Triple-payload antibody-drug conjugates (ADCS)

Abstract

Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e..g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin such asMMAE (Monomethyl auristatin E). Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease.

Description

[0001] New PCT-Patent Application Araris Biotech AG Vossius Ref.: AG3709 PCT / A BS TRIPLE-PAYLOAD ANTIBODY-DRUG CONJUGATES (ADCS) Related Applications The present invention claims the benefit of EP 24187879.2, filed July 10, 2024, EP 24 189861.8, filed July 19, 2024, PCT / EP2024 / 079076 filed October 15, 2024, and EP 25170920.0, filed April 16, 2025, the contents of which are incorporated herein by reference in their entireties for all purposes. Background of Invention DNA topoisomerases are essential enzymes that stabilize DNA supercoiling and resolve entanglements. Topoisomerase inhibitors have been widely used as anti- cancer drugs for the past 20 years. Due to their selectivity as topoisomerase I (TOP1) inhibitors that trap TOP1 cleavage complexes, camptothecin and its derivatives are promising anti-cancer drugs. To increase accumulation of TOP1 inhibitors in cancer cells through the targeting of tumors, TOP1 inhibitor antibody–drug conjugates (TOP1- ADCs) have been developed and marketed. Some TOP1-ADCs have shown enhanced therapeutic efficacy compared to prototypical anti-cancer ADCs (Han S. et al, 2022, Pharmaceutics, 14, 1707). One of the most prominent examples of TOP1-ADCs is DS-8201a (ENHERTU®), a HER2 targeting ADC with a novel DNA topoisomerase I inhibitor that demonstrated impressive antitumoral activity in a broad selection of HER2 positive models and favorable safety profiles (Ogitani et al.2016, Clin Cancer Res; 22(20)), leading to its approval for several types of HER2 positive breast cancer types, non-small cell lung cancers and gastric / gastroesophageal junction adenocarcinomas. Notwithstanding these clinical advances, many patients remain resistant or non- responsive to available ADC therapies, and there remains an urgent need to provide additional options for the effective treatment of cancer including anti-cancer drugs with improved anti-tumor effects. Detailed Description of the Invention The present invention relates, at least in part, to an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable (e.g., a camptothecin cytotoxic molecule which is cell-permeable); as a second payload a topoisomerase I inhibitor which is not cell-permeable (e.g., a camptothecin cytotoxic molecule which is not cell-permeable); and as a as a third payload a toxin or a cytotoxin (e.g., an auristatin such as MMAE (Monomethyl auristatin E)). In one aspect, the present invention relates to a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. In another aspect, the present invention relates to said ADC for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease. The present invention is based, at least in part, on the surprising finding that an ADC comprising an anti-tumor targeting antibody and a combination of at least two different topoisomerase I inhibitors, e.g., a topoisomerase I inhibitor that is cell-permeable and a topoisomerase I inhibitor that is not cell-permeable, exhibits a significantly improved anti-tumor effect compared to an ADC comprising the same targeting antibody but with a single type of topoisomerase I inhibitor. For example, and as demonstrated in more detail in the Examples section below, an ADC having the same HER-2 targeting antibody as used in DS-8201a, but having 2 exatecans (an exemplary payload that shows cell permeation) and 2 Gly-exatecans (an exemplary payload that shows no cell permeation due to a glycine residue linked to exatecan) per antibody (i.e., a DAR of 4), has a synergistic effect over DS-8201a. Without being bound to any particular theory, it is thought that the cell impermeableGly-exatecan payload is able to kill target- positive cells very efficiently by accumulating within cell, whereas the cell permeable exatecan cytotoxic payload has a bystander activity that can kill not only the targeted cancer cells but also neighboring cells that might not express the target, thereby addressing tumor heterogeneity and reducing the risk of tumor relapse. Furthermore, by combining these two different topoisomerase I inhibitors with another cytotoxic payload the disclosure demonstrates, quite unexpectedly, that one can further increase the anti-tumor activity of the resulting ADCs. Accordingly, in one aspect, the present invention thus relates to: an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e.g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin such as MMAE (Monomethyl auristatin E). In certain aspects, the present invention relates to an antibody drug conjugate (ADC) which comprises the following components, e.g., an antibody, and a linker, wherein the linker comprises a topoisomerase I inhibitor as a first and second payload, wherein the topoisomerase I inhibitor of the first payload is cell-permeable and wherein the topoisomerase I inhibitor of the second payload is not cell-permeable, and a toxin (e.g., cytotoxin) as a third payload. In certain embodiments, the present invention relates to an antibody drug conjugate (ADC) which comprises the following components, i.e., an antibody, and a linker, where the linker comprises, a camptothecin cytotoxic molecule as a first and second payload, respectively, wherein the camptothecin cytotoxic molecule of the first payload is cell-permeable and wherein the camptothecin cytotoxic molecule of the second payload is not cell-permeable, and an auristatin as a third payload, e.g., MMAE (Monomethyl auristatin E). So that the disclosure may be more readily understood, select terms are defined below. As used herein, the term "antibody-drug conjugate" (ADC) refers to a targeted therapy that combines an antibody specific to a particular antigen with a linker comprising a drug or payload (e.g., a cytotoxin). The antibody directs the drug or payload to cells expressing the target antigen, such as cancer cells, allowing for precise delivery of the drug or payload to the desired cells, thereby minimizing damage to healthy tissues. In the present application, an antibody-drug conjugate is also referred to as an "antibody- payload conjugate." The term “antibody” herein is used in the broadest sense and specifically covers monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) formed from at least two intact antibodies, and antibody fragments so long as they exhibit the desired biological activity. The terms “antibody” and “antibodies” broadly encompass naturally occurring forms of antibodies (e.g., IgG, IgA, IgM, IgE). In certain embodiments, the antibody is a monoclonal antibody. The antibody can be of human origin, but likewise from mouse, rat, goat, donkey, hamster, or rabbit. In case the conjugate is for therapy, a murine or rabbit antibody may optionally be chimeric or humanized. In certain embodiments, the antibody is a bispecific antibody (e.g., DVD-IgG, crossMab, appended IgG – HC fusion) or biparatopic. See Brinkmann and Kontermann; Bispecific antibodies; Drug Discov Today; 2015; 20(7); p.838-47, for an overview. The term “antibody” further encompasses antigen-binding fragments of antibodies. The term "antibody fragment", as used herein, refers to a portion of an antibody molecule that retains the ability to specifically bind to an antigen. These fragments are derived from full-length antibodies and include, but are not limited to, Fab (Fragment antigen- binding), F(ab')2, scFv (single-chain variable fragment), dsFv (disulfide-stabilized Fv), Fab', diabody, nanobody (VHH or single-domain antibody), and domain antibodies (dAbs). Antibody fragments are engineered to maintain the antigen-binding function while being smaller and more versatile than full-length antibodies, making them particularly useful for therapeutic, diagnostic, and research applications due to their enhanced tissue penetration, reduced immunogenicity, and ease of production and manipulation. In certain embodiments, an ADC of the invention comprises a linker (e.g., a peptide linker) that is conjugated to glutamine residue 295 (Q295) in the CH2 domain of an IgG antibody. Accordingly, in certain embodiments, the antibody or antibody fragment of the ADC comprises a CH2 domain. Fragments or recombinant variants of antibodies comprising the CH2 domain may be, for example, antibody formats comprising mere heavy chain domains (shark antibodies / IgNAR (VH-CH1-CH2-CH3-CH4-CH5)2 or camelid antibodies / hcIgG (VH-CH2-CH3)2) scFv-Fc (VH-VL-CH2-CH3)2 Fc fusion peptides, comprising an Fc domain and one or more receptor domains. In a particular embodiment, the antibody is an IgG antibody. By "IgG" as used herein is meant a polypeptide belonging to the class of antibodies that are substantially encoded by a recognized immunoglobulin gamma gene. In humans, IgG comprises the subclasses or isotypes IgG1, IgG2, IgG3, and IgG4. In mice, IgG comprises IgG1, IgG2a, IgG2b, IgG3. Full-length IgGs consist of two identical pairs of two immunoglobulin chains, each pair having one light and one heavy chain, each light chain comprising immunoglobulin domains VL and CL, and eachheavy chain comprising immunoglobulin domains VH, C 1 (also called CH1), C 2 (alsocalled CH2), and O 3 (also called CH3). In the context of human IgG1, "CH1" refers topositions 118-215, CH2 domain refers to positions 231-340 and CH3 domain refers to positions 341-447 according to the EU index as in Kabat. IgG1 also comprises a hinge domain which refers to positions 216-230 in the case of IgG1. In certain embodiments, the antibody is an IgG1 or IgG4 antibody. In one embodiment, the antibody is a human IgG1 antibody. In a particular embodiment, the antibody is an antibody that comprises a mutation thatreduces, ablates or eliminates Fc R binding.Mutations in an antibody (e.g., in the constant region (e.g., Fc region) of the heavychain of an antibody (e.g., Fc mutations) that reduce, ablate or eliminate Fc R bindingare known in the art and are contemplated in the context of the present invention. Without being bound to theory, a combination of the mutations Leu234Ala and Leu235Ala (according to Kabat positions numbering) are known to reduce or eliminatebinding to Fc RI, IIa, and IIIa for both IgG1 and IgG4. This combination of mutationsare commonly referred to as “LALA mutations". This type of mutation is commonlyknown in the art to reduce the antibody’s effector function. The article of Liu et al.,Antibodies 9(4):64 (2020)) reviews these and other Fc-engineering for modulated effector functions of antibodies, in particular, for improving the performance of antibodies in cancer treatment. Accordingly, in an exemplary embodiment, the antibody is an antibody, e.g., an IgG antibody, comprising at Kabat position 234 an A and / or at Kabat position 235 an A. In other embodiments, the antibody is an IgG1 or an IgG4 antibody comprising at Kabat position 234 an A and / or at Kabat position 235 an A. In certain embodiments, the linker comprises a cytotoxic molecule or toxin as a payload. The terms "toxin" and “cytotoxic molecule” are known in the art and generally relate to any compound that is poisonous to a cell or organism. The terms “poison” or “poisonous” are commonly known in the art and refer in general terms to a substance that is harmful or lethal to a living organism in terms that it causes death, injury or harm to an organism or cell and / or triggers apoptosis of the cells. In certain embodiments, the toxin / cytotoxic molecule may be produced by a cell or an organism. However, a toxin / cytotoxic molecule may also be a chemical derivative or analog of a toxin that is produced by a cell or an organism. In general, toxins / cytotoxic molecules are understood to be, without limitation, small molecules, peptides, or proteins. Specific examples are neurotoxins, necrotoxins, hemotoxins and cytotoxins. In certain embodiments, the toxin / cytotoxic molecule is a toxin / cytotoxic molecule that is used in the treatment of neoplastic diseases. That is, the toxin / cytotoxic molecule is conjugated to an antibody delivered to or into a malignant cell due to the target specificity of the antibody. In certain embodiments, the toxin / cytotoxic molecule is a topoisomerase I inhibitor, e.g., a camptothecin. A “topoisomerase I inhibitor” as used herein is a molecule that functions as an inhibitor of a type I topoisomerase or topoisomerase I (TOP1) enzyme, e.g., a human TOP1 enzyme. TOP1 enzymes play an important role in DNA replication and transcription by relieving torsional stress in DNA, e.g., by cutting one of the two strands of the DNA, relaxing the strand, and reannealing the strand. In certain embodiments, a TOP1 inhibitor prevents the proper religation of DNA strands after they have been temporarily cleaved by TOP1, leading to DNA damage, cell cycle arrest, and / or programmed cell death (apoptosis) of a tumor cell (see, e.g., Pommier, DNA Topoisomerase I Inhibitors: Chemistry, Biology and Interfacial Inhibition, Chem Rev. 2009 Jul;109(7):2894–2902). Topoisomerase inhibitors may include camptothecins or non-camptothecins. Non-limiting examples of non-camptothecin topoisomerase I inhibitors are indolocarbazoles, dibenzonaphthyridines and indenoisoquinolones. The term "camptothecin" as used herein is intended to mean a camptothecin or camptothecin derivative or camptothecin analogs that functions as a topoisomerase I inhibitor. Exemplary camptothecins have a planar pentacyclic ringstructure, that includes a pyrrolo[3,4- ]-quinoline moiety (rings A, B and C), conjugatedpyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring). Art-recognized camptothecins include, for example, topotecan, exatecan, DXd, irinotecan, belotecan, rubitecan, gimatecan, silatecan, cositecan, DX-8951f, SN38, BN 80915, lurtotecan, AZ0132, CPT1, CPT2, Dxd(1), Dxd(2), 9-nitrocamptothecin and aminocamptothecin. A variety of camptothecins have been described, including camptothecins used to treat human cancer patients. Several camptothecins are described, for example, in Kehrer et al.,Anticancer Drugs, 12 (2) : 89-105, (2001) or Li et al., ACS Med. Chem. Lett. 2019, 10,10, 1386–1392), which is incorporated by reference herein. In certain embodimentsthe camptothecin is the exatecan derivative shown as compound 10 in Li et al., ACSMed. Chem. Lett.2019, 10, 10, 1386–1392). In certain embodiments, the camptothecin derivative is exatecan. In certain embodiments, the camptothecin derivative is a glycinated exatecan (G-Exa; see e.g., FIG.4). In certain embodiments, a camptothecin cytotoxic molecule is used as a first and second payload, respectively, wherein the camptothecin cytotoxic molecule of the first payload is cell-permeable and wherein the camptothecin cytotoxic molecule of the second payload is not cell-permeable. Methods are known in the art to render a molecule (e.g., a camptothecin cytotoxic molecule) cell-permeable or not cell-permeable. In certain embodiments, and without being bound by theory, the camptothecin cytotoxic molecule of the second payload is rendered to be not cell-permeable by adding covalently a glycine residue to the primary amine on an F ring of a camptothecin cytotoxic molecule. In an exemplary embodiment, the glycinated camptothecin is a glycinated exatecan having the following structure: The skilled person is aware of additional, common strategies to reduce the cell- permeability of a drug. For example, as small uncharged lipophilic molecules are more likely to permeate across cell barriers than those which are charged and hydrophilic, modifications of topoisomerase 1 inhibitors which will increase the overall polarity and hydrophilicity (by adding charge through highly ionizable groups such as primary, secondary or tertiary amine, carboxylate, phosphonate, sulfonate, nitro, and others) will reduce the cell-permeability. Accordingly, in a particular embodiment, the invention relates to the antibody-payload conjugate or linker, wherein the second payload has been modified to reduce its cell permeability. In certain embodiments, Topoisomerase 1 inhibitors are modified to reduce their cell permeability by covalently linking the topoisomerase 1 inhibitor to molecules that will increase the overall polarity and / or hydrophilicity. In one embodiment, the polarity and / or hydrophilicity of the topoisomerase 1 inhibitors may be increased by covalently linking the topoisomerase 1 inhibitors to an amino acid residue, e.g., a glycine residue. Moreover, the capability of a molecule (e.g., the payload of an ADC) to be cell- permeable or not cell-permeable can be measured / determined by methods known in the art and as described herein. For example, this capability can be measured / determined as follows: The ADC of interest can be incubated under coculture conditions essentially as described by Ogitani et al. (Ogitani et al., 2016, Cancer Sci, 107,7, pp.1039-1046): Antigen-positive cells and antigen negative cells are cocultured in vitro, and upon incubation with the ADC cell viability is measured. If the ADC is able to kill preferentially the target positive cells, then the payload does not permeate to the adjacent antigen negative cells (“no bystander activity”), whereas if the ADC of interest kills both cells then the payload is cell permeable (“bystander activity”). A payload of an ADC or linker is considered “cell-permeable”, within the meaning of the present invention, if ADC incubation results in efficient killing of target positive cells and at least 70%, preferably 80%, more preferably 90% and most preferably more than 95% of the target negative cells under said coculture conditions. A payload of an ADC or linker is considered “not cell-permeable” or “cell impermeable”, within the meaning of the present invention, if ADC incubation results in efficient killing of target positive cells and less than 30%, preferably less than 20%, preferably less than 10% and most preferably less than 5% of the target negative cells under said coculture conditions. In a particular embodiment, the first payload, i.e., the cell-permeable topoisomerase 1 inhibitor, is exatecan: In some embodiments, the exatecan is attached via the primary amine on the F ring to a self-immolative moiety comprised in the linker to allow for the release of the fully active, chemically unmodified payload. In certain embodiments, the first payload is DXd: In certain embodiments, the DXd is attached to a peptide of the linker via a hydroxyl group. In certain embodiments, the DXd is linked to the C-terminal end of a peptide via an aminomethyl (AM) moiety, as described elsewhere herein. In certain embodiments, the first payload is belotecan: In certain embodiments, the belotecan is attached via an amine to a self-immolative moiety comprised in the linker to allow for the release of the fully active, chemically unmodified payload. In certain embodiments, the second payload is a modified exatecan, wherein the exatecan is linked via the primary amine on the F ring to a molecule that will increase the overall polarity and / or hydrophilicity, e.g., an amino acid residue, e.g., a glycine residue. The ADC or linker of the invention further comprises a third payload. In certain embodiments, the third payload is different in structure compared to the first and / or second payload. In certain embodiments, this third payload is not a topoisomerase I inhibitor which is cell-permeable and is not a topoisomerase inhibitor I which is not cell permeable as defined herein above. In certain embodiments, the third payload is not a camptothecin cytotoxic molecule which is cell-permeable; and is not a camptothecin cytotoxic molecule which is not cell- permeable. In certain embodiments, the third payload is a toxin, cytotoxin or a cytotoxic molecule. In a particular embodiment, the third payload is selected from the group consisting of: •a pyrrolobenzodiazepine (e.g., PBD);• an auristatin (e.g., MMAE, MMAF);• a maytansinoid (e.g., maytansine, DM1, DM4, DM21);• a duocarmycin;• a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor;• a tubulysin;• an enediyne (e.g., calicheamicin);• an anthracycline derivative (PNU) (e.g., doxorubicin);• a pyrrole-based kinesin spindle protein (KSP) inhibitor;• a cryptophycin;• a drug efflux pump inhibitor;• a sandramycin;• an antimetabolite or metabolite inhibitor, preferably a thymidylate synthaseinhibitor; •an amanitin (e.g., -amanitin);• a DNA damage repair inhibitor; and• a topoisomerase II inhibitor.In certain embodiments, the ADC or linker of the invention comprises a toxin as a third payload. In certain embodiments, the toxin is a tubulin polymerization-blocking agent or anti- mitotic drug. In certain embodiments, anti-mitotic agent or tubulin polymerization- blocking agent is an auristatin or auristatin derivative. Examples of auristatin or auristatin derivative include, but are not limited to, synthetic analogues of auristatin E (AE), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF) and dolastatin. In a particular embodiment, the third payload is an MMAE (Monomethyl auristatin E). In certain embodiments, the third payload may be a maytansinoid. As used herein, the term “maytansinoid” refers to a class of highly cytotoxic drugs originally isolated fromthe African shrub Maytenus ovatus and further maytansinol (Maytansinol) and C-3ester of natural maytansinol (US Pat. No. 4,151,042); C-3 ester analog of synthetic maytansinol (Kupchan et al., J. Med. Chem.21: 31-37, 1978; Higashide et al., Nature 270: 721-722, 1977; Kawai et al., Chem. Farm. Bull.32: 3441-3451; and US Pat. No. 5,416,064); C-3 esters of simple carboxylic acids (US Pat. 4,248,870; 4,265,814; 4,308,268; 4,308,269; 4,309,428; 4,317,821; 4,322,348; and 4,331,598); and C-3 esters with derivatives of N-methyl-L-alanine (U.S. Pat. Nos. 4,137,230; 4,260,608; and Kawai et al., Chem. Pharm Bull. 12: 3441, 1984). Exemplary maytansinoids include maytansine, DM1, DM3, DM4 and / or DM21. In certain embodiments, the third payload may be a duocarmycin. Suitable duocarmycins include duocarmycin A, duocarmycin Bl, duocarmycin B2, duocarmycin CI, duocarmycin C2, duocarmycin D, duocarmycin SA, duocarmycin MA, and CC- 1065. The term "duocarmycin" should be understood as referring also to synthetic analogs of duocarmycins, such as adozelesin, bizelesin, carzelesin, KW-2189 and CBI-TMI. In certain embodiments, third payload may be a NAMPT inhibitor. As used herein, the terms “NAMPT inhibitor” and “nicotinamide phosphoribosyl transferase inhibitor” refer to an inhibitor that reduces the activity of nicotinamide phosphoribosyl transferase (NAMPT). The term “NAMPT inhibitor” may also include prodrugs of a NAMPT inhibitor. Examples of NAMPT inhibitors include, without limitation, FK866 (also referred to as APO866), GPP 78 hydrochloride, ST 118804, STF31, pyridyl cyanoguanidine (also referred to as CH-828), GMX-1778, and P7C3. Additional NAMPT inhibitors are known in the art see, e.g., PCT Publication WO 2015 / 054060, U.S. Pat. Nos.8,211,912, and 9,676,721, which are incorporated by reference herein in their entireties. In some embodiments, the NAMPT inhibitor is FK866. In some embodiments, the NAMPT inhibitor is GMX-1778. In certain embodiments, the third payload may be a tubulysin. Tubulysins are cytotoxic peptides, which include 9 members (A-I). Tubulysin A has potential application as an anticancer agent. It arrests cells in the G2 / M phase. Tubulysin A inhibits polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules. Tubulysin A has potent cytostatic effects on various tumor cell lines with IC50 in the picomolar range. Other tubulysins that may be used in the method of the invention include tubulysin E. In certain embodiments, the third payload may be an enediyne. The term “enediyne,” as used herein, refers to a class of bacterial natural products characterized by either nine- and ten-membered rings containing two triple bonds separated by a double bond (see, e.g., K. C. Nicolaou; A. L. Smith; E. W. Yue (1993). “Chemistry and biology of natural and designed enediynes”. PNAS 90 (13): 5881-5888; the entire contents of which are incorporated herein by reference). Some enediynes are capable of undergoing Bergman cyclization, and the resulting diradical, a 1,4-dehydrobenzene derivative, is capable of abstracting hydrogen atoms from the sugar backbone of DNA which results in DNA strand cleavage (see, e.g., S. Walker; R. Landovitz; W. D. Ding; G. A. Ellestad; D. Kahne (1992). “Cleavage behavior of calicheamicin gamma 1 and calicheamicin T”. Proc Natl Acad Sci U.S.A.89 (10): 4608-12; the entire contents of which are incorporated herein by reference). Their reactivity with DNA confers an antibiotic character to many enediynes, and some enediynes are clinically investigated as anticancer antibiotics. Nonlimiting examples of enediynes are dynemicin, neocarzinostatin, calicheamicin, esperamicin (see, e.g., Adrian L. Smith and K. C. Bicolaou, “The Enediyne Antibiotics” J. Med. Chem., 1996, 39 (11), pp 2103-2117; and Donald Borders, “Enediyne antibiotics as antitumor agents,” Informa Healthcare; 1st edition (Nov. 23, 1994, ISBN-10: 0824789385; the entire contents of which are incorporated herein by reference). In a particular embodiment, the third payload may be calicheamicin. In certain embodiments, the third payload may be a doxorubicin. “Doxorubicin” as used herein refers to members of the family of Anthracyclines derived from Streptomycesbacterium Streptomyces peucetius var. caesius, and includes doxorubicin,daunorubicin, epirubicin and idarubicin. In certain embodiments, the third payload may be a kinesin spindle protein inhibitor. The term “kinesin spindle protein inhibitor” refers to a compound that inhibits the kinesin spindle protein, which involves in the assembly