.(6) In particular, but not exclusively, in combination with GLEW at positions 44-47.(7) With the proviso that when positions 44-47 are GLEW, position 108 is always Q in (non-humanized) VHHsequences that also contain a W at 103. (8) The GLEW group also contains GLEW-like sequences at positions 44-47, such as for example GVEW, EPEW,GLER, DQEW, DLEW, GIEW, ELEW, GPEW, EWLP, GPER, GLER and ELEW. The present technology relates to ISVDs that specifically bind to CEACAM5. Accordingly, the target molecules for the ISVDs is CEACAM5. Examples are mammalian CEACAM5. Besides human CEACAM5 (SEQ ID NO: 26), the versions from other species are also amenable to the present technology, for example CEACAM5 from mice, rats, rabbits, cats, dogs, goats, sheep, horses, pigs, non-human primates, such as cynomolgus monkeys (also referred to herein as “cyno”), or camelids, such as llama or alpaca. In some embodiments, the ISVDs of the present technology bind to human CEACAM5 (hCEACAM5; SEQ ID NO: 26). In some embodiments, the ISVDs of the present technology bind to human CEACAM5 and cyno CEACAM5 (cCEACAM5; SEQ ID NO: 27). Sequences of human, and cyno CEACAM5 are depicted in Table A-1 (SEQ ID NOs: 26 and 27). The immunoglobulin single variable domains of the present technology show a highly affinity on CEACAM5 (e.g., as measured by SPR) as a (monovalent) single variable domain. In some embodiments, the immunoglobulin single variable domains of the present technology show a high potency for binding CEACAM5 on cells (e.g., as measured in (FACS) binding assay) as a (monovalent) single variable domain. In some embodiments, the immunoglobulin single variable domains of the present technology show a high potency for internalization of CEACAM5 expressing cells (e.g., as measured in internalization assay, for example as described herein) as a (monovalent) single variable domain. In some embodiments, the immunoglobulin single variable domains of the presenttechnology are efficiently produced (e.g., in microbial hosts, such as Pichia, e.g., P. pastoris), evenwhen encompassed with binders to other targets, and have good stability. Because of their small size, (monovalent) immunoglobulin single variable domains are more efficient for the penetration of epithelial tissues. In addition, they are easily combined with other cancer target binders in a multivalent polypeptide when the simultaneous targeting of multiple cancer targets is intended, e.g., as multivalent ISVD construct. The high production yields and better stability demonstrated for immunoglobulin single variable domains makes them ideally suited for subcutaneous administration. In some embodiments, the immunoglobulin single variable domains of the present technology show a highly affinity on CEACAM5 as a (monovalent) single variable domain. The affinity of a molecular interaction between two molecules can be measured via different techniques known per se, such as the well-known surface plasmon resonance (SPR) biosensor technique (see for exampleOber et al. 2001, Intern. Immunology 13: 1551-1559). The term "surface plasmon resonance" or“SPR”, as used herein, refers to an optical phenomenon that allows for the analysis of real-time biospecific interactions by detection of alterations in protein concentrations within a biosensor matrix, where one molecule is immobilized on the biosensor chip and the other molecule is passed over the immobilized molecule under flow conditions yielding kon, koff measurements and hence KD (or KA) values. This can for example be performed using the well-known BIAcore® system (BIAcore International AB, a GE Healthcare company, Uppsala, Sweden and Piscataway, NJ). Forfurther descriptions, see Jonsson et al. 1993 (Ann. Biol. Clin. 51: 19-26), Jonsson et al. 1991(Biotechniques 11: 620-627), Johnsson et al. 1995 (J. Mol. Recognit. 8: 125-131), and Johnnson etal.1991 (Anal. Biochem.198: 268-277). Another well-known biosensor technique to determine affinities of biomolecular interactions is bio-layer interferometry (BLI) (see for example Abdiche et al.2008, Anal. Biochem.377: 209-217). Theterm “bio-layer Interferometry” or “BLI”, as used herein, refers to a label-free optical technique that analyzes the interference pattern of light reflected from two surfaces: an internal reference layer (reference beam) and a layer of immobilized protein on the biosensor tip (signal beam). A change in the number of molecules bound to the tip of the biosensor causes a shift in the interference pattern, reported as a wavelength shift (nm), the magnitude of which is a direct measure of the number of molecules bound to the biosensor tip surface. Since the interactions can be measured in real-time, association and dissociation rates and affinities can be determined. BLI can for example be performed using the well-known Octet® Systems (ForteBio, a division of Pall Life Sciences, Menlo Park, USA). Alternatively, affinities can be measured in Kinetic Exclusion Assay (KinExA) (see for example Drake et al. 2004, Anal. Biochem., 328: 35-43), using the KinExA® platform (Sapidyne Instruments Inc, Boise, USA). The term "KinExA", as used herein, refers to a solution-based method to measure true equilibrium binding affinity and kinetics of unmodified molecules. Equilibrated solutions of an antibody / antigen complex are passed over a column with beads precoated with antigen (or antibody), allowing the free antibody (or antigen) to bind to the coated molecule. Detection of the antibody (or antigen) thus captured is accomplished with a fluorescently labeled protein binding the antibody (or antigen).The GYROLAB® immunoassay system provides a platform for automated bioanalysis and rapidsample turnaround (Fraley et al.2013, Bioanalysis 5: 1765-74).5.2.1 Embodiment 1 -Family 30Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GLTFSTYTMG (SEQ ID NO:1);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GLTFSTYTMG (SEQ ID NO: 1);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences GLTFSTYTMG (SEQ ID NO: 1); and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIIWSGSNTY (SEQ ID NO: 2);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of AIIWSGSNTY (SEQ ID NO: 2); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of AIIWSGSNTY (SEQ ID NO: 2); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein theamino acid residue X is selected from N, A, F, G, I, L, Y or H; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L Y or H. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 1, 2, and / or 230. In one embodiment, the ISVD comprise CDRs (AbM numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 8, 31, 32, 150-159. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 3. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 33. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 249. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 250. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 251. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 252. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 253. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 2 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 254. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315007E07 (SEQ ID NO: 8) and sequence optimized variants thereof in Table A-4 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315007E07 (SEQ ID NO: 8); T028501789 (SEQ ID NO: 31), or T028501789 (E1D) (SEQ ID NO: 32), A031500251 (SEQ ID NO: 150), A031500252 (SEQ ID NO: 151), A031500253 (SEQ ID NO: 152), A031500254 (SEQ ID NO: 153), A031500379 (SEQ ID NO: 154), A031500382 (SEQ ID NO: 155), A031500383 (SEQ ID NO: 156), A031500385 (SEQ ID NO: 157), A031500387 (SEQ ID NO: 158), and A031500394 (SEQ ID NO: 159) (see Table A-2, Table A-4). The SEQ ID NOs for the CDR sequences referred to above are based on the CDR definition according to the AbM definition (see Table A-8). It is noted that the SEQ ID NOs for the CDR sequences defined according to the Kabat definition can likewise be used (see Table A-9). Accordingly, the ISVDs provided by the present technology, specifically binding to CEACAM5 as described above using the AbM definition, can be also described using the Kabat definition. As such in one embodiment, the ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of TYTMG (SEQ ID NO: 17);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of TYTMG (SEQ ID NO: 17); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences of TYTMG (SEQ ID NO: 17); and- CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIIWSGSNTYYADSVKG (SEQ ID NO: 18);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of AIIWSGSNTYYADSVKG (SEQ ID NO: 18); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of AIIWSGSNTYYADSVKG (SEQ ID NO: 18); and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein theamino acid residue X is selected from N, A, F, G, I, L, Y or H; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 17, 18, and / or 230. In one embodiment, the ISVD comprise CDRs (Kabat numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 8, 31, 32, 150-159. In one embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 3. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 33. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 249. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 250. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 251. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 252. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 253. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 17, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 18 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 254. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315007E07 (SEQ ID NO: 8) and sequence optimized variants thereof in Table A-4 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315007E07 (SEQ ID NO: 8); T028501789 (SEQ ID NO: 31), or T028501789 (E1D) (SEQ ID NO: 32), A031500251 (SEQ ID NO: 150), A031500252 (SEQ ID NO: 151), A031500253 (SEQ ID NO: 152), A031500254 (SEQ ID NO: 153), A031500379 (SEQ ID NO: 154), A031500382 (SEQ ID NO: 155), A031500383 (SEQ ID NO: 156), A031500385 (SEQ ID NO: 157), A031500387 ((SEQ ID NO: 158), and A031500394 (SEQ ID NO: 159) (see Table A-2, Table A-4). In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 8, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 8. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 31, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 31. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 32, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 32. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 150, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 150. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 151, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 151. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 152, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 152. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 153, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 153. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 154, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 154. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 155, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 155. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 156, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 156. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 157, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 157. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 158, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 158. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 159, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 159. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 8, 31, 32, 150-159, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8 or other members of the CEACAM family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a dissociation constant (KD) of 10-7to 10-11moles / litre or less, and preferably 10-8to 10-10moles / litre or less and more preferably 1x10-8to 1x10-9moles / litre, even more preferably wherein the ISVD specifically binds to human CEACAM5 with a KD of about 1.34x10-9moles / litre or 1.24x10-9moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 106M-1s-1, such as between 1x105M-1s-1and 5x105M-1s-1, even more preferably of about 3.17x105M-1s-1or 7.16x105M-1s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a koffrate between 10-1s-1(t1 / 2=0.69 s) and 10-6s-1 (providing a near irreversible complex with a t1 / 2 of multiple days), preferably between 10-2s-1and 1x10-6s-1, more preferably between 5x10-3s-1and 1x10-4s-1, such as between 5x10-3s-1and 5x10-4s-1even more preferably of about 4.24x10-3s-1or 8.85x10-4s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a dissociation constant (KD) of 10-7to 10-10moles / litre or less, and preferably 5x10-8to 10-9moles / litre or less and more preferably 5x10-8to 1x10-8moles / litre, even more preferably wherein the ISVD specifically binds to cyno CEACAM5 with a KDof about 1.76x10-8moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 106M-1s-1, such as between 2x105M-1s-1and 1x106M-1s-1, even more preferably of about 2.17x105M-1s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a koff rate between 10-2s-1(t1 / 2=0.69 s) and 10-5s-1(providing a near irreversible complex with a t1 / 2 of multiple days), 10-2s-1and 10-4s-1, more preferably between 5 x 10-3s-1and 5 x 10-4s-1, such as between 5 x 10-3s-1and 1 x 10-3s-1, even more preferably of about 3.81x10-3s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 100-fold lower affinity (KD). In preferred embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to other members of the CEACAMs family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to human and cyno CEACAM1, CEACAM6, CEACAM7 or CEACAM8. A preferred assay for measuring binding and internalization of the ISVD (or polypeptide comprising the ISVD) to CEACAM5 exposed on a cell surface is a FACS assay. For instance, the ISVDs or polypeptides of the present invention can be applied to cancer cell lines overexpressing CEACAM5, such as a BxPC-3 cell line, which is a human pancreatic adenocarcinoma cell line. VHH bound to human CEACAM5 can be detected with a fluorophore- labelled anti-VHH antibody and the cells can be analyzed with a flow cytometer to evaluate the binding properties of ISVDs or polypeptides of the present invention. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5. For example, in a FACS binding assay with a BxPC-3 cell line expressing human CEACAM5, the immunoglobulin single variable domains of the present technology may have EC50 values of 10-7M or lower, more preferably of 10-8M or lower, or even of 10-9M or lower. For example, in such FACS assay, the immunoglobulin single variable domains of the present technology may have EC50 values between 10-11M and 10-8M, such as between 10-10M and 10-8M, between 5x10-9M and 10-8M or between 10-9M and 10-8M. In some embodiments, the immunoglobulin single variable domains of the present technology has an CEACAM5-mediated internalization potency (EC50 value) of 10-7M or lower, more preferably of 5x10-8M or lower, or even of 10-8M or lower, such as between 10-7M and 10-10M, between 10-7M and 10-9M, between 5x10-8M and 10-9M or between 5x10-8M and 10-8M, for example, as measured in a FACS internalization assay on BxPC-3 cells expressing human CEACAM5.5.2.2 Embodiment 2 -Family 4Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GX1TFSX2YAX3G (SEQ ID NO: 231), wherein the aminoacid residue X1 is selected from R or H, the amino acid residue X2 is selected from E or D and the amino acid residue X3 is selected from L or M;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GX1TFSX2YAX3G (SEQ ID NO: 231), wherein the amino acid residueX1 is selected from R or H, the amino acid residue X2 is selected from E or D and the amino acid residue X3 is selected from L or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences GX1TFSX2YAX3G (SEQ ID NO: 231), wherein the amino acid residue X1is selected from R or H, the amino acid residue X2is selected from E or D and the amino acid residue X3is selected from L or M; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AINWGGXWTY (SEQ ID NO: 232), wherein the aminoacid residue X is selected from T, G or S; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of AINWGGXWTY (SEQ ID NO: 232), wherein the amino acid residueX is selected from T, G or S; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of AINWGGXWTY (SEQ ID NO: 232), wherein the amino acid residueX is selected from T, G or S); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein theamino acid residue X1is selected from S, P or L, the amino acid residue X2is selected from N or S, the amino acid residue X3 is selected from P or A; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein the amino acid residue X1is selected from S, P or L, the amino acid residue X2is selected from N or S, the amino acid residue X3is selected from P or A; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein the amino acid residue X1is selected from S, P or L, the amino acid residue X2is selected from N or S, the amino acid residue X3 is selected from P or A. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 231, 232, and / or 233. In one embodiment, the ISVD comprise CDRs (AbM numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 16, 39, 40, 120, 121, 135-149. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 9, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 10 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 11. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 234, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 235 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 236. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 234, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 238 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 239. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315024B02 (SEQ ID NO: 16) and sequence optimized variants thereof in Table A-3 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315024B02 (SEQ ID NO: 16); T028501817 (SEQ ID NO: 39), or T028501817(E1D) (SEQ ID NO: 40), A031500086 (SEQ ID NO: 135), A031500087 (SEQ ID NO: 136), A031500088 (SEQ ID NO: 137), A031500089 (SEQ ID NO: 138), A031500090 (SEQ ID NO: 139), A031500091 (SEQ ID NO: 140), A031500092 (SEQ ID NO: 141), A031500093 (SEQ ID NO: 142), A031500094 (SEQ ID NO: 143), A031500095 (SEQ ID NO: 144), A031500096 (SEQ ID NO: 145, A031500097 (SEQ ID NO: 146), A031500098 (SEQ ID NO: 147), and A031500100 (SEQ ID NO: 148) and A031500101 (SEQ ID NO: 149) (see Table A-2, Table A-3). In other embodiments, the ISVDcomprises or consists of the full amino acid sequence of A0315001C02 (SEQ ID NO.: 120) orA0315026D05 (SEQ ID NO.: 121), see Table A-2. The SEQ ID NOs for the CDR sequences referred to above are based on the CDR definition according to the AbM definition (see Table A-8). It is noted that the SEQ ID NOs for the CDR sequences defined according to the Kabat definition can likewise be used (see Table A-9). Accordingly, the ISVDs provided by the present technology, specifically binding to CEACAM5 as described above using the AbM definition, can be also described using the Kabat definition. As such in one embodiment, the ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of X1YAX2G (SEQ ID NO: 240), wherein the amino acidresidue X1is selected from E or D, and the amino acid residue X2is selected from L or M; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of X1YAX2G (SEQ ID NO: 240), wherein the amino acid residue X1 is selected from E or D, and the amino acid residue X2 is selected from L or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences of X1YAX2G (SEQ ID NO: 240), wherein the amino acid residue X1 is selected from E or D, and the amino acid residue X2is selected from L or M; and -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AINWGGX1WTYYAX2SVX3G (SEQ ID NO: 241); wherein theamino acid residue X1 is selected from G, S or T, and the amino acid residue X2 is selected from H or D, and the amino acid residue X3 is selected from Q or K; b) amino acid sequences that have at least 80% amino acid identity with the amino acidsequence of AINWGGX1WTYYAX2SVX3G (SEQ ID NO: 241); wherein the amino acid residue X1is selected from G, S or T, and the amino acid residue X2is selected from H or D, and the amino acid residue X3 is selected from Q or K; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acidsequence of AINWGGX1WTYYAX2SVX3QG (SEQ ID NO: 241); wherein the amino acid residue X1 is selected from G, S or T, and the amino acid residue X2 is selected from H or D, and the amino acid residue X3 is selected from Q or K; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein theamino acid residue X1 is selected from S, P or L, the amino acid residue X2 is selected from N or S, the amino acid residue X3 is selected from P or A; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein the amino acid residue X1is selected from S, P or L, the amino acid residue X2is selected from N or S, the amino acid residue X3 is selected from P or A; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SX1DYAGGX2PTGYX3Y (SEQ ID NO: 233), wherein the amino acid residue X1is selected from S, P or L, the amino acid residue X2is selected from N or S, the amino acid residue X3is selected from P or A. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 240, 241, and / or 233. In one embodiment, the ISVD comprise CDRs (Kabat numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 16, 39, 40, 120, 121, 135-149. In one embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 21, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 22 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 11. In one embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 21, a CDR2 (Kabat numbering) that is the amino acid sequence of (AINWGGGWTYYADSVKG) SEQ ID NO: 43 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 11. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 243, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 244 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 236. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 243, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 245 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 246. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315024B02 (SEQ ID NO: 16) and sequence optimized variants thereof in Table A-3 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315024B02 (SEQ ID NO: 16); T028501817 (SEQ ID NO: 39), or T028501817(E1D) (SEQ ID NO: 40), A031500086 (SEQ ID NO: 135), A031500087 (SEQ ID NO: 136), A031500088 (SEQ ID NO: 137), A031500089 (SEQ ID NO: 138), A031500090 (SEQ ID NO: 139), A031500091 (SEQ ID NO: 140), A031500092 (SEQ ID NO: 141), A031500093 (SEQ ID NO: 142), A031500094 (SEQ ID NO: 143), A031500095 (SEQ ID NO: 144), A031500096 (SEQ ID NO: 145), A031500097 (SEQ ID NO: 146), A031500098 (SEQ ID NO: 147), and A031500100 (SEQ ID NO: 148) and A031500101 (SEQ ID NO: 149) (see Table A-2, Table A-3). In another embodiment, theISVD comprises or consists of the full amino acid sequence of A0315001C02 (SEQ ID NO: 120) orA0315026D05 (SEQ ID NO: 121), Table A-2. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 16, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 16. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 39, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 39. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 40, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 40. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 120, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 120. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 121, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 121. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 135, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 135. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 136, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 136. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 137, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 137. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 138, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 138. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 139, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 139. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 140, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 140. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 141, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 141. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 142, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 142. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 143, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 143. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 144, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 144. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 145, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 145. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 146, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 146. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 147, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 147. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 148, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 148. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 149, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 149. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, wherein the binding affinity is measured using the same method, such as, e.g, SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135- 149, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 16, 39, 40, 120, 121, 135-149, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with dissociation constant (KD) of 10-7to 10-10moles / litre or less, and preferably 5x10-8to 10-9moles / litre or less and more preferably 5x10-8to 5x10-9moles / litre, even more preferably wherein the ISVD specifically binds to human CEACAM5 with a KDof about 1.06x10-8moles / litre, 4,86x10-9moles / litre or 8.9x10-9moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 106M-1s-1, such as between 1x105M-1s-1and 5x105M-1s-1, even more preferably of about 1.2x105M-1s-1, 1.6x105M-1s-1, 1.98x105M-1s, or 2.38x105M-1s , as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a koff rate between 10-2s-1(t1 / 2=0.69 s) and 10-6s-1(providing a near irreversible complex with a t1 / 2 of multiple days), preferably between 5x10-3s-1and 5x10-5s-1, more preferably between 5x10-3s-1and 5x10-4s-1, such as between 5x10-3s-1and 1x10-4s-1, even more preferably of about 1.08x10-3s-1, 1.7x10-3s-1, 9.61x10-4s-1or 2.12x10-3s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a dissociation constant (KD) of 10-7to 10-11moles / litre or less, and preferably 10-8to 10-10moles / litre or less and more preferably 5x10-9to 10-9moles / litre, even more preferably wherein the ISVD specifically binds to cyno CEACAM5 with a KD of about 6.94x10-9moles / litre, 2.28x10-9moles / litre or 4.86x10-9moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 106M-1s-1, such as between 2x105M-1s-1and 1x106M-1s-1, even more preferably of about 5.9x105M-1s-1, 9.94x105M-1s-1, or 8.62x105M-1s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a koff rate between 10-2s-1(t1 / 2=0.69 s) and 10-5s-1(providing a near irreversible complex with a t1 / 2 of multiple days), 10-2s-1and 10-4s-1, more preferably between 5 x 10-3s-1and 5 x 10-4s-1, such as between 5x10-3s-1and 1x10-3s-1, even more preferably of about 4,09x10-3s-1, 2.26x10-3s-1, or 2.50x10-3s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 100-fold lower affinity (KD). In preferred embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to other members of the CEACAMs family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to human and cyno CEACAM1, CEACAM6, CEACAM7 or CEACAM8. A preferred assay for measuring binding and internalization of the ISVD (or polypeptide comprising the ISVD) to CEACAM5 exposed on a cell surface is a FACS assay. For instance, the ISVDs or polypeptides of the present invention can be applied to cancer cell lines overexpressing CEACAM5, such as a BxPC-3 cell line, which is a human pancreatic adenocarcinoma cell line. VHH bound to human CEACAM5 can be detected with a fluorophore- labelled anti-VHH antibody and the cells can be analyzed with a flow cytometer to evaluate the binding properties of ISVDs or polypeptides of the present invention. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5. For example, in a FACS assay analysing the binding of the immunoglobulin single variable domains of the present technology to human CEACAM5 expressed on BxPC-3 cells, the immunoglobulin single variable domains of the present technology may have EC50 values of 10-7M or lower, more preferably of 5x10-8M or lower, or even of 10-8M or lower. For example, in such FACS assay, the immunoglobulin single variable domains of the present technology may have EC50 values between 10-11M and 10-7M, such as between 10-10M and 10-7M, between 10-9M and 5x10-8M or between 5x10-9M and 5x10-8M. In some embodiments, the immunoglobulin single variable domains of the present technology has an CEACAM5-mediated internalization potency (EC50 value) of 5x10-7M or lower, more preferably of 10-7M or lower, or even of 5x10-8M or lower, such as between 10-7M and 10-10M, between 10-7M and 10-9M, between 8x10-8M and 10-9M or between 8x10-8M and 10-8M, for example, as measured in a FACS internalization assay on BxPC-3 cells expressing human CEACAM5.5.2.3 Embodiment 3 -Family 1Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GRTFXSYDMG (SEQ ID NO: 242), wherein the amino acidresidue X is selected from N, E, G, P, S or T; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GRTFXSYDMG (SEQ ID NO: 242), wherein the amino acid residue X isselected from N, E, G, P, S or T; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GRTFXSYDMG (SEQ ID NO: 242), wherein the amino acid residue X isselected from N, E, G, P, S or T; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIRWSAGSTV (SEQ ID NO: 256);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence AIRWSAGSTV (SEQ ID NO: 256);c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence AIRWSAGSTV (SEQ ID NO: 256); and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence VRPSFRPLSTYWKDYDN (SEQ ID NO: 257);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence VRPSFRPLSTYWKDYDN (SEQ ID NO: 257); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence VRPSFRPLSTYWKDYDN (SEQ ID NO: 257). Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 242, 256, and / or 257. In one embodiment, the ISVD comprise CDRs (AbM numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 114, 175-208. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 255, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 256 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 257. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 284, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 256 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 257. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 285, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 256 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 257. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 286, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 256 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 257. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 287, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 256 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 257. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 288, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 256 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 257. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315001D07 (SEQ ID NO: 114) and sequence optimized variants thereof in Table A-7 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A031500014 (SEQ ID NO: 175), A031500015 (SEQ ID NO: 176), A031500016 (SEQ ID NO: 177), A031500017 (SEQ ID NO: 178), A031500018 (SEQ ID NO: 179), A031500019 (SEQ ID NO: 180), A031500020 (SEQ ID NO: 181), A031500021 (SEQ ID NO: 182), A031500022 (SEQ ID NO: 183), A031500023 (SEQ ID NO: 184), A031500024 (SEQ ID NO: 185), A031500025 (SEQ ID NO: 186), A031500026 (SEQ ID NO: 187), A031500027 (SEQ ID NO: 188), A031500028 (SEQ ID NO: 189), A031500029 (SEQ ID NO: 190), A031500030 (SEQ ID NO: 191), A031500031 (SEQ ID NO: 192), A031500032 (SEQ ID NO: 193), A031500033 (SEQ ID NO: 194), A031500034 (SEQ ID NO: 195), A031500035 (SEQ ID NO: 196), A031500368 (SEQ ID NO: 197), A031500369 (SEQ ID NO: 198), A031500370 (SEQ ID NO: 199), A031500345 (SEQ ID NO: 200), A031500346 (SEQ ID NO: 201), A031500347 (SEQ ID NO: 202), A031500348 (SEQ ID NO: 203), A031500406 (SEQ ID NO: 204), A031500407 (SEQ ID NO: 205), A031500408 (SEQ ID NO: 206), A031500409 (SEQ ID NO: 207), or A031500410 (SEQ ID NO: 208), (see Table A-7). In another embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315001D07 (SEQ ID NO: 114) (see Table A-2 and Table A-7). The SEQ ID NOs for the CDR sequences referred to above are based on the CDR definition according to the AbM definition (see Table A-8). It is noted that the SEQ ID NOs for the CDR sequences defined according to the Kabat definition can likewise be used (see Table A-9). Accordingly, the ISVDs provided by the present technology, specifically binding to CEACAM5 as described above using the AbM definition, can be also described using the Kabat definition. As such in one embodiment, the ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SYDMG (SEQ ID NO: 289);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SYDMG (SEQ ID NO: 289); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences of SYDMG (SEQ ID NO: 289); and -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of AIRWSAGSTVYX1X2SVKG (SEQ ID NO: 290); whereinthe amino acid residue X1is selected from G or A and wherein the amino acidresidue X2 is selected from N or D; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of AIRWSAGSTVYX1X2SVKG (SEQ ID NO: 290); wherein the amino acidresidue X1is selected from G or A and wherein the amino acid residue X2 is selectedfrom N or D; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of AIRWSAGSTVYX1X2SVKG (SEQ ID NO: 290); wherein the amino acidresidue X1is selected from G or A and wherein the amino acid residue X2 is selectedfrom N or D; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of VRPSFRPLSTYWKDYDN (SEQ ID NO: 257);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of VRPSFRPLSTYWKDYDN (SEQ ID NO: 257); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of VRPSFRPLSTYWKDYDN (SEQ ID NO: 257). Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 289, 290, and / or 257. In one embodiment, the ISVD comprise CDRs (Kabat numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 114, 175-208. In one embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 289, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 291 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 257. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 289, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 292 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 257. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 289, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 293 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 257. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 289, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 294 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 257. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315001D07 (SEQ ID NO: 114) and sequence optimized variants thereof in Table A-7 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A031500014 (SEQ ID NO: 175), A031500015 (SEQ ID NO: 176), A031500016 (SEQ ID NO: 177), A031500017 (SEQ ID NO: 178), A031500018 (SEQ ID NO: 179), A031500019 (SEQ ID NO: 180), A031500020 (SEQ ID NO: 181), A031500021 (SEQ ID NO: 182), A031500022 (SEQ ID NO: 183), A031500023 (SEQ ID NO: 184), A031500024 (SEQ ID NO: 185), A031500025 (SEQ ID NO: 186), A031500026 (SEQ ID NO: 187), A031500027 (SEQ ID NO: 188), A031500028 (SEQ ID NO: 189), A031500029 (SEQ ID NO: 190), A031500030 (SEQ ID NO: 191), A031500031 (SEQ ID NO: 192), A031500032 (SEQ ID NO: 193), A031500033 (SEQ ID NO: 194), A031500034 (SEQ ID NO: 195), A031500035 (SEQ ID NO: 196), A031500368 (SEQ ID NO: 197), A031500369 (SEQ ID NO: 198), A031500370 (SEQ ID NO: 199), A031500345 (SEQ ID NO: 200), A031500346 (SEQ ID NO: 201), A031500347 (SEQ ID NO: 202), A031500348 (SEQ ID NO: 203), A031500406 (SEQ ID NO: 204), A031500407 (SEQ ID NO: 205), A031500408 (SEQ ID NO: 206), A031500409 (SEQ ID NO: 207), or A031500410 (SEQ ID NO: 208), (see Table A-7). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315001D07 (SEQ ID NO: 114) (see Table A-2 and Table A-7). In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 114, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 114. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequenceidentity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 175,wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding toCEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 175.In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequenceidentity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 176,wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding toCEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 176.In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 177, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 177. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 178, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 178. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 179, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 179. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 180, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 180. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 181, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 181. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 182, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 182. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 183, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 183. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 184, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 184. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 185, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 185. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 186, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 186. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 187, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 187. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 188, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 188. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 189, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 189. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 190, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 190. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 191, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 191. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 192, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 192. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 193, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 193. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 194, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 194. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 195, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 195. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 196, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 196. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 197, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 197. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 198, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 198. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 199, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 199. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 200, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 200. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 201, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 201. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 202, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 202. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 203, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 203. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 204, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 204. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 205, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 205. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 206, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 206. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 207, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 207. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 208, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 208. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 114, 175-208, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 114, 175-208, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 114, 175-208, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 114, 175-208, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8, or other members of the CEACAM family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 114, 175-208, the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 114, 175-208, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 114, 175-208, the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 114, 175-208, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 114, 175-208, the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 114, 175-208, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 114, 175-208, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8 or other members of the CEACAM family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a dissociation constant (KD) of 10-7to 10-11moles / litre or less, and preferably 10-7to 10-9moles / litre or less and more preferably 5x10-7to 1x10-8moles / litre, even more preferably wherein the ISVD specifically binds to human CEACAM5 with a KD of about 1.87x10-8moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 106M-1s-1, such as between 1x105M-1s-1and 5x105M-1s-1, even more preferably of about 3.96x105M-1s-1,as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a koffrate between 10-2s-1(t1 / 2=0.69 s) and 10-6s-1(providing a near irreversible complex with a t1 / 2 of multiple days), preferably between 10-2s-1and 1x10-5s-1, more preferably between 1x10-2s-1and 1x10-3s-1, such as between 1x10-2s-1and 5x10-3s-1even more preferably of about 7.41x10-3s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a dissociation constant (KD) of 10-6to 10-10moles / litre or less, and preferably 5x10-7to 10-9moles / litre or less and more preferably 5x10-7to 1x10-8moles / litre, even more preferably wherein the ISVD specifically binds to cyno CEACAM5 with a KDof about 7.92x10-7moles / litre or 1.73x10-7moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a koff rate between 10-1s-1(t1 / 2=0.69 s) and 10-5s-1(providing a near irreversible complex with a t1 / 2 of multiple days), 5x10-1s-1and 10-4s-1, more preferably between 1.x 10-2s-1and 1 x 10-3s-1, such as between 1.83 x 10-2s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 100-fold lower affinity (KD). In preferred embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to other members of the CEACAMs family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to human and cyno CEACAM1, CEACAM6, CEACAM7 or CEACAM8. A preferred assay for measuring binding and internalization of the ISVD (or polypeptide comprising the ISVD) to CEACAM5 exposed on a cell surface is a FACS assay. For instance, the ISVDs or polypeptides of the present invention can be applied to cancer cell lines overexpressing CEACAM5, such as a BxPC-3 cell line, which is a human pancreatic adenocarcinoma cell line. VHH bound to human CEACAM5 can be detected with a fluorophore- labelled anti-VHH antibody and the cells can be analyzed with a flow cytometer to evaluate the binding properties of ISVDs or polypeptides of the present invention.5.2.4 Embodiment 4 -Family 2Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), that interacts with one or more amino acids of the CEACAM5 protein selected from K324, P325, F326, I327, T328, S329, N330, N331, S332, N333, D339, E346, S404, D405, P406, V407, I408, N410, L412, P443, P444, and A483. In another specific embodiments, the ISVD interacts with an epitope on CEACAM5 that comprises at least three amino acids selected from K324, P325, F326, I327, T328, S329, N330, N331, S332, N333, D339, E346, S404, D405, P406, V407, I408, N410, L412, P443, P444, and A483. In another specific embodiments, the ISVD interacts with an epitope on CEACAM5 that comprises at least five amino acids selected from K324, P325, F326, I327, T328, S329, N330, N331, S332, N333, D339, E346, S404, D405, P406, V407, I408, N410, L412, P443, P444, and A483. In another specific embodiments, the ISVD interacts with an epitope on CEACAM5 that comprises at least eight amino acids selected from K324, P325, F326, I327, T328, S329, N330, N331, S332, N333, D339, E346, S404, D405, P406, V407, I408, N410, L412, P443, P444, and A483. In another specific embodiments, the ISVD interacts with an epitope on CEACAM5 that comprises at least 10 amino acids selected from K324, P325, F326, I327, T328, S329, N330, N331, S332, N333, D339, E346, S404, D405, P406, V407, I408, N410, L412, P443, P444, and A483. In another specific embodiments, the ISVD interacts with an epitope on CEACAM5 that comprises following amino acids: K324, S329, N330, N331, S332, N333, E346, and D405. In another specific embodiments, the epitope on CEACAM5 that is specifically bound by the ISVDs of the present technology comprises following amino acids: K324, P325, F326, I327, T328, S329, N330, N331, S332, N333, D339, E346, S404, D405, P406, V407, I408, N410, L412, P443, P444, and A483. The interacting amino acids preferably have a distance of <3.8Å, wherein the distance between the amino acids is measured e.g., in Cryogenic-electron microscopy (cryo-EM). The ISVDs specifically binding to this epitope on CEACAM5 form an interaction site (paratope) on CEACAM5 only with the CDR2 and CDR3. As such, only CDR2 and CDR3 of the ISVD participate in the interaction with the CEACAM5 protein. Only CDR2 and CDR3 of the ISVD form part of the paratope (the site with which the ISVD interacts with the CEACAM5 molecule) of the ISVD. In someembodiments, the amino acids that form part of this interaction sites are selected from S52, W52a,R53, S54, I56, and V58 (Kabat numbering) in CDR2. In some embodiments, the amino acids thatform part of this interaction sites are selected from Q95, E96, F97, G98, A99, I100, S100a, Y100b, N100c, K100e, G100f, Y100g, F101, Y102 (Kabat numbering) in the CDR3. In some embodiment, the amino acids that form part of this interaction sites are selected from S52, W52a, R53, S54, I56, and V58 (Kabat numbering) in CDR2 and from Q95, E96, F97, G98, A99, I100, S100a, Y100b, N100c, K100e, G100f, Y100g, F101, and Y102 (Kabat numbering) in the CDR3. In some embodiments, the amino acids that form part of this interaction sites are S52, W52a, R53, S54, I56, and V58 (Kabat numbering) in CDR2. In some embodiments, the amino acids that form part of this interaction sites are Q95, F97, I100, S100a, N100c, and K100e (Kabat numbering) in the CDR3. In some embodiments, the amino acids that form part of this interaction sites are Q95, E96, F97, G98, A99, I100, S100a, Y100b, N100c, K100e, G100f, Y100g, F101, and Y102 (Kabat numbering) in the CDR3. In some embodiments, the amino acids that form part of this interaction sites are S52, W52a, R53, S54, I56, and V58 (Kabat numbering) in CDR2 and G98, A99, I100, S100a, Y100b, N100c, K100e, G100f, Y100g, F101, and Y102 (Kabat numbering) in the CDR3. In some embodiments, the amino acids that form part of this interaction sites are Q95, F97, I100, S100a, N100c, or K100e (Kabat numbering) in the CDR3, wherein Q95 forms an interaction site (<3.8Å distance) with N333 in the CEACAM5 epitope, wherein F97 forms an interaction site (<3.8Å distance) with I408 in the CEACAM5 epitope, wherein I100 forms an interaction site (<3.8Å distance) with I327 in the CEACAM epitope, wherein I100 forms an interaction site (<3.8Å distance) with S329 in the CEACAM5 epitope, wherein S100a forms an interaction site (<3.8Å distance) with S329 in the CEACAM5 epitope, wherein N100c forms an interaction site (<3.8Å distance) with N330 in the CEACAM5 epitope and / or wherein K100e forms an interaction site (<3.8Å distance) with S332 in the CEACAM 5 epitope. In some embodiments, the amino acids that form part of this interaction sites are Q95, F97, I100, S100a, N100c, and K100e (Kabat numbering) in the CDR3, wherein Q95 forms an interaction site (<3.8Å distance) with N333 in the CEACAM5 epitope, wherein F97 forms an interaction site (<3.8Å distance) with I408 in the CEACAM5 epitope, wherein I100 forms an interaction site (<3.8Å distance) with I327 in the CEACAM epitope, wherein I100 forms an interaction site (<3.8Å distance) with S329 in the CEACAM5 epitope, wherein S100a forms an interaction site (<3.8Å distance) with S329 in the CEACAM5 epitope, wherein N100c forms an interaction site (<3.8Å distance) with N330 in the CEACAM5 epitope and / or wherein K100e forms an interaction site (<3.8Å distance) with S332 in the CEACAM 5 epitope (wherein the distance between the amino acids is measured e.g., in Cryogenic-electron microscopy (cryo-EM)). The ISVDs specifically binding to this epitope on CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO:319); wherein the amino acid residue X1,X2, X2or X4is any amino acid independently chosen, preferably wherein the amino acid residue X4is I, and / or -CDR3 (AbM numbering) consists of an amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ IDNO: 320); wherein the amino acid residue X1, X2, X3,X4and X5is any amino acid independently chosen, preferably wherein the amino acid residue X1 is E, wherein the amino acid residue X2 is F, wherein the amino acid residue X4 is K and the amino acid residue X5 is Y. The ISVDs specifically binding to this epitope on CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO:319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acidresidue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G orE and wherein the amino acid residue X4 is selected from T or I, preferably wherein theamino acid residue X4is I; and -CDR3 (AbM numbering) consists of an amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ IDNO: 320); wherein the amino acid residue X1 is selected from Q or E, wherein the aminoacid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected fromT or R and wherein the amino acid residue X4 is selected from N or K, and wherein theamino acid residue X5is selected from F or Y, preferably wherein the amino acid residue X1 is E, the amino acid residue X2 is F, the amino acid residue X4 is K and the amino acid residue X5 is Y. In a preferred embodiment, the ISVDs specifically binding to this epitope on CEACAM5 further comprises a CDR1 (AbM Numbering): a) having a length of 10 amino acids;b) having an aliphatic index of 20.00;c) having a grand average of hydropathicity (GRAVY) of 0.400, -0.010, preferably -0.010;d) comprising no or only one positively-charged amino acid residue;e) comprising 40% hydrophobic, 0% or 10% basic and 50 or 60% neutral amino acids,such as comprising 40% hydrophobic, and 60% neutral amino acids; or comprising 40% hydrophobic, 10% basic and 50% neutral amino acids; f) consisting of a polar neutral amino acid, a basic or polar neutral amino acid, twohydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; such as consisting of two polar neutral amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; or consisting of a polar neutral amino acid, a basic amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; and / org) comprising at least one, preferably all of the amino acids G, A, F, S, Y, A, M, and / oroptionally the amino acid R. In some embodiments, the ISVDs specifically binding to this epitope on CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO:319); wherein the amino acid residue X1is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4 is selected from T or I, preferably wherein the amino acid residue X4 is I; and -CDR3 (AbM numbering) consists of an amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ IDNO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y, preferably wherein the amino acid residue X1 is E, the amino acid residue X2 is F, the amino acid residue X4 is K and the amino acid residue X5 is Y, and -CDR1 (AbM Numbering):a) having a length of 10 amino acids;b) having an aliphatic index of 20.00;c) having a grand average of hydropathicity (GRAVY) of 0.400, -0.010, preferably -0.010;d) comprising no or one positively-charged amino acid residue;e) comprising 40% hydrophobic, 0% or 10% basic and 50 or 60% neutral amino acids,such as comprising 40% hydrophobic, and 60% neutral amino acids; or comprising 40% hydrophobic, 10% basic and 50% neutral amino acids; f) consisting of a polar neutral amino acid, a basic or polar neutral amino acid, twohydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; such as consisting of two polar neutral amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; or consisting of a polar neutral amino acid, a basic amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; and / org) comprising at least one, preferably all of the amino acids G, A, F, S, Y, A, M, and / oroptionally the amino acid R. In some embodiments, the ISVDs specifically binding to the above specific epitope on CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acidresidue X is selected from R or G; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acid residue X is selected from R or G; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acid residue X is selected from R or G; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the aminoacid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3is selected from G or E and wherein the amino acid residue X4is selected from T or I; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4is selected from T or I; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence the amino acid X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3is selected from G or E and wherein the amino acid residue X4 is selected from T or I; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y. It should be noted, however, that the ISVDs specifically binding to CEACAM5 may not necessarily be limited to those binding to the above-specified epitope. Hence, specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the aminoacid residue X1is selected from A or T, wherein the amino acid residue X2is selected from L or I, wherein the amino acid residue X3is selected from G or E and wherein the amino acid residue X4is selected from T or I; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4 is selected from T or I;c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence the amino acid X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4 is selected from T or I; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5is selected from F or Y; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y. The following embodiments, thus, apply to any of the ISVDs described above, i.e., the ISVDs binding specifically to CEACAM5 and which are not necessarily limited to binding to the above specific epitope on CEACAM5 and to ISVDs specifically binding to the above-specified epitope on CEACAM5. In a preferred embodiment, the ISVDs specifically binding to CEACAM5 further comprises a CDR1 (AbM Numbering): a) having a length of 10 amino acids;b) having an aliphatic index of 20.00;c) having a grand average of hydropathicity (GRAVY) of 0.400, -0.010, preferably -0.010;d) comprising no or one positively-charged amino acid residue;e) comprising 40% hydrophobic, 0% or 10% basic and 50 or 60% neutral amino acids,such as comprising 40% hydrophobic, and 60% neutral amino acids; or comprising 40% hydrophobic, 10% basic and 50% neutral amino acids; f) consisting of a polar neutral amino acid, a basic or polar neutral amino acid, twohydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; such as consisting of two polar neutral amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; or consisting of a polar neutral amino acid, a basic amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; and / or g) comprising at least one, preferably all of the amino acids G, A, F, S, Y, A, M, and / orand / or optionally the amino acid R. In some embodiments, the ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the aminoacid residue X1is selected from A or T, wherein the amino acid residue X2is selected from L or I, wherein the amino acid residue X3is selected from G or E and wherein the amino acid residue X4is selected from T or I; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3is selected from G or E and wherein the amino acid residue X4is selected from T or I; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence the amino acid X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1is selected from A or T, wherein the amino acid residue X2is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4 is selected from T or I; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y;- CDR1 (AbM Numbering):a) having a length of 10 amino acids;b) having an aliphatic index of 20.00;c) having a grand average of hydropathicity (GRAVY) of 0.400, -0.010, preferably -0.010;d) comprising no or one positively-charged amino acid residues;e) comprising 40% hydrophobic, 0% or 10% basic and 50 or 60% neutral amino acids, suchas comprising 40% hydrophobic, and 60% neutral amino acids; or comprising 40% hydrophobic, 10% basic and 50% neutral amino acids; f) consisting of a polar neutral amino acid, a basic or polar neutral amino acid, twohydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; such as consisting of two polar neutral amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; or consisting of a polar neutral amino acid, a basic amino acid, two hydrophobic amino acid, four polar neutral amino acid, and two hydrophobic amino acid, preferably in that order; and / or g) comprising at least one, preferably all of the amino acids G, A, F, S, Y, A, M, and / orand / or optionally the amino acid R. Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 322 or 325;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 322 or 325 c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 322 or 325; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:d) the amino acid sequence of SEQ ID NOs: 323, 326, 327,e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 323, 326, 327; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 323, 326, 327. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: - CDR2 (AbM numbering) consists of an amino acid sequence selected from: a) the amino acid sequence of SEQ ID NO: 325; b) amino acid sequences that have at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 325; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 325; and - CDR3 (AbM numbering) consists of an amino acid sequence selected from: d) the amino acid sequence of SEQ ID NOs: 326; e) amino acid sequences that have at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 326; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 326. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: - CDR2 (AbM numbering) consists of an amino acid sequence selected from: a) the amino acid sequence of SEQ ID NO: 322; b) amino acid sequences that have at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 322; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 322; and - CDR3 (AbM numbering) consists of an amino acid sequence selected from: d) the amino acid sequence of SEQ ID NOs: 323; e) amino acid sequences that have at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 323; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 323. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: - CDR2 (AbM numbering) consists of an amino acid sequence selected from: a) the amino acid sequence of SEQ ID NO: 325; b) amino acid sequences that have at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 325; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 325; and - CDR3 (AbM numbering) consists of an amino acid sequence selected from: d) the amino acid sequence of SEQ ID NOs: 327; e) amino acid sequences that have at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 327; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 327. Preferably, the CDR2 and CDR3 sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR2 sequences of SEQ ID NOs: 322, or 325 and / or the CDR3 sequences of SEQ ID NOs: 323, 327, 326. In some embodiments, the ISVD comprises a CDR2 and CDR3 (AbM numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDR2 and CDR3 of the ISVD with the amino acid sequence selected from SEQ ID NOs: 115-117, 160-170. In one embodiment, the ISVD comprises a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 322 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 323. In another embodiment, the ISVD comprises a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 325 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 327. In another embodiment, the ISVD comprises a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 325 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 326. The SEQ ID NOs for the CDR sequences referred to above are based on the CDR definition according to the AbM definition (see Table A-8). It is noted that the SEQ ID NOs for the CDR sequences defined according to the Kabat definition can likewise be used (see Table A-9). Accordingly, the ISVDs provided by the present technology, specifically binding to CEACAM5 as described above using the AbM definition, can be also described using the Kabat definition. In some embodiments, the ISVDs specifically binding to this epitope on CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of X1X2SWRSX3X4TVYX5DSVKG (SEQ ID NO: 329); whereinthe amino acid residue X1 is selected from A or T, wherein the amino acid residue X2is selected from L or I, wherein the amino acid residue X3is selected from G or E, wherein the amino acid residue X4 is selected from T or I, and wherein the amino acid residue X5 is selected from G or A; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of X1X2SWRSX3X4TVYX5DSVKG (SEQ ID NO: 329); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3is selected from G or E, wherein the amino acid residue X4is selected from T or I, and wherein the amino acid residue X5is selected from G or A; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of X1X2SWRSX3X4TVYX5DSVKG (SEQ ID NO: 329); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3is selected from G or E, wherein the amino acid residue X4is selected from T or I, and wherein the amino acid residue X5is selected from G or A; and- CDR3 (Kabat numbering) consists of an amino acid sequence selected from:d) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4is selected from N or K, and wherein the amino acid residue X5is selected from F or Y; e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4is selected from N or K, and wherein the amino acid residue X5is selected from F or Y; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 330, 331, 332;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 330, 331, 332; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 330, 331, 332; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:d) the amino acid sequence of SEQ ID NOs: 323, 326, 327;e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 323, 326, 327; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 323, 326, 327. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 330;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 330; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 330; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:d) the amino acid sequence of SEQ ID NOs: 323;e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 323; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 323. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein:- CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 331;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 331; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 331; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:d) the amino acid sequence of SEQ ID NOs: 326;e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 326; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 326. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 331;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 331; c) amino acid sequences that have3, 2, or 1 amino acid difference with the amino acidsequence of SEQ ID NO: 331; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:d) the amino acid sequence of SEQ ID NOs: 327;e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 327; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 327. In some embodiments, the ISVD comprises 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 332;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 332; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 332; and -CDR3 (Kabat numbering) consists of an amino acid sequence selected from:d) the amino acid sequence of SEQ ID NOs: 327;e) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 327; f) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 327. Preferably, the CDR2 and CDR3 sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR2 sequences of SEQ ID NOs: 330, 331, 332; and / or the CDR3 sequences of SEQ ID NOs: 323, 327, 326. In one embodiment, the ISVD comprise a CDR2 and CDR3 (Kabat numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDR2 and CDR3 of the ISVD with the amino acid sequence selected from SEQ ID NOs: 115-117, 160-170. In one embodiment, the ISVD comprises a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 330 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 323. In another embodiment, the ISVD comprises a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 331 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 326. In another embodiment, the ISVD comprises a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 331 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 327. In another embodiment, the ISVD comprises a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 332 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 327. Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acidresidue X is selected from R or G; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acid residue X is selected from R or G; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GXAFSTYTMA (SEQ ID NO: 318), wherein the amino acid residue X is selected from R or G; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the aminoacid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4is selected from T or I; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3is selected from G or E and wherein the amino acid residue X4 is selected from T or I; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence the amino acid X1X2SWRSX3X4TV (SEQ ID NO: 319); wherein the amino acid residue X1is selected from A or T, wherein the amino acid residue X2is selected from L or I, wherein the amino acid residue X3 is selected from G or E and wherein the amino acid residue X4 is selected from T or I; and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3is selected from T or R and wherein the amino acid residue X4is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3is selected from T or R and wherein the amino acid residue X4is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4is selected from N or K, and wherein the amino acid residue X5is selected from F or Y. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 318, 319, and / or 320. In one embodiment, the ISVD comprise CDRs (AbM numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 115-117, 160-170. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 321, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 322 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 323. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 324, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 325 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 326. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 324, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 325 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 327. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315005F01 (SEQ ID NO: 115), A0315006F03 (SEQ ID NO: 116), A0315002G08 (SEQ ID NO: 117) and sequence optimized variants thereof in Table A-5 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A031500333 (SEQ ID NO: 160); A031500334 (SEQ ID NO: 161), A031500335 (SEQ ID NO: 162), A031500336 (SEQ ID NO: 163), A031500337 (SEQ ID NO: 164), A031500338 (SEQ ID NO: 165), A031500339 (SEQ ID NO: 166), A031500340 (SEQ ID NO: 167), A031500341 (SEQ ID NO: 168), A031500342 (SEQ ID NO: 169), or A031500343 (SEQ ID NO: 170) (see Table A-2, Table A-5). In another embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315005F01 (SEQ ID NO: 115), A0315006F03 (SEQ ID NO: 116), A0315002G08 (SEQ ID NO: 117) (see Table A-2). The SEQ ID NOs for the CDR sequences referred to above are based on the CDR definition according to the AbM definition (see Table A-8). It is noted that the SEQ ID NOs for the CDR sequences defined according to the Kabat definition can likewise be used (see Table A-9). Accordingly, the ISVDs provided by the present technology, specifically binding to CEACAM5 as described above using the AbM definition, can be also described using the Kabat definition. As such in one embodiment, the ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of TYTMA (SEQ ID NO: 328);b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of TYTMA (SEQ ID NO: 328); c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences of TYTMA (SEQ ID NO: 328); and- CDR2 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of X1X2SWRSX3X4TVYX5DSVKG (SEQ ID NO: 329); whereinthe amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E, wherein the amino acid residue X4 is selected from T or I, and wherein the amino acid residue X5is selected from G or A; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of X1X2SWRSX3X4TVYX5DSVKG (SEQ ID NO: 329); wherein the amino acid residue X1 is selected from A or T, wherein the amino acid residue X2 is selected from L or I, wherein the amino acid residue X3 is selected from G or E, wherein the amino acid residue X4 is selected from T or I, and wherein the amino acid residue X5 is selected from G or A; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of X1X2SWRSX3X4TVYX5DSVKG (SEQ ID NO: 329); wherein the amino acid residue X1is selected from A or T, wherein the amino acid residue X2is selected from L or I, wherein the amino acid residue X3is selected from G or E, wherein the amino acid residue X4 is selected from T or I, and wherein the amino acid residue X5 is selected from G or A; and- CDR3 (Kabat numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein theamino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1is selected from Q or E, wherein the amino acid residue X2is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QX1X2GAISYNX3X4GX5FY (SEQ ID NO: 320); wherein the amino acid residue X1 is selected from Q or E, wherein the amino acid residue X2 is selected from Y or F, wherein the amino acid residue X3 is selected from T or R and wherein the amino acid residue X4 is selected from N or K, and wherein the amino acid residue X5 is selected from F or Y. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 328, 329, and / or 320, as defined above. In one embodiment, the ISVD comprise CDRs (Kabat numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 115-117, 160-170. In one embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 328, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 330 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 323. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 328, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 331 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 326. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 328, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 331 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 327. In another embodiment, the ISVD comprises a CDR1 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 328, a CDR2 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 332 and a CDR3 (Kabat numbering) that is the amino acid sequence of SEQ ID NO: 327. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315005F01 (SEQ ID NO: 115), A0315006F03 (SEQ ID NO: 116), A0315002G08 (SEQ ID NO: 117) and sequence optimized variants thereof in Table A-5 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A031500333 (SEQ ID NO: 160); A031500334 (SEQ ID NO: 161), A031500335 (SEQ ID NO: 162), A031500336 (SEQ ID NO: 163), A031500337 (SEQ ID NO: 164), A031500338 (SEQ ID NO: 165), A031500339 (SEQ ID NO: 166), A031500340 (SEQ ID NO: 167), A031500341 (SEQ ID NO: 168), A031500342 (SEQ ID NO: 169), or A031500343 (SEQ ID NO: 170) (see Table A-2, Table A-5). In another embodiment, the ISVD comprises or consists of the full amino acid sequence of A0315005F01 (SEQ ID NO: 115), A0315006F03 (SEQ ID NO: 116) and A0315002G08 (SEQ ID NO: 117) (see Table A-2). In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 115, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 115. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequenceidentity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 116,wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding toCEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 116.In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequenceidentity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 117,wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding toCEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 117.In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 160, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 160. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 161, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 161. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 162, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 162. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 163, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 163. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 164, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 164. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 165, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 165. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 166, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 166. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 167, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 167. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 168, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 168. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 169, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 169. In another embodiment, the ISVD specifically binding to human CEACAM5 may have a sequence identity of more than 90%, such as more than 95% or even more than 99%, with SEQ ID NO: 170, wherein the CDRs are as defined above. In one embodiment, the ISVD specifically binding to CEACAM5 comprises or consists of the amino acid sequence of SEQ ID NO: 170. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 115-117, 160-170, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 115-117, 160-170, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 10-fold lower affinity (KD). Preferably, the ISVD specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when such an ISVD specifically binding to CEACAM5 has 3, 2 or 1 amino acid difference in at least one CDR relative to a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, or CEACAM7. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 115-117, 160-170, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 115-117, 160-170,, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have at least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 10-fold lower affinity (KD). Preferably, the ISVD specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the CDRs of such an ISVD specifically binding to CEACAM5 have least 90% amino acid sequence identity, at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, with a corresponding reference CDR sequence (above), the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, or CEACAM7. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 115-117, 160-170, the ISVD has at least (essentially) the same binding affinity to human CEACAM5 compared to one of the VHHs with SEQ ID NOs: 115-117, 160-170, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 115-117, 160-170, the ISVD has at least (essentially) the same binding affinity to cyno CEACAM5 compared to one of the VHHs with SEQ ID NOs: 115-117, 160-170, wherein the binding affinity is measured using the same method, such as, e.g., SPR. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 115-117, 160-170, the ISVD still specifically binds to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 115-117, 160-170, the ISVD still specifically binds to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 10-fold lower affinity (KD). Preferably, the ISVD specifically binds to human and cyno CEACAM5 and does not bind to other members of the CEACAMs family. In another embodiment, when the ISVD specifically binding to human CEACAM5 has a sequence identity of more than 90%, such as more than 95% or more than 99%, with one of the VHHs with SEQ ID NOs: 115-117, 160-170, the ISVD still specifically binds to human and cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, or CEACAM7. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a dissociation constant (KD) of 10-7to 10-11moles / litre or less, and preferably 10-8to 10-10moles / litre or less and more preferably 5x10-8to 6x10-10moles / litre, even more preferably wherein the ISVD specifically binds to human CEACAM5 with a KD of about 1.66x10-9moles / litre, 5.08x10-10moles / litre or 3.37x10-9moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 1x105M-1s-1and 5x106M-1s-1, such as between 5x105M-1s-1and 5x106M-1s-1, even more preferably of about 1.93x106M-1s-1, 1.42x106M-1s-1, or 1.94x106M-1s-1as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 with a koff rate between 10-2s-1(t1 / 2=0.69 s) and 10-6s-1(providing a near irreversible complex with a t1 / 2 of multiple days), preferably between 10-2s-1and 1x10-5s-1, more preferably between 1x10-2s-1and 1x10-4s-1, such as between 7x10-3s-1and 5x10-4s-1even more preferably of about 3.21x10-3s-1, 7.23x10-4s-1, or 6.55 x10-3s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a dissociation constant (KD) of 10-7to 10-10moles / litre or less, and preferably 10-8to 10-9moles / litre or lessand more preferably 5x10-8to 10-9moles / litre or less, more preferably wherein the ISVD specifically binds to human CEACAM5 with a KDof about 1.8x10-9moles / litre, 4.48x10-9moles / litre or 1.2x10-8moles / litre, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a kon-rate of between 104M-1s-1to about 107M-1s-1, preferably between 105M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 5x106M-1s-1, such as between 1x105M-1s-1and 2x106M-1s-1, even more preferably of about 1.32x106M-1s-1, 1.08x106M-1s-1, or 1.97x105M-1s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to cyno CEACAM5 with a koffrate between 10-2s-1(t1 / 2=0.69 s) and 10-5s-1(providing a near irreversible complex with a t1 / 2 of multiple days), 10-2s-1and 10-4s-1, more preferably between 5x10-3s-1and 1x10-4s-1, such as between 5x10-3s-1and 5x10-3s-1, even more preferably of about 2.36x10-3s-1, 4.86x10-3s-1, or 2.37x10-3s-1, as determined by SPR. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5 and cyno CEACAM5 with less than 10-fold difference in affinity (KD). In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and binds to other members of the CEACAMs family with a at least 10-fold lower affinity (KD). In preferred embodiments, the immunoglobulin single variable domains specifically bind to human and cyno CEACAM5 and do not bind to other members of the CEACAMs family. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human and cyno CEACAM5 and do not bind to human and cyno CEACAM1, CEACAM6, or CEACAM7. A preferred assay for measuring binding and internalization of the ISVD (or polypeptide comprising the ISVD) to CEACAM5 exposed on a cell surface is a FACS assay. For instance, the ISVDs or polypeptides of the present invention can be applied to cancer cell lines overexpressing CEACAM5, such as a BxPC-3 cell line, which is a human pancreatic adenocarcinoma cell line. VHH bound to human CEACAM5 can be detected with a fluorophore- labelled anti-VHH antibody and the cells can be analyzed with a flow cytometer to evaluate the binding properties of ISVDs or polypeptides of the present invention. In some embodiments, the immunoglobulin single variable domains of the present technology specifically bind to human CEACAM5. For example, in a FACS binding assay with a BxPC-3 cell line expressing human CEACAM5., the immunoglobulin single variable domains of the present technology may have EC50 values of 10-7M or lower, more preferably of 10-8M or lower, or even of 10-9M or lower. For example, in such FACS assay, the immunoglobulin single variable domains of the present technology may have EC50 values between 10-11M and 10-7M, such as between 10-10M and 10-8M, between 10-9M and 10-8M or between 10-9M and 5x10-8M. In some embodiments, the immunoglobulin single variable domains of the present technology has an CEACAM5-mediated internalization potency (EC50 value) of 10-7M or lower, more preferably of 5x10-8M or lower, or even of 10-8M or lower, such as between 10-7M and 10-10M, between 10-7M and 10-9M, between 5x10-8M and 10-9M, for example, as measured in a FACS internalization assay on BxPC-3 cells expressing human CEACAM5.5.2.5 Embodiment 5 -Family 3Specific examples of ISVDs specifically binding to CEACAM5 are ISVDs that comprise 4 framework regions (FR1 to FR4, respectively) and three complementarity determining regions (CDR1 to CDR3, respectively), wherein: -CDR1 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of GLTFSTYTXG (SEQ ID NO: 333), wherein the amino acidresidue X is selected from V or M;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of GLTFSTYTXG (SEQ ID NO: 333), wherein the amino acid residue Xis selected from V or M; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence GLTFSTYTXG (SEQ ID NO: 333), wherein the amino acid residue X isselected from V or M; and -CDR2 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence of SX1IX2SGSNTX3 (SEQ ID NO: 335); wherein the aminoacid residue X1 is selected from I or M, wherein the amino acid residue X2 isselected from W or Y, and wherein the amino acid residue X3 is selected from Vor L; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence SX1IX2SGSNTX3 (SEQ ID NO: 335); wherein the amino acid residue X1is selected from I or M, wherein the amino acid residue X2 is selected from W or Y,and wherein the amino acid residue X3 is selected from V or L;c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence SX1IX2SGSNTX3 (SEQ ID NO: 335); wherein the amino acid residue X1is selected from I or M, wherein the amino acid residue X2 is selected from W or Y,and wherein the amino acid residue X3 is selected from V or L;and -CDR3 (AbM numbering) consists of an amino acid sequence selected from:a) the amino acid sequence QHFGPX1SLTTRGYX2Y (SEQ ID NO: 338); wherein theamino acid residue X1 is selected from V or I, and wherein the amino acid residueX2 is selected from Y or F; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence QHFGPX1SLTTRGYX2Y (SEQ ID NO: 338); wherein the amino acidresidue X1 is selected from V or I, and wherein the amino acid residue X2 is selectedfrom Y or F; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence QHFGPX1SLTTRGYX2Y (SEQ ID NO: 338); wherein the amino acidresidue X1 is selected from V or I, and wherein the amino acid residue X2 is selectedfrom Y or F. Preferably, the CDR sequences have at least 90% amino acid sequence identity, more preferably at least 95% amino acid sequence identity, such as 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the CDR sequences of SEQ ID NOs: 333, 335, and / or 338. In one embodiment, the ISVD comprise CDRs (AbM numbering) with an amino acid sequence that has at least 70% amino acid sequence identity, preferably at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with the amino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 118-119, 171-174. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 1, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 336 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 339. In one embodiment, the ISVD comprises a CDR1 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 334, a CDR2 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 337 and a CDR3 (AbM numbering) that is the amino acid sequence of SEQ ID NO: 340. Specific examples of such ISVDs that specifically bind to CEACAM5 have one or more, or all, framework regions as indicated for A0315002G06 (SEQ ID NO: 118), A0315002C10 (SEQ ID NO: 119), and sequence optimized variants thereof in Table A-6 (in addition to the CDRs as defined above). In one embodiment, the ISVD comprises or consists of the full amino acid sequence of A031500010 (SEQ ID NO: 171), A031500011 (SEQ ID NO: 172), A0...