of the bipolar spindle during cell division. Examples of kinesin spindle protein inhibitors include ispinesib, SB715992 or SB743921 from GlaxoSmithKline and pentamidine / chlorpromarine from CombinatoRx. In certain embodiments, the third payload may a cryptophycin, or derivative thereof, as described in US20180078656A1, US 20210163458 A1, US20210228726A1, which are incorporated by reference. In certain embodiments, the third payload may be sandramycin. Sandramycin is adepsipeptide that has first been isolated from Nocardioides sp. (ATCC 39419) and hasbeen shown to have cytotoxic and anti-tumor activity. In certain embodiments, the third payload may be an antimetabolite or metabolite inhibitor. Exemplary antimetabolites and metabolite inhibitors are well known in the art and include pemetrexed or other folate antimetabolites. Pemetrexed is is known to inhibit three enzymes used in purine and pyrimidine synthesis: thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotideformyltransferase (GARFT). By inhibiting the formation of precursor purine andpyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells. In certain other embodiments, any other antimetabolite / metabolite inhibitor may be used that inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and / orglycinamide ribonucleotide formyltransferase (GARFT).In certain other embodiments, said antimetabolite / metabolite inhibitor is a thymidine synthase (or thymidylate synthase) inhibitor. Thymidylate synthase inhibitors are chemical agents which inhibit the enzyme thymidylate synthase and have potential as an anticancer chemotherapy. This inhibition prevents the methylation of C5 of deoxyuridine monophosphate (dUMP) thereby inhibiting the synthesis of deoxythymidine monophosphate (dTMP). The downstream effect is promotion of cell death because cells would not be able to properly undergo DNA synthesis if they are lacking dTMP, a necessary precursor to dTTP. Within the present invention, the thymidylate synthase inhibitor may be, without limitation, raltitrexed, pemetrexed, nolatrexed, ZD9331, GS7904L, fluorourcail, BGC-945 and OSI-7904L. In certain embodiments, the third payload may be an amatoxin. Amatoxins (including alpha-amanitin, beta-amanitin and amanitin) are cyclic peptides composed of 8 amino acids. They can be isolated from Amanita phalloides mushrooms or prepared from the building blocks by synthesis. Amatoxins inhibit specifically the DNA-dependent RNA polymerase II of mammalian cells, and by this transcription and protein biosynthesis of the cells affected. Inhibition of transcription in a cell causes stop of growth and proliferation. Though not covalently bound, the complex between amanitin and RNA- polymerase II is very tight (KD=3 nM). Dissociation of amanitin from the enzyme is a very slow process what makes recovery of an affected cell unlikely. When in a cell the inhibition of transcription will last too long, the cell undergoes programmed cell death (apoptosis). In one embodiment, term "Amatoxin" as used herein refers to an alpha- amanitin or variant thereof as described e.g., in WO2010 / 115630, WO2010 / 115629, WO2012 / 119787, WO2012 / 041504, and WO2014 / 135282. In certain embodiments, the third payload is a DNA damage repair inhibitor. Exemplary DNA repair inhibitors include PARP inhibitors, ATR / ATM inhibitors and Chk1 inhibitors. Further, as a DNA repair inhibitor, a kinase inhibitor may be used as a third payload. In one embodiment, the kinase inhibitor is a tyrosine kinase inhibitor. In certain embodiments, the third payload is a topoisomerase II inhibitor. Topoisomerase II inhibitors are well known in the art. In certain embodiments, the topoisomerase II inhibitor is selected from the group consisting of aminocoumarin (novobiocin), fluoro-quinolones (cinonaxin), derivative of epipodophyllotoxin (etoposide), acridine or anthraquinone derivatives (amsacrine, pixantrone). In certain embodiments, the ADC or linker of the invention comprises only one third payload. In other embodiments, the ADC or linker of the invention comprises multiple third payloads. In certain embodiments, the third payloads are identical in structure. In other embodiments, the third payloads are different in structure. While the number of third payloads is not limited, in certain embodiments, the ADC or linker of the invention consists of or comprises of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 third payload(s). As mentioned above, the invention relates, at least in part, to linker or to an antibody- payload conjugate comprising an antibody conjugated to a linker. As used herein, a “linker” generally refers to a molecule that connects two or more parts of a conjugate or construct. Linkers may also be referred to as spacers. It is to be understood that the present invention is based, at least in part, on the surprising finding that the combination of three different payloads—a cell-permeable topoisomerase I inhibitor, a cell-impermeable topoisomerase I inhibitor and a further cytotoxic molecule—results in potent anti-tumor activity. Therefore, the presentinvention is not limited to a specific conjugation strategy and any possible linker canbe used in accordance with the present invention. That is, a linker according to the invention may be conjugated to an antibody using various strategies, including non-specific conjugation methods such as lysine conjugation which employ NHS esters or isothiocyanates to react with amine groups on lysine residues of antibody, or cysteine conjugation which employ maleimides, iodoacetamides, or disulfide rebridging reagents to target thiol groups on cysteine residues of an antibody. Additionally or alternatively, site-specific conjugation strategies may be employed, such as enzymatic conjugation (e.g., transglutaminase, sortase), unnatural amino acid incorporation, or click chemistry for precise and homogeneous ADCs. In an exemplary embodiment, the linker is a peptide linker. A “peptide linker”, within the meaning of the present invention, is a molecule comprising at least two amino acid residues, wherein the two amino acid residues are coupled via a peptide bond. The peptide linker may be modified with one or more reactive groups to allow conjugation of the peptide linker to an antibody. For example, the peptide linker may be functionalized with a maleimide to allow conjugation to cysteine residues of an antibody. In certain embodiments, the peptide linker is a substrate for a microbial transglutaminase. In particular embodiments, it is envisioned that the peptide linker is suitable for conjugation to a glutamine residue comprised in an antibody. In such embodiments, the peptide linker comprises at least one amino acid residue comprising a primary amine. I certain embodiments, in the peptide linker according to the invention the primary amine comprised in the amino acid residue is a) a primary amine in a side chain of a lysine, a lysine derivative or a lysine mimetic; or b) a primary amine comprised in an N-terminal amino acid residue having the structure NH2-(Y)-COOH. In certain embodiments, the amino acid residue comprising the primary amine is a lysine residue. In such embodiments, the peptide linker comprises a peptide moiety comprising at least one lysine residue. However, the linker in accordance with the invention may also comprise a lysine mimetic or a lysine derivative, provided that the lysine mimetic or lysine derivative comprises a free primary amine in the amino acid side chain. In certain embodiments, the amino acid residue comprising the primary amine may be a lysine mimetic. The term “lysine mimetic”, as used herein, refers to a compound that has a structure different from lysine, but that has similar characteristics as lysine and may thus be used to replace lysine in a peptide or protein without significantly altering the function and / or structure of said peptide or protein. In certain embodiments, a lysine mimetic may differ from lysine in the length or composition of the aliphatic chain thatconnects the primary amine and the -carbon atom. Thus, in certain embodiments, thelysine mimetic may be ornithine, homolysine or 2,7-diaminoheptanoic acid. In certain embodiments, the lysine mimetic may be a beta-amino acid, such as beta-homolysine. In certain embodiments, the amino acid residue comprising the primary amine may be a lysine derivative. The term “lysine derivative”, as used herein, refers to a lysine or lysine mimetic, wherein one or more functional groups comprised in the lysine or lysine mimetic is (are) modified or substituted. In certain embodiments, the amino group in the side chain of the lysine derivative is unmodified, such that it is available for conjugation to a glutamine residue in a protein. Thus, in certain embodiments, the “lysine derivative” comprised in the peptide linker in accordance with the presentinvention comprises a modified or substituted -amino and / or -carboxyl group.In certain embodiments, the primary amine comprised in the amino acid residue may be a primary amine comprised in an N-terminal amino acid residue having the structure NH2-(Y)-COOH.In certain embodiments, the primary amine may be the -amino group of an -aminoacid. The -amino acid may be any proteinogenic -amino acid, including alanine,arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine and valine.In a particular embodiment, the primary amine may be the -amino group of a glycineresidue. In some embodiments, the glycine residue is the N-terminal amino acidresidue of the peptide linker, such that the -amino group is available for conjugationto a glutamine residue via a microbial transglutaminase. The amino acid comprising the primary amine may be a non-canonical or a synthetic amino acid. A “non-canonical amino acid”, as used herein, may be any amino acid that is not part of the set of proteinogenic amino acids, but that can be obtained from a natural source. However, it has to be noted that some non-canonical amino acids may also be found in naturally occurring peptides and / or proteins. A “synthetic amino acid”, as used herein, may be any molecule that falls under the general definition of an amino acid (NH2-(Y)-COOH), i.e., that comprises an amino group and a carboxyl group, but that is not found in nature. Thus, non-natural amino acids are preferably obtained by chemical synthesis. It is to be understood that the differentiation between a non- canonical amino acid and a synthetic amino acid may be uncertain in some instances. For example, an amino acid that is defined as a synthetic amino acid may be, at a later time point, identified in nature and thus reclassified as a non-canonical amino acid. The non-canonical or synthetic amino acid may be an -, -, -, -, or -amino acid.In certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH. In certain embodiments, the moiety Y may comprise a carbon comprising framework of 1 to 200 atoms, optionally a carbon comprising framework of at least 10 atoms, e.g., 10 to 100 atoms or 20 to 100 atoms, substituted at one or more atoms, optionally wherein the carbon comprising framework is a linear hydrocarbon or comprises a cyclic group, a symmetrically or asymmetrically branched hydrocarbon, monosaccharide, disaccharide, linear or branched oligosaccharide (asymmetrically branched or symmetrically branched), other natural linear or branched oligomers (asymmetrically branched or symmetrically branched), or more generally any dimer, trimer, or higher oligomer (linear, asymmetrically branched or symmetrically branched) resulting from any chain-growth or step-growth polymerization process. Y may further be any straight, branched and / or cyclic C2-30alkyl, C2-30alkenyl, C2-30alkynyl, C2-30heteroalkyl, C2-30heteroalkenyl, C2-30heteroalkynyl, optionally wherein one or more homocyclic aromatic compound radical or heterocyclic compound radical may be inserted; notably, any straight or branched C2-5alkyl, C5-10alkyl, C11-20alkyl, - O-C1-5alkyl, -O-C5-10alkyl, -O-C11-20alkyl, or (CH2-CH2-O-)1-24or (CH2)x1-(CH2-O- CH2)1-24-(CH2)x2- group, wherein x1 and x2 are independently an integer selected among the range of 0 to 20, an amino acid, an oligopeptide, glycan, sulfate, phosphate, or carboxylate. In some embodiments, Y may comprise a C2-6alkyl group. In a particular embodiment, in the peptide linker according to the invention, Y is -(R2C)n- and wherein n is an integer ranging from 1 to 20, from 1 to 15, from 1 to 10. That is, Y may have the structure In certain embodiments, Y may be a substituted or unsubstituted alkyl or alkenyl chain. When Y is a substituted or unsubstituted alkenyl chain, it is to be understood that at least two R moieties attached to consecutive carbon molecules have to be absent. The term "substituted alkyl", as used herein, generally refers to an alkyl group with an additional group or groups attached to any carbon of the alkyl group. That is, the substituted alkyl may comprise the structure -(R2C)n-, wherein each R may independently be a hydrogen or a functional group such as an alkyl, lower alkyl, aryl, acyl, halogen, alkylhalo, hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy, aryloxy, aryloxyalkyl, mercapto, both saturated and unsaturated cyclic hydrocarbon, heterocycle, and other organic group. In certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(R2C)n- and wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In certain embodiments, at least 1, 2, 3, 4 or 5 moieties R comprised in the structure -(R2C)n- may be a functional group such as an alkyl, lower alkyl, aryl, acyl, halogen, alkylhalo, hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy, aryloxy, aryloxyalkyl, mercapto, both saturated and unsaturated cyclic hydrocarbon, heterocycle, and other organic group. In a particular embodiment, in the peptide linker according to the invention, the at least one R moiety of each -(R2C)- monomer is hydrogen. That is, in certain embodiments, one R moiety of each -(R2C)- monomer may be a hydrogen, while the other R moiety may be a functional group such as an alkyl, lower alkyl, aryl, acyl, halogen, alkylhalo, hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy, aryloxy, aryloxyalkyl, mercapto, both saturated and unsaturated cyclic hydrocarbon, heterocycle, and other organic group. Alternatively, one R moiety of each -(R2C)- monomer may be hydrogen and the other R moiety may be absent (in case of alkenes). In certain embodiments, some -(R2C)- monomers comprised in a moiety Y may comprise two hydrogen substituents and some -(R2C)- monomers comprised in the same moiety Y may comprise one hydrogen substituent and one substituent R as defined herein. In a particular embodiment, in the peptide linker according to the invention, both R moieties of each -(R2C)- monomer are hydrogen.In certain embodiments the structure -(R2C)n- may be an unsubstituted alkyl chainwherein all moieties R comprised in the structure -(R2C)n- are hydrogen atoms. Thatis, in certain embodiments, the structure -(R2C)n- may be a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl group. That is, in certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 20. In certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 15. in a certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 10. in certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 9. in certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 8. in certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 7. in certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(Y)-COOH, wherein Y is -(CH2)n- and wherein n is an integer from 1 to 6. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 1. That is, in certain embodiments, the amino acid comprising the primary amine may be glycine. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 2. That is, incertain embodiments, the amino acid comprising the primary amine may be -alanine.In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 3. That is, in certain embodiments, the amino acid comprising the primary amine may be 4- aminobutyric acid. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 4. That is, in certain embodiments, the amino acid comprising the primary amine may be 5- aminopentanoic acid. (Exemplary linker containing 5-aminopentanoic acid is shown in FIG.24) In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 5. That is, in certain embodiments, the amino acid comprising the primary amine may be 6- aminohexanoic acid. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 6. That is, in certain embodiments, the amino acid comprising the primary amine may be 7- aminoheptanoic acid. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 7. That is, in certain embodiments, the amino acid comprising the primary amine may be 8- aminooctanoic acid. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 8. That is, in certain embodiments, the amino acid comprising the primary amine may be 9- aminononanoic acid. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 9. That is, in certain embodiments, the amino acid comprising the primary amine may be 10- aminodecanoic acid. In certain embodiments, Y may have the structure -(CH2)n-, wherein n is 10. That is, in certain embodiments, the amino acid comprising the primary amine may be 11- aminoundecanoic acid. In certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(CH2)n-X-(CH2)n-COOH, wherein X is a substituted or unsubstituted alkyl or heteroalkyl chain and wherein n is an integer from 0-20, from 0-10 or from 0-6. That is, in certain embodiments, the amino acid comprising the primary amine may have the structure NH2-(CH2)n-X-COOH, wherein X is a substituted or unsubstituted alkyl or heteroalkyl chain and wherein n is an integer from 1-20, from 1-10 or from 1- 6. In certain embodiments, the amino acid comprising the primary amine may have the structure NH2-X-(CH2)n-COOH, wherein X is a substituted or unsubstituted alkyl or heteroalkyl chain and wherein n is an integer from 1-20, from 1-10 or from 1-6. In one embodiment, the amino acid comprising the primary amine comprises at least one methylene group (CH2). For example, the at least one methylene group may be directly coupled to the primary amine. That is, the amino acid comprising the primary amine may comprise the structure NH2-CH2-. In one embodiment, in a peptide linker according to the invention, the primary amine comprised in the amino acid residue is a) a primary amine in a side chain of a lysine, a lysine derivative or a lysine mimetic; or b) a primary amine comprised in an N-terminal amino acid residue having the structure NH2-(CH2)n-COOH, wherein n is an integer ranging from 1 to 10. In certain embodiments, a payload is directly or indirectly attached to the N-terminal end of the peptide linker. In such embodiments, it is preferred that the primary amine comprised in the amino acid residue is a primary amine in a side chain of a lysine, a lysine derivative or a lysine mimetic; more preferably a primary amine in a side chain of a lysine residue. In a particular embodiment, in the peptide linker according to the invention, the linker comprises not more than 25, 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4 amino acid residues. The peptide linker in accordance with the present invention may comprise at least two amino acid residues and not more than 25 amino acid residues. In some embodiments, all amino acid residues comprised in the peptide linker according to the invention form a single peptide. However, it is to be understood that the peptide linker may comprise two or more peptide moieties. For example, in certain embodiments, the peptide linker may comprise two peptide moieties, wherein the two peptide moieties are connected to each other covalently, but not by a peptide bond. Examples of such peptide linkers will be given further below. In a particular embodiment, in the peptide linker in accordance with the present invention, the net charge of the linker is neutral or positive. The net charge of a peptide is usually calculated at neutral pH (7.0). In the simplest approach, the net charge is determined by adding the number of positively charged amino acid residues (Arg, Lys and His) and the number of negatively charged ones (Asp and Glu) and calculate the difference of the two groups. In cases where the linker comprises non-canonical amino acids or amino acid derivatives comprising a charged functional group, the skilled person is capable of calculating the net charge at neutral pH accordingly. In certain embodiments, the payloads may also contribute to the net charge of the linker. However, the skilled person is aware of methods to calculate the net charge of the entire linker, including any payloads, preferably at neutral pH (7.0). In certain embodiments, the net charge of a peptide linker is calculated solely based on the amino acid residues comprised in the linker, including amino acid mimetics and amino acid derivatives. Thus, in a particular embodiment, in the peptide linker in accordance with the present invention, the net charge of the amino acid residues comprised in the peptide linker is neutral or positive. In a particular embodiment, in the peptide linker in accordance with the present invention, the linker comprises no negatively-charged amino acid residues. That is, the linker may be free of negatively charged amino acid residues, including negatively-charged amino acid mimetics and amino acid derivatives. A negatively charged amino acid residue is an amino acid, amino acid mimetic or amino acid derivative which carries a negative charge at neutral pH (7.0). Negatively charged canonical amino acids are glutamic acid and aspartic acid. However, negatively charged non-canonical amino acids, amino acid mimetics and amino acid derivatives are known in the art. It has to be noted that the peptide linker in accordance with the present invention may comprise one or more glutamate or aspartate residue. However, in such embodiments, it is preferred that the carboxyl group comprised in the aspartate or glutamate side chain is coupled to a payload. In a particular embodiment, in the peptide linker in accordance with the present invention, the linker comprises at least one positively-charged amino acid residue. In certain embodiments, the peptide linker comprises a positively charged lysine residue, which provides the primary amine for the transglutaminase-mediated conjugation to an antibody. However, it is preferred herein that the peptide linker comprises at least one additional positively charged amino acid. The additional positively charged amino acid may be a canonical amino acid residue, such as arginine or histidine. However, the additional positively charged amino acid may also be a non- canonical amino acid. In a particular embodiment, in the peptide linker in accordance with the present invention, the linker comprises at least one arginine residue. It has been demonstrated herein that linkers comprising an arginine residue can be conjugated to glycosylated antibodies with high efficiency. Thus, in certain embodiments a peptide linker in accordance with the present invention comprises at least one arginine residue. It is to be noted that the arginine residue may also be replaced by an arginine mimetic or arginine derivative. The arginine residue may be located at any position of the peptide linker. In certain embodiments, the arginine residue is adjacent to the amino acid residue comprising the primary amine. In certain embodiments, the arginine residue is coupled to the N- terminus of the amino acid comprising the primary amine, i.e., a lysine residue, a lysine mimetic or a lysine derivative (e.g., RK motif). In certain embodiments, the arginine residue is coupled to the C-terminus of the amino acid comprising the primary amine, i.e., a lysine residue, a lysine mimetic or a lysine derivative (e.g., KR motif). In certain embodiments, the arginine residue is coupled to the amino acid comprising the primary amine, i.e., a lysine residue, a lysine mimetic or a lysine derivative, via another amino acid residue, preferably an alanine residue (KAR or RAK motif). In certain embodiments, the peptide linker comprises an arginine and a histidine residue. It has been demonstrated in WO 2023 / 161291, which is incorporated herein in its entirety, that linkers comprising a histidine residue can be conjugated to glycosylated antibodies with high efficiency. Thus, in a particular embodiment, the peptide linker according to the invention comprises at least one histidine residue. It is to be noted that the histidine residue may also be replaced by a histidine mimetic or histidine derivative. The histidine residue may be located at any position of the peptide linker. In certain embodiments, the histidine residue is adjacent to the amino acid residue comprising the primary amine. In certain embodiments, the histidine residue is coupled to the N- terminus of the amino acid comprising the primary amine, i.e., a lysine residue, a lysine mimetic or a lysine derivative (e.g., HK motif). In certain embodiments, the histidine residue is coupled to the C-terminus of the amino acid comprising the primary amine, i.e., a lysine residue, a lysine mimetic or a lysine derivative (e.g., KH motif). In certain embodiments, the histidine residue is coupled to the amino acid comprising the primary amine, i.e., a lysine residue, a lysine mimetic or a lysine derivative, via another amino acid residue, preferably an alanine residue (KAH or HAK motif). In certain embodiments, the peptide linker comprises a histidine and an arginine residue. In a particular embodiment, in the peptide linker in accordance with the present invention, the linker comprises the sequence motif RK. Peptide linkers comprising the sequence motif RK (argynyl-lysyl) can be conjugated to glycosylated antibodies with exceptionally high efficiency, even if the linker comprises two or more payloads. It is to be understood that the lysine residue comprised in the RK motif contains the primary amine via which the peptide linker is conjugated to a glutamine residue comprised in the antibody. That is, the lysine residue comprised in the RK motif is preferably the amino acid comprising the primary amine. In certain embodiments, the motif RK consists of the amino acids arginine and lysine. However, it is to be understood that the arginine and / or the lysine residue may be substituted with an arginine mimetic / derivative and / or a lysine mimetic / derivative. That is, in certain embodiments, the motif RK may comprise an arginine mimetic. The term “arginine mimetic”, as used herein, refers to a compound that has a structure that is different from arginine, but that has similar characteristics as arginine and may thus be used to replace arginine in a peptide or protein without significantly altering the function and / or structure of said peptide or protein. An arginine mimetic may differ from arginine in length or composition of the aliphatic chain that connects the guanidinogroup and the -carbon atom. Alternatively, or in addition, arginine mimetics may differfrom arginine in the guanidino group itself. That is, the arginine mimetic may comprise a functional group with similar physicochemical properties as the guanidino group. In certain embodiments, the arginine mimetic may be homoarginine, 2-amino-3-guanidino-propionic acid, -ureidoalanine or citrulline.In certain embodiments, the motif RK may comprise an arginine derivative. The term “arginine derivative”, as used herein, refers to an arginine or arginine mimetic, wherein one or more functional groups comprised in the arginine or arginine mimetic is (are) modified or substituted. An arginine derivative may be arginine or an arginine mimetic, wherein the guanidino group is substituted or modified. In certain embodiments, thearginine derivative may be -methylarginine. In embodiments, where the residue R islocated in the N-terminal position of the linker, R may be an arginine derivative whereinthe -amino group is modified or substituted. In certain embodiments the -aminogroup of the arginine or arginine mimetic may be acetylated. In certain embodiments, the motif RK may comprise a lysine mimetic or lysine derivative as defined elsewhere herein. In certain embodiments, the motif RK may comprise a lysine mimetic / derivative and an arginine mimetic / derivative. In certain embodiments, the lysine residue, or the lysine mimetic or lysine derivative, may be separated from the arginine residue, or the arginine mimetic or arginine derivative, by one amino acid residue. That is, the peptide linker of the invention may comprise the sequence motif RXK or KXR, wherein X may be any amino acid. In a preferred embodiment, the lysine residue, or the lysine mimetic or lysine derivative, may be separated from the arginine residue, or the arginine mimetic or arginine derivative, by an alanine residue. That is, the peptide linker of the invention may comprise the sequence motif RAK or KAR. It has been demonstrated in WO 2023 / 161291, which is incorporated herein in its entirety, that a linker comprising the sequence motif KAR can be conjugated to glycosylated antibodies with exceptionally high conjugation efficiency. In a particular embodiment, in the peptide linker in accordance with the present invention, the linker comprises the sequence motif HK. Peptide linkers comprising the sequence motif HK (histidyl-lysyl) can be conjugated to glycosylated antibodies with very high efficiency, even if the linker comprises two or more payloads. It is to be understood that the lysine residue comprised in the HK motif contains the primary amine via which the peptide linker is conjugated to a glutamine residue comprised in the antibody. That is, the lysine residue comprised in the HK motif is preferably the amino acid comprising the primary amine. In exemplary embodiments, the motif HK consists of the amino acids histidine and lysine. However, it is to be understood that the histidine and / or the lysine residue may be substituted with a histidine mimetic / derivative and / or a lysine mimetic / derivative. That is, in certain embodiments, the motif HK may comprise a histidine mimetic. The term “histidine mimetic”, as used herein, refers to a compound that has a structure that is different from histidine, but that has similar characteristics as histidine and may thus be used to replace histidine in a peptide or protein without significantly altering the function and / or structure of said peptide or protein. A histidine mimetic may differ from histidine in length or composition of the aliphatic chain that connects the imidazolegroup and the -carbon atom. Alternatively, or in addition, histidine mimetics may differfrom histidine in the imidazole group itself. That is, the histidine mimetic may comprise a functional group with similar physicochemical properties as the imidazole group. In certain embodiments, the histidine mimetic may be homohistidine. In certain embodiments, the motif HK may comprise a histidine derivative. The term “histidine derivative”, as used herein, refers to a histidine or histidine mimetic, wherein one or more functional groups comprised in the histidine or histidine mimetic is (are) modified or substituted. A histidine derivative may be histidine or a histidine mimetic, wherein the imidazole group is substituted or modified. In embodiments, where the residue H is located in the N-terminal position of the linker, H may be a histidinederivative wherein the -amino group is modified or substituted. In certainembodiments the -amino group of the histidine or histidine mimetic may beacetylated. In certain embodiments, the motif HK may comprise a lysine mimetic or lysine derivative as defined elsewhere herein. In certain embodiments, the motif HK may comprise a lysine mimetic / derivative and a histidine mimetic / derivative. In certain embodiments, the lysine residue, or the lysine mimetic or lysine derivative, may be separated from the arginine residue, or the arginine mimetic or arginine derivative, by one amino acid residue. That is, the peptide linker of the invention may comprise the sequence motif HXK or KXH, wherein X may be any amino acid. In a preferred embodiment, the lysine residue, or the lysine mimetic or lysine derivative, may be separated from the arginine residue, or the arginine mimetic or arginine derivative, by an alanine residue. That is, the peptide linker of the invention may comprise the sequence motif HAK or KAH. In a particular embodiment, the peptide linker comprises any one of the amino acid sequences set forth in SEQ ID NO:1 – 29 or 82 - 93. In certain embodiments, the peptide linker may comprise the peptide sequence RKAA (SEQ ID NO:1). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide RKAA. In certain embodiments, the peptide linker may comprise the peptide sequence RK. Alinker comprising the sequence RK is shown herein (see Figure 8). In certainembodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide RK. In certain embodiments, the peptide linker may comprise the peptide sequence ARK (SEQ ID NO:2). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide ARK. In certain embodiments, the peptide linker may comprise the peptide sequenceRKARA (SEQ ID NO:3). In certain embodiments, one or more payloads are attachedto the N- and / or C-terminus of the peptide RKARA. In certain embodiments, the peptide linker may comprise the peptide sequenceRKAAAA (SEQ ID NO:4). In certain embodiments, one or more payloads are attachedto the N- and / or C-terminus of the peptide RKAAAA. In certain embodiments, the peptide linker may comprise the peptide sequenceRKAAAAAA (SEQ ID NO:5). In certain embodiments, one or more payloads areattached to the N- and / or C-terminus of the peptide RKAAAAAA. In certain embodiments, the peptide linker may comprise the peptide sequenceRKAASGSG (SEQ ID NO:6). In certain embodiments, one or more payloads areattached to the N- and / or C-terminus of the peptide RKAASGSG. In certain embodiments, the peptide linker may comprise the peptide sequence RKHA (SEQ ID NO:7). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide RKHA. In certain embodiments, the peptide linker may comprise the peptide sequence RKHAAA (SEQ ID NO:8). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide RKHAAA. In certain embodiments, the peptide linker may comprise the peptide sequence GGR (SEQ ID NO:9). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide GGR. In certain embodiments, the peptide linker may comprise the peptide sequence GGRG (SEQ ID NO:10). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide GGRG. In certain embodiments, the peptide linker may comprise the peptide sequence EARKAA (SEQ ID NO:11). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide EARKAA. In addition, it is envisioned that one or more payloads may be attached to the side chain of the glutamate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the glutamate residue, the peptide sequence of the linker may also be viewed as QARKAA (SEQ ID NO:84). In certain embodiments, the peptide linker may comprise the peptide sequence RKAEA (SEQ ID NO:12). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide RKAEA. In certain embodiments, the one or more payloads are attached to the side chain of the glutamate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the glutamate residue, the peptide sequence of the linker may also be viewed as RKAQA (SEQ ID NO:85). In certain embodiments, the peptide linker may comprise the peptide sequence HKA (SEQ ID NO:13). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide HKA. In certain embodiments, the peptide linker may comprise the peptide sequence RhKAA(SEQ ID NO:14), wherein hK is homolysine. In certain embodiments, one or morepayloads are attached to the N- and / or C-terminus of the peptide RhKAA. In certain embodiments, the peptide linker may comprise the peptide sequence XGRG(SEQ ID NO:15), wherein X has the structure NH2-(CH2)n-COOH, wherein n is aninteger from 1-20, preferably from 1-10. A linker comprising the sequence XGRG is exemplified in FIG.24. In certain embodiments, one or more payloads are attached to the C-terminus of the peptide XGRG. In certain embodiments, the peptide linker may comprise the peptide sequence RKVCit(SEQ ID NO:16), wherein Cit is citrulline. In certain embodiments, one or morepayloads are attached to the N- and / or C-terminus of the peptide RKVCit. In certain embodiments, the peptide linker may comprise the peptide sequence RKAR (SEQ ID NO:17). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide RKAR. In certain embodiments, the peptide linker may comprise the peptide sequence RKVA(SEQ ID NO:18). In certain embodiments, one or more payloads are attached to theN- and / or C-terminus of the peptide RKVA. In certain embodiments, the peptide linker may comprise the peptide sequence KAR(SEQ ID NO:19). In certain embodiments one or more payloads are attached to the N-and / or C-terminus of the peptide KAR. In certain embodiments, the peptide linker may comprise the peptide sequenceRKEAA (SEQ ID NO:20). In certain embodiments, one or more payloads are attachedto the N- and / or C-terminus of the peptide RKEAA. In addition, it is preferred that one or more payloads are attached to the side chain of the glutamate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the glutamate residue, the peptide sequence of the linker may also be viewed as RKQAA (SEQ ID NO:86). In certain embodiments, the peptide linker may comprise the peptide sequence RKDA(SEQ ID NO:82). In certain embodiments, one or more payloads are attached to theN- and / or C-terminus of the peptide RKDA. In certain embodiments, one or more payloads are attached to the side chain of the aspartate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the aspartate residue, the peptide sequence of the linker may also be viewed as RKNA (SEQ ID NO:83). In certain embodiments, the peptide linker may comprise the peptide sequence ERKAA (SEQ ID NO:21). In certain embodiments, one or more payloads are attached to the N- and / or C-terminus of the peptide ERKAA. In addition, it is preferred that one or more payloads are attached to the side chain of the glutamate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the glutamate residue, the peptide sequence of the linker may also be viewed as QRKAA (SEQ ID NO:87). In certain embodiments, the peptide linker may comprise the peptide sequence RKAH(SEQ ID NO:22). In certain embodiments, one or more payloads are attached to theN- and / or C-terminus of the peptide RKAH. In certain embodiments, the peptide linker may comprise the peptide sequence RKAN(SEQ ID NO:23). In certain embodiments,, one or more payloads are attached to theN- and / or C-terminus of the peptide RKAN. In certain embodiments, the peptide linker may comprise the peptide sequenceRKGGFG (SEQ ID NO:24). In certain embodiments, one or more payloads areattached to the N- and / or C-terminus of the peptide RKGGFG. In certain embodiments, the peptide linker may comprise the peptide sequence RKGP(SEQ ID NO:25). In certain embodiments, one or more payloads are attached to theN- and / or C-terminus of the peptide RKGP. In certain embodiments, the peptide linker may comprise the peptide sequenceKRKAA (SEQ ID NO:26). In certain embodiments, one or more payloads are attachedto the N- and / or C-terminus of the peptide KRKAA. In addition, one or more payloads may be attached to the side chain of one of the lysine residues, e.g., the N-terminal lysine residue. In certain embodiments, the peptide linker may comprise the peptide sequenceSRKAA (SEQ ID NO:27). In certain embodiments, one or more payloads are attachedto the N- and / or C-terminus of the peptide SRKAA. In addition, one or more payloads may be attached to the side chain of the serine residue. In certain embodiments, the peptide linker may comprise the peptide sequenceDDRKAA (SEQ ID NO:28). In certain embodiments, one or more payloads areattached to the N- and / or C-terminus of the peptide DDRKAA. In addition, one or more payloads may be attached to the side chains of the aspartate residues. It is to be understood that when an amine comprising payload is attached to a side chain of an aspartate residue, the peptide sequence of the linker may also be viewed as DNRKAA (SEQ ID NO:88), NDRKAA (SEQ ID NO:89) or NNRKAA (SEQ ID NO:90). In certain embodiments, the peptide linker may comprise the peptide sequenceEERKValCit (SEQ ID NO:29). In certain embodiments, one or more payloads areattached to the N- and / or C-terminus of the peptide EERKValCit. In addition, one or more payloads may be attached to the side chains of the glutamate residues. It is to be understood that when an amine comprising payload is attached to a side chain of a glutamate residue, the peptide sequence of the linker may also be viewed as EQRKValCit (SEQ ID NO:91), QERKValCit (SEQ ID NO:92) or QQRKValCit (SEQ ID NO:93). In certain embodiments, the peptide linker may comprise the peptide sequenceRKDAR (SEQ ID NO:143). In certain embodiments, one or more payloads are attachedto the N- and / or C-terminus of the peptide RKDAR. In addition, one or more payloads may be attached to the side chain of the aspartate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the aspartate residue, the peptide sequence of the linker may also be viewed as RKNAR (SEQ ID NO:144). In certain embodiments, the peptide linker may comprise the peptide sequence DRK. In certain embodiments, one or more payloads are attached to the N- and / or C- terminus of the peptide DRK. In addition, one or more payloads may be attached to the side chain of the aspartate residue. It is to be understood that when an amine comprising payload is attached to the side chain of the aspartate residue, the peptide sequence of the linker may also be viewed as NRK.In certain embodiments, the peptide linker is the linker shown in Figure 8.The peptide linker in accordance of the present invention may be used for the generation of antibody-payload conjugates having a payload-to-antibody ratio of 6 or higher by means of a microbial transglutaminase. Native glycosylated antibodies have a single conjugation site at glutamine residue 295 (Q295) of the heavy chain. Since most antibodies comprise two heavy chains, conjugating a linker with three payloads to each of the glutamine residues results in an antibody-payload conjugate comprising 6 payloads. Analogously, conjugating a linker with four payloads to each of the glutamine residues results in an antibody-payload conjugate comprising 8 payloads. Thus, in certain embodiments, the peptide linker according to the invention comprises 3 or 4 payloads. The inventors identified different ways to couple three or more payloads to a peptide linker. In certain embodiments, two payloads may be coupled to the C-terminal end of a peptide linker. In other embodiments two payloads may be coupled to the N-terminal end of a peptide linker. In yet another embodiment, one or two payloads may be coupled each to the N-terminal end of a peptide linker and to the C-terminal end of a peptide linker. In embodiments where no payload is attached to the N- or C-terminus of a peptide linker, it is preferred that the respective terminus is modified. That is, the N-terminus of a peptide linker may be acetylated and the C-terminus of a peptide linker may be amidated. In addition to coupling payloads to the terminal ends of a peptide linker, one or more payloads may also be coupled to amino acid side chains. The skilled person is aware of amino acid residues having functional groups in their amino acid side chains that allow for coupling of a payload. Amino acids having functional groups in their sidechains include, but are not limited to, those described by deGruiter et al inBiochemistry 2017, 56, 30, 3863–3873. Additionally, payloads may also be coupled tothe side chain of non-canonical amino acids, including but not limited to pAcF, CpK, pAMF, SCpHK, AzK, Sec. That is, in a particular embodiment, in the peptide linker in accordance with the present invention, the at least one payload is attached to a side chain of a glutamate, aspartate, tryptophan, cysteine, lysine, tyrosine, serine or threonine residue comprised in the peptide linker. In a particular embodiment, one or two payloads may be attached to the carboxylic acid of a glutamate or aspartate side chain. In a particular embodiment, one or two payloads may be attached to the amine of a lysine side chain. In a particular embodiment, one or two payloads may be attached to the thiol of a cysteine side chain. In a particular embodiment, one or two payloads may be attached to the hydroxyl of a serine, threonine, or tyrosine side chain. The payloads may be directly coupled to the peptide linker. For example, an amine- comprising payload may be coupled to the C-terminal end of a peptide linker via an isopeptide bond. Similarly, a carboxyl-comprising payload may be coupled to the N- terminal end of a peptide linker via an isopeptide bond or a thiol-comprising payload may be coupled to the side chain of a cysteine residue comprised in the peptide linker. In certain embodiments the payloads are coupled to the peptide linker via a chemical linker. In particular when two payloads are to be attached either to the N-terminal end or the C-terminal end of the peptide linker, the use of a chemical linker between the two payloads and the N- or C-terminal end is preferred. Accordingly, in a particular embodiment, at least one of the three or more payloads is attached to the peptide linker via a chemical linker. Within the present invention, at least one of the three or more payloads may be coupled to the peptide linker via a chemical linker. In certain embodiments, all payloads are coupled to the peptide linker via a chemical linker. A chemical linker can have various purposes. In certain embodiments, the chemical linker merely functions as an “adapter” to couple one payload to a peptide linker. For example, a chemical linker comprising an amine group may be used for coupling a payload to the C-terminal end of a peptide linker via an amide bond. In such embodiments, it is preferred that the chemical linker comprises one or more functional groups other than the amine to allow coupling of the payloads to the chemical linker via these additional functional groups. In certain embodiments, the chemical linker functions as an “amplifier moiety” to couple several payloads to a peptide linker. For example, a chemical linker comprising a disubstituted amine may be used as a dendron to attach two payloads. The disubstituted amine can serve as a branching point, allowing for the attachment of multiple payload molecules, thereby increasing the drug-to-antibody ratio (DAR). The chemical linker comprising the disubstituted amine may have the following structure: [payload]-NH-[payload] wherein each [payload] is directly or indirectly linked to the nitrogen (N). The disubstituted amine may be linked to a carboxyl group comprised in the linker via an amide bond. Preferably, the disubstituted amine is linked to the C-terminal end of the peptide linker or to the N-terminal end of the peptide linker via a dicarboxylic acid as described elsewhere herein. Examples of amplifiers comprising a disubstituted amine are the N-(2-Carboxyethyl)-Alanine (CEA) moiety and the piperidinedicarboxylic acid (PDCA)..An example of an amplifier comprising a CEA moiety is illustrated in Figure 8.Another example of an amplifier is the 2,6-bis-(hydroxymethyl)-p-cresol moiety. For example, a chemical linker comprising a disubstituted carboxylic acid may be used as a dendron to attach two payloads. Additional strategies for coupling two or more payloads to a peptide linker are disclosed in WO 2023 / 161291, which is incorporated herein in its entirety. Similarly, chemical linkers comprising a carboxyl group may be used for coupling one or more payload to the N-terminal end of a peptide linker via an amide bond. For example, a dicarboxylic acid molecule may be used for coupling an amine-comprising payload to the N-terminal end of a peptide. Further, chemical linkers comprising a compatible functional group may be used for coupling a payload to an amino acid side chain comprising in a peptide linker. In any of the embodiments disclosed above, the skilled person is capable of identifying a chemical linker that is suitable for coupling a payload to a peptide linker, whether thechemical serves as an “adapter” or an “amplifier moiety”. That is, the skilled person isable to identify a linker having the functional groups that are required for coupling a payload of interest to a functional group comprised in the peptide linker. However, the chemical linker may not only function as an adapter between the payload(s) and the peptide linker, but also fulfill other functions. That is, in certain embodiments, the chemical linker is an enzymatically and / or chemically cleavable linker. The cleavable linker may be any enzymatically and / or chemically cleavable linkerknown in the art, including, but not limited to, those described by Bargh et al (Chem.Soc. Rev., 2019, 48, 4361), which is fully incorporated herein by reference. Cleavable linkers have the advantage that the release of the payloads from the antibody can be controlled and / or facilitated. For example, one or more payloads may be coupled to the peptide linker via an enzymatically and / or chemically cleavable chemical linker.In certain embodiments, the chemical linker is cleavable in vivo. Cleavable linkers mayinclude chemically or enzymatically unstable or degradable linkages. Cleavable linkers generally rely on biological processes to liberate the payload, such as reduction in the cytoplasm, exposure to acidic conditions in the lysosome, or cleavage by specific proteases or other enzymes within, or outside, the cell. Cleavable linkers generally incorporate one or more chemical bonds that are either chemically or enzymatically cleavable. In certain embodiments, a linker comprises a chemically labile group such as hydrazone and / or disulfide groups. Linkers comprising chemically labile groups exploit differential properties between the plasma and some cytoplasmic compartments. The intracellular conditions to facilitate payload release for hydrazone containing linkers are the acidic environment of endosomes and lysosomes, while the disulfide containing linkers are reduced in the cytosol, which contains high thiol concentrations, e.g., glutathione. In certain embodiments, the plasma stability of a linker comprising a chemically labile group may be increased by introducing steric hindrance using substituents near the chemically labile group. Acid-labile groups, such as hydrazone or carbonate, remain intact during systemic circulation in the blood’s neutral pH environment (pH 7.3-7.5) and undergo hydrolysis and release the payload once the ADC is internalized into mildly acidic endosomal (pH 5.0-6.5) and lysosomal (pH 4.5-5.0) compartments of the cell. This pH dependent release mechanism has been associated with nonspecific release of the payload. To increase the stability of the hydrazone group of the linker, the linker may be varied by chemical modification, e.g., substitution, allowing tuning to achieve more efficient release in the lysosome with a minimized loss in circulation. Hydrazone- or carbonate- containing linkers may contain additional cleavage sites, such as additional acid-labile cleavage sites and / or enzymatically labile cleavage sites. Other acid-labile groups that may be included in chemical linkers include cis-aconityl- containing linkers. Cis-Aconityl chemistry uses a carboxylic acid juxtaposed to an amide bond to accelerate amide hydrolysis under acidic conditions. Cleavable chemical linkers may also include a disulfide group. Disulfides are thermodynamically stable at physiological pH and are designed to release the payload upon internalization inside cells, wherein the cytosol provides a significantly more reducing environment compared to the extracellular environment. Scission of disulfide bonds generally requires the presence of a cytoplasmic thiol cofactor, such as (reduced) glutathione (GSH), such that disulfide-containing linkers are reasonably stable in circulation, selectively releasing the payload in the cytosol. The intracellular enzyme protein disulfide isomerase, or similar enzymes capable of cleaving disulfide bonds, may also contribute to the preferential cleavage of disulfide bonds inside cells. GSH is reported to be present in cells in the concentration range of 0.5-10 mM compared with a significantly lower concentration of GSH or cysteine, the mostabundant low-molecular weight thiol, in circulation at approximately 5 M. Tumor cells,where irregular blood flow leads to a hypoxic state, result in enhanced activity of reductive enzymes and therefore even higher glutathione concentrations. In certain embodiments, the in vivo stability of a disulfide-containing linker may be enhanced by chemical modification of the linker, e.g., use of steric hinderance adjacent to the disulfide bond. Another type of cleavable linker that may be used is a chemical linker that is specifically cleaved by an enzyme. Such linkers are typically peptide-based or include peptidic regions that act as substrates for enzymes. Peptide based linkers tend to be more stable in plasma and extracellular milieu than chemically labile linkers. Peptide bonds generally have good serum stability, as lysosomal proteolytic enzymes have very low activity in blood due to endogenous inhibitors and the unfavorably high pH value of blood compared to lysosomes. Release of a payload from an antibody occurs specifically due to the action of lysosomal proteases, e.g., cathepsin, legumain, and plasmin. These lysosomal proteases may be present at elevated levels within certain tumor cells, but can also be found extracellularly, in the tumor microenvironment. Peptide-based linkers could also be cleaved by non-lysosomal extracellular proteases such as matrix metalloproteinases. Non-peptide-based linkers could also be specifically cleaved by glycosidases. In exemplary embodiments, the cleavable peptide is selected from tetrapeptides such as Gly-Phe-Leu-Gly (SEQ ID NO:30), Ala-Leu-Ala-Leu (SEQ ID NO:31), Gly-Gly-Phe- Gly (SEQ ID NO:32) or dipeptides such as Ala-Ala, Ala-Arg, Val-Cit, Val-Ala, Met- (D)Lys, Asn-(D)Lys, Val-(D)Asp, Phe-Lys, Ile-Val, Asp-Val, His-Val, NorVal-(D)Asp, Ala-(D)Asp, Met-Lys, Asn-Lys, Ile-Pro, Me3Lys-Pro, PhenylGly-(D)Lys, Met-(D)Lys, Asn-(D)Lys, Pro-(D)Lys, Met-(D)Lys, Asn-(D)Lys, Met-(D)Lys, Asn-(D)Lys. In certain embodiments, dipeptides are preferred over longer polypeptides due to hydrophobicity of the longer peptides. That is, linkers comprising an amino acid as set forth in SEQ ID NO:1-29 or 82-93 may further comprise any of the dipeptide or tetrapeptide motifs listed above. In certain embodiments, the dipeptide or tetrapeptide motifs listed above are directly coupled to a payload or are coupled to a payload via a self-immolative spacer. However, it is to be understood that the peptide linker itself, such as any of the linkers comprising an amino acid as set forth in SEQ ID NO:1-29 or 82-93, may be subject to enzymatic cleavage by endogenous peptidases or proteases. Enzymatically cleavable linkers may include a self-immolative spacer to spatially separate the payload from the site of enzymatic cleavage. The direct attachment of a payload to a peptide linker can result in proteolytic release of an amino acid adduct of the payload, thereby impairing its activity. The use of a self-immolative spacer allows for the elimination of the fully active, chemically unmodified payload upon amide or glycosidic bond hydrolysis. In certain embodiments, the peptide linker in accordance with the present invention is a self-immolative linker which comprises: a) a p-aminobenyzl alcohol moiety; or b) a 2,4-bis(hydroxymethyl)aniline moiety; or c) a p-aminobenzyl quaternary ammonium; or d) an ethylenediamine-based moiety; or e) an (aminomethyl)pyrrolidine-based moiety; or f) an aminomethyl-based moiety. One self-immolative spacer is the bifunctional para-aminobenzyl alcohol group, which is linked to the peptide through the amino group, forming an amide bond, while amine- containing drugs may be attached through carbamate functionalities to the benzylic hydroxyl group of the linker (PABC). The resulting prodrugs are activated upon protease-mediated cleavage, leading to a 1,6-elimination reaction releasing the unmodified drug, carbon dioxide, and remnants of the linker group. Heterocyclic variants of this self-immolative group have also been described. See for example, U.S. Pat. No.7,989,434, incorporated herein by reference. The para-aminobenzyl alcohol moiety may also be used to link a phenol- or hydroxyl-containing payload through the formation of a carbonate. The para-aminobenzyl moiety may also be used to link a tertiary- or heteroaryl-amine-containing payload through the formation of a quaternary ammonium (PABQ). That is, in certain embodiments, in the peptide linker according to the invention, the quaternary ammonium cation comprised in the p-aminobenzyl quaternary ammonium originates from an amine comprised in the payload. Preferably, the amine comprised in the payload is a tertiary amine or a heteroaryl-amine. Another self-immolative spacer is the 2,4-bis(hydroxymethyl)aniline group, which is linked to the peptide through the amino group, forming an amide bond, while amine- containing drugs may be attached through two carbamate functionalities via the two benzylic hydroxyl groups of the linker. The resulting prodrugs are activated upon protease-mediated cleavage, leading to payload release via successive 1,6- and 1,4- elimination processes. For hydroxyl-containing drugs, suitable self-immolative spacers include, but are not limited to, ethylenediamine-based carbamate (EDA), (aminomethyl)pyrrolidine-based carbamate (AMP) (see FIG. 33), or the aminomethyl moeity (AM). The release mechanism of this latter utilizes the lability of the hemiaminal functionality, which readily undergoes 1,2-elimination to release the desired alcohol. For thiol-containing drugs, suitable self-immolative spacers include, but are not limited to, the aminomethyl moeity (AM). The release mechanism of this latter utilizes the lability of the thiohemiaminal functionality, which readily undergoes 1,2-elimination to release the desired thiol. In some embodiments, the enzymatically cleavable linker is a ß-glucuronic acid-based linker. Facile release of the payload may be realized through cleavage of the ß- glucuronide glycosidic bond by the lysosomal enzyme ß-glucuronidase. This enzyme is present abundantly within lysosomes and is overexpressed in some tumor types, while the enzyme activity outside cells is low. ß-Glucuronic acid-based linkers may be used to circumvent the tendency of an antibody-payload conjugate to undergo aggregation due to the hydrophilic nature of ß-glucuronides. As mentioned above, in a particular embodiment, the chemical linker is or comprises a self-immolative linker. In exemplary embodiments, the payloads are attached to the peptide linker via a self- immolative linker to facilitate release of the unmodified drug. Even more preferably, the self-immolative linker is coupled to a peptide sequence that is efficiently cleaved by a protease or a peptidase. The cleavable peptide may be defined as part of the peptide linker or as part of the chemical linker that connects the peptide linker with the payload(s). The self-immolative linker may be any self-immolative linker known in the art. However, it is preferred that the self-immolative linker comprises a p-aminobenzyl alcohol moiety or a 2,4-bis(hydroxymethyl)aniline moiety. That is, in a particular embodiment, the self-immolative linker comprises a p- aminobenzyl alcohol moiety or a 2,4-bis(hydroxymethyl)aniline moiety. Self-immolative linkers comprising a p-aminobenyzl alcohol moiety may be used for coupling payloads to the C-terminus of a peptide. That is, the amino group of the p- aminobenzyl alcohol moiety may be coupled to the C-terminal carboxyl group of the peptide linker via an amide bond. Alternatively, or in addition, the amino group of the p-aminobenzyl alcohol moiety may be coupled to a carboxyl group in the side chain of an aspartate or glutamate residue in the peptide linker via an amide bond. The payload may be coupled to the hydroxyl group of the p-aminobenzyl alcohol moiety via a carbamate. In certain embodiments, the C-terminal amino acid of the peptide linker to which the p-aminobenzyl alcohol moiety may be coupled may be comprised in a motif that is efficiently cleaved by a peptidase, such as, without limitation, the sequence motif valine-citrulline. It is to be understood that the peptide linker in accordance with the present invention may comprise more than one p-aminobenzyl alcohol moiety. For example, a peptide linker according to the invention may comprise two peptide moieties, wherein the two peptide moieties are linked to each other via their N-terminal ends. In such embodiments, the peptide linker has two C-terminal ends and both C-terminal ends may be conjugated to a payload via a p-aminobenzyl alcohol moiety. A p-aminobenzyl alcohol moiety may also be used for coupling a payload to an amino acid side chain. For example, a payload may be coupled to the carboxyl group in the side chain of a glutamate or aspartate residue via a p-aminobenzyl alcohol moiety. The p-aminobenzyl alcohol moiety may be coupled to the carboxyl group in the side chain of a glutamate or aspartate residue either directly or via one or more amino acid residues. In certain embodiment, the p-aminobenzyl alcohol moiety may be coupled to the carboxyl group in the side chain of a glutamate or aspartate residue via the valine- citrulline or alanine-alanine sequences. In certain embodiments, an amine comprising payload may be coupled to a carboxyl group in the peptide linker by two or more aminobenzyl alcohol moieties. Self-immolative linkers comprising a 2,4-bis(hydroxymethyl)aniline moiety may be used for coupling two payloads to a single functional group comprised in a peptide linker. That is, a 2,4-bis(hydroxymethyl)aniline moiety may be coupled to a carboxyl group comprised in a peptide linker via its amino group. Payloads may then be coupled to each of the hydroxyl groups via a carbamate. By using linkers comprising 2,4-bis(hydroxymethyl)aniline moieties, peptide linkers comprising more than two payloads may be obtained. For example, a linker comprising four payloads may be obtained by coupling two payloads to the N-terminal end of a peptide linker via a 2,4-bis(hydroxymethyl)aniline moiety (indirectly via a second peptide moiety) and two more payloads to the C-terminal end of a peptide linker via another 2,4-bis(hydroxymethyl)aniline moiety. Similarly, peptide linkers comprising three payloads may be obtained by coupling two payloads to the peptide linker via a 2,4-bis(hydroxymethyl)aniline moiety and a third payload via a p-aminobenzyl alcohol moiety. In a particular embodiment, the invention relates to the peptide linker according to the invention, wherein the hydroxyl group comprised in the p-aminobenzyl alcohol moiety forms a carbamate with a payload. As mentioned above, a payload may be attached to the p-aminobenzyl alcohol moiety via a carbamate. That is, the payload preferably comprises a free amine group that is suitable to undergo formation of a carbamate. The skilled person is aware of methods to form a carbamate between a p-aminobenzyl alcohol moiety and an amine- comprising payload. In a particular embodiment, in the peptide linker according to the invention, the hydroxyl group comprised in the p-aminobenzyl alcohol moiety forms a carbonate with a payload. A payload may be attached to the p-aminobenzyl alcohol moiety via a carbonate. That is, the payload preferably comprises a free hydroxyl group that is suitable to undergo formation of a carbonate. The skilled person is aware of methods to form a carbonate between a p-aminobenzyl alcohol moiety and a hydroxyl-comprising payload. In a particular embodiment, in the peptide linker according to the invention, each of the hydroxyl groups comprised in the 2,4-bis(hydroxymethyl)aniline moiety forms a carbamate with a payload. That is, the 2,4-bis(hydroxymethyl)aniline moiety comprised in the peptide linker according to the invention may form two carbamates with two individual amine comprising payloads. In a particular embodiment, in the peptide linker according to the invention, the p- aminobenzyl moiety forms a quaternary ammonium with a payload. As mentioned above, a payload may be attached to the p-aminobenzyl via a quaternary ammonium. That is, the payload preferably comprises a tertiary- or a heteroaryl-amine that is suitable to undergo formation of a quaternary ammonium. The skilled person is aware of methods to form a quaternary ammonium between a p-aminobenzyl moiety and a tertiary- or a heteroaryl-amine-comprising payload. In a particular embodiment, in the peptide linker according to the invention, the self- immolative linker comprises an ethylenediamine carbamate (EDA) moiety. That is, payloads may be coupled to the peptide linker via an ethylenediamine carbamate (EDA) moiety. An EDA moiety may be coupled directly to the C-terminus of a peptide or to an aspartate or glutamate sidechain via an amide bond. EDA moieties preferably undergo carbamate formation with payloads comprising a hydroxyl group. An EDA moiety can also be used to connect an amplifier linked to two payloads. In a particular embodiment, in the peptide linker according to the invention, the self- immolative linker comprises an (aminomethyl)pyrrolidine-based carbamate (AMP) moiety. That is, payloads may be coupled to the peptide linker according to the invention via an (aminomethyl)pyrrolidine-based carbamate (AMP) moiety. An AMP moiety may be coupled directly to the C-terminus of a peptide or to an aspartate or glutamate sidechain via an amide bond. AMP moieties preferably undergo carbamate formation with payloads comprising a hydroxyl group. In a particular embodiment, in the peptide linker according to the invention, the self- immolative linker comprises an aminomethyl (AM) moiety. That is, payloads may be coupled to the peptide linker according to the invention via an aminomethyl (AM) moiety. An AM moiety may be coupled directly to the C-terminus of a peptide or to an aspartate or glutamate sidechain via an amide bond. AM moieties may be used to link payloads comprising a hydroxyl group, thereby forming a hemiaminal. However, AM moieties can also be used to link payloads comprising a thiol group, thereby forming a thiohemiaminal. In a particular embodiment, in the peptide linker according to the invention, at least one payload is attached to a side chain of a glutamate, aspartate, tryptophan, cysteine, lysine, tyrosine, serine, or threonine residue comprised in the peptide linker. As mentioned above, one or more payloads may be coupled to an amino acid side chain comprised in the peptide linker. The skilled person is aware of chemical linkers that are suitable for coupling a payload to an amino acid side chain, i.e., the carboxyl group in the side chain of a glutamate or aspartate residue, the thiol group in the side chain of a cysteine residue, the amino group in the side chain of a lysine residue or the hydroxy group in the side chain of a tyrosine, serine, or threonine residue. In a particular embodiment, the invention relates to the peptide linker according to the invention, wherein the peptide linker comprises two peptide moieties, and wherein the two peptide moieties are connected via their N-terminal amino acid residues with adicarboxylic acid linker (HO2C R CO2H).Certain linkers falling within the scope of the present invention comprise two peptide moieties, wherein the two peptide moieties are linked via their N-terminal amino acid residues. The N-terminal amino acids of the two peptide moieties may be linked via a dicarboxylic acid, wherein each carboxylic acid group comprised in the dicarboxylic acid forms an amide bond with an N-terminal amino group of a peptide moiety. Any dicarboxylic acid may be used to link two peptide moieties via their N-terminal amino acid residues. In certain embodiments, the dicarboxylic acid may be an aliphatic dicarboxylic acid. That is, the dicarboxylic acid may be ethanedioic acid, propanedioic acid, butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, nonanedioic acid or decanedioic acid. In certain embodiments, two peptide moieties are linked via their N-terminal amino acids with a butanedioic acid molecule. In certain embodiments, two peptide moieties are linked via their N-terminal amino acids with a pentanedioic acid molecule. Aliphatic dicarboxylic acids may comprise substituted or unsubstituted alkyl or alkenyl chains. In certain embodiments, the dicarboxylic acid may be an aromatic dicarboxylic acid. Aromatic dicarboxylic acids include, without limitation, phthalic acid, isophthalic acid, or terephthalic acid. It is to be understood that linking two peptide moieties via their N-terminal amino acids results in a peptide construct comprising no free N-terminal amino group that may be suitable for conjugation to a glutamine residue comprised in an antibody. Thus, peptide linkers comprising two N-terminally linked peptide moieties may comprise a lysine residue, a lysine mimetic or a lysine derivative to enable conjugation of the peptide linker to a glutamine moiety comprised in an antibody. In certain embodiments, the first peptide moiety comprised in the peptide linker may comprise any of the amino acid sequences set forth in SEQ ID NO:1-8, 11-14, 16-29 or 82-93. The second peptide moiety may have any amino acid sequence. In certain embodiments, the second peptide moiety may have a length of 2-100, preferably 2-50, more preferably 2-25, even more preferably 2-10, most preferably 2-5 amino acid residues. In certain embodiments, the second peptide moiety may be a dipeptide or a tripeptide. However, it is to be noted that the second peptide moiety may also be a single amino acid or a longer peptide. To enable efficient release of the payload, the second peptide moiety may comprise a peptide sequence that is efficiently cleaved by a peptidase. In certain embodiments, the second peptide moiety may have the sequence Asn, Ala, Ala-Ala, Ala-Asn, Val-Ala, Val-Cit, Ala-Arg, Arg-Ala, Ala-Ala-Arg (SEQ ID NO:34), Ala-Arg-Ala (SEQ ID NO:35), Ala-Ala-Asn (SEQ ID NO:36). That is, in certain embodiments, the peptide linker may comprise the structure: [payload 1]-[peptide 1]-[dicarboxylic acid]-[peptide 2]-[payload 2]; wherein [payload 1] and [payload 2] are payloads, [peptide 1] is a first peptide moiety, [peptide 2] is a second peptide moiety, and [dicarboxylic acid] is a dicarboxylic acid; wherein at least one of the peptide moieties 1 and / or 2 comprises a free amine, wherein the N-terminal end of peptide 1 and the N-terminal end of peptide 2 are connected via the dicarboxylic acid, wherein payload 1 is attached to the C-terminal end of peptide 1, preferably via a chemical linker, and wherein payload 2 is attached to the C-terminal end of peptide 2, preferably via a chemical linker. In such embodiments, the third payload may also be linked to the C-terminal end of peptide 1 and / or 2. Alternatively, the third payload may be linked to a side chain of an amino acid residue comprised in peptide 1 and / or 2. In certain embodiments, the peptide moiety comprising a free amine group is a peptide moiety comprising a lysine residue, a lysine mimetic or a lysine derivative, as defined elsewhere herein or a peptide linker comprising any one of the amino acid sequences set forth in SEQ ID NO:1-8, 11-14, 16-29 or 82-93. In certain embodiments, the peptide linker may comprise a first peptide moiety comprising a sequence set forth in SEQ ID NO:1-8, 11-14, 16-29 or 82-93 and a second moiety comprising the sequence Ala-Ala, wherein the first and second peptide moiety are linked via their N-terminal amino acids with a butanedioic acid molecule. In certain embodiments, the peptide linker may comprise a first peptide moiety comprising the sequence RKAA and a second moiety comprising the sequence Ala- Ala, wherein the first and second peptide moiety are linked via their N-terminal amino acids with a butanedioic acid molecule. Instead of coupling two peptide moieties via their N-terminal amino acid residues, a second peptide moiety may also be coupled to an amino acid side chain of a first peptide moiety. That is, the first peptide moiety comprised in the peptide linker may comprise any of the amino acid sequences set forth in SEQ ID NO:6, 11-12, 20-21, 23, 26-29 or 82-93. The second peptide moiety, that is the one positioned on the amino acid side chain, may have any amino acid sequence. In certain embodiments, the second peptide moiety may be a dipeptide or a tripeptide. However, it is to be noted that the second peptide moiety may also be a single amino acid or a longer peptide. To enable efficient release of the payload, the second peptide moiety preferably comprises a peptide sequence that is efficiently cleaved by a peptidase. In certain embodiments, the second peptide moiety may have the sequence Asn, Ala, Ala-Ala, Ala-Asn, Val-Ala, Val-Cit, Ala-Arg, Arg-Ala, Ala-Ala-Arg (SEQ ID NO:34), Ala-Arg-Ala (SEQ ID NO:35), Ala-Ala-Asn (SEQ ID NO:36). The peptide linker according to the invention comprises three or more payloads. The peptide linkers comprising the three or more payloads may be obtained by chemical synthesis. The skilled person is aware of methods for coupling a payload to an amino acid-based linker by chemical synthesis. For example, an amine-comprising payload (for e.g., auristatin analogs, exatecan), or a thiol-comprising payload (for e.g., maytansine analogs), or a hydroxyl-containing payload (for e.g., SN-38 analogs) may be attached to the C-terminus of an amino acid-based linker by chemical synthesis. However, the skilled person is aware of further reactions and reactive groups that may be utilized for coupling a payload to the N-terminus, C-terminus or the side chain of an amino acid or amino acid derivative by chemical synthesis. Typical reactions that may be used for coupling a payload to an amino acid-based linker by chemical synthesis include, without limitation: peptide coupling, activated ester coupling (NHS ester, PFP ester), click reaction (CuAAC, SPAAC), Michael addition (thiol maleimide conjugation). The coupling of payloads to peptides has been extensively described in the prior art, for example by Costoplus et al. (Peptide-Cleavable Self-immolative Maytansinoid Antibody-Drug Conjugates Designed To Provide Improved Bystander Killing. ACS Med Chem Lett.2019 Sep 27;10(10):1393-1399), Sonzini et al. (Improved Physical Stability of an Antibody-Drug Conjugate Using Host-Guest Chemistry. Bioconjug Chem.2020 Jan 15;31(1):123-129), Bodero et al. (Synthesis and biological evaluation of RGD andisoDGR peptidomimetic- -amanitin conjugates for tumor-targeting. Beilstein J. Org.Chem. 2018, 14, 407–415), Nunes et al. (Use of a next generation maleimide in combination with THIOMAB™ antibody technology delivers a highly stable, potent and near homogeneous THIOMAB™ antibody-drug conjugate (TDC). RSC Adv., 2017,7, 24828-24832), Doronina et al. (Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006 Jan-Feb;17(1):114-24), Nakada et al. (Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorg Med Chem Lett. 2016 Mar 15;26(6):1542-1545) and Dickgiesser et al. (Site-Specific Conjugation of Native Antibodies Using Engineered Microbial Transglutaminases. Bioconjug Chem.2020 Mar 12. doi: 10.1021 / acs.bioconjchem.0c00061). It is to be understood that the payload may be coupled to the N-terminal and / or to the C-terminal end of a peptide-based or a peptide-comprising linker according to the invention. In certain embodiments, a payload may be coupled directly to the N-terminal amino group or the C-terminal carboxyl group of a peptide or an amino acid residue. The skilled person is aware of reactive groups that are suitable for coupling a payload to an amino acid residue. For example, an amine-comprising payload may be coupled to the C-terminal carboxyl group of an amino acid residue via an amide bond. Alternatively, a payload comprising a thiol group or and hydroxyl group may be coupled to the C-terminal carboxyl group of an amino acid via a thioester or an ester bond, respectively. A payload comprising a carboxylic acid group may be coupled to the N- terminal amino group of an amino acid residue via an amide bond. In certain embodiments, a payload may be coupled indirectly to the N- and / or C- terminal end of a peptide or amino acid residue comprised in the linker according to the invention. The skilled person is aware of linker molecules that may be used to couple a payload to the N-terminal amino group or the C-terminal carboxyl group of an amino acid residue comprised in the linker according to the invention. In certain embodiments, a payload comprising a hydroxyl group may be coupled to the N-terminus of an amino acid residue via a linker molecule. For example, payloads comprising a hydroxyl group may be coupled to an N-terminal amino group via a carbamate linker. In certain embodiments, a payload comprising a thiol group may be coupled to