Claims

CLAIMS1. An immunoglobulin single variable domain (ISVD) specifically binding human CEACAM5, thatessentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which: -CDR1 (AbM numbering) has an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 1;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 1; and c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequences of SEQ ID NO: 1; and -CDR2 (AbM numbering) has an amino acid sequence selected from:a) the amino acid sequence of SEQ ID NO: 2;b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of SEQ ID NO: 2; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of SEQ ID NO: 2; and -CDR3 (AbM numbering) has an amino acid sequence selected from:a) the amino acid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein theamino acid residue X is selected from N, A, F, G, I, L, Y or H; b) amino acid sequences that have at least 80% amino acid identity with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H; c) amino acid sequences that have 3, 2, or 1 amino acid difference with the aminoacid sequence of QHFGPIGLTTRGYXY (SEQ ID NO: 230), wherein the amino acidresidue X is selected from N, A, F, G, I, L, Y or H.

2. The ISVD according to claim 1, in which the amino acid sequences of the CDRs (AbMnumbering) have at least 80% amino acid sequence identity, more preferably at least 90% amino acid sequence identity, such as 95% amino acid sequence identity or 99% amino acid sequence identity or more, or even essentially 100% amino acid sequence identity with theamino acid sequences of the CDRs of the ISVD with the amino acid sequence selected from SEQ ID NOs: 8, 31, 32, 150-159.

3. The ISVD according to any one of claims 1 or 2, in which^ CDR1 consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 consists of one of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 consists of the amino acid sequence of SEQ ID NO: 3,or in which ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of one of the amino acid sequences of SEQ ID NO:2; and ^CDR3 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 33,or in which ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYAY(SEQ ID NO: 249); or in which ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYFY(SEQ ID NO: 250); or in which ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYGY(SEQ ID NO: 251), or in which ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYIY(SEQ ID NO: 254); or in which^ CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO: 1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYLY(SEQ ID NO: 252); or in which ^CDR1 (AbM numbering) consists of the amino acid sequence of SEQ ID NO:1;^ CDR2 (AbM numbering) consists of the amino acid sequences of SEQ ID NO: 2; and^ CDR3 (AbM numbering) consists of the amino acid sequence of QHFGPIGLTTRGYYY(SEQ ID NO: 253).

4. The ISVD according to any one of claims 1 to 3, that essentially consists of a VHH, a humanizedVHH, a camelized VH, a domain antibody, a single domain antibody, or a dAb.

5. The ISVD according to any one of claims 1 to 4, wherein the ISVD specifically binds to humanCEACAM5: a. with a dissociation constant (KD) of 10-7 to 10-11 moles / litre or less, and preferably 10-8 to10-10moles / litre or less and more preferably 1x10-8to 1x10-9moles / litre or less, even more preferably wherein the ISVD specifically binds to human CEACAM5 with a KDof about 1.34x10-9moles / litre or 1.24x10-9moles / litre, and / or b. with a kon rate of between 104 M-1s-1 to about 107 M-1s-1, preferably between 105 M-1s-1and 107M-1s-1, more preferably between 105M-1s-1and 106M-1s-1, such as between 1x105M-1s-1and 8x105M-1s-1, even more preferably of about 3.17x105M-1s-1or about7.16x105M-1s, and / or c. with a koff rate between 10-3 s-1 and 10-6 s-1, preferably between 10-2 s-1 and 1x10-5 s-1, morepreferably between 5x10-3s-1and 1x10-4s-1, such as between 5x10-3s-1and 5x10-4s-1, even more preferably of about 4.24x10-3s-1or 8.85x10-4s-1, as determined by Surface Plasmon Resonance.

6. The ISVD according to any one of claims 1 to 5, wherein the ISVD specifically binds to humanand cyno CEACAM5 and does not bind to CEACAM1, CEACAM6, CEACAM7 and CEACAM8 or other members of the CEACAMs family.

7. The ISVD according to any one of claims 1 to 6, wherein the ISVD internalizes upon binding toCEACAM5.

8. The ISVD according to any one of claims 1 to 7, which is a humanized ISVD that is chosen fromthe group consisting of SEQ ID NOs: 31, 32, 150-159 or from the group consisting of amino acid sequences that have more than 80%, preferably more than 90%, more preferably more than 95%, such as 99% or more amino acid sequence identity with at least one of the amino acid sequences of SEQ ID NOs: 8, 31, 32, 150-159.

9. A polypeptide or construct that comprises or essentially consists of one or more ISVDsaccording to any one of claims 1 to 8, and optionally further comprises one or more other groups, residues, moieties or binding units, optionally linked via one or more linkers, in which said one or more other groups, residues, moieties or binding units are ISVDs.

10. The polypeptide or construct according to claim 9, in which said one or more other groups,residues, moieties or binding units provide the polypeptide or construct with increased half- life, compared to the ISVD without the one or more other groups, residues, moieties or binding units.

11. The polypeptide or construct according to claim 10, in which said one or more other groups,residues, moieties or binding units that provides the polypeptide or construct with increased half-life is an ISVD that specifically binds human serum albumin, optionally wherein said ISVD that specifically binds human serum albumin is selected from the group consisting of ALB8 (SEQ ID NO: 47), ALB23 (SEQ ID NO: 48), ALBX00001 (SEQ ID NO: 61) and ALB23002 (SEQ ID NO: 62).

12. A nucleic acid that encodes an ISVD according to any one of claims 1 to 8, or a polypeptideaccording to any one of claims 9 to 11.

13. A non-human host or host cell that expresses, or that under suitable circumstances is capableof expressing, an ISVD according to any one of claims 1 to 8, or a polypeptide according to any one of claims 9 to 10; and / or that comprises the nucleic acid according to claim 12.

14. A method for producing an ISVD according to any one of claims 1 to 8, or a polypeptideaccording to any one of claims 9 to 11, at least comprising the steps of: a) expressing, in a suitable non-human host cell or host organism or in another suitableexpression system, a nucleic acid according to claim 11; optionally followed by: b) isolating and / or purifying the ISVD according to any one of claims 1 to 8, or thepolypeptide according to any one of claims 9 to 11.

15. A composition comprising at least one ISVD according to any one of claims 1 to 8, at least onepolypeptide or construct according to any one of claims 9 to 11, or at least one nucleic acid according to claim 12; which optionally is a pharmaceutical composition, that further comprises at least one pharmaceutically acceptable carrier, diluent or excipient and / or adjuvant, and that optionally comprises one or more further pharmaceutically active polypeptides and / or compounds.

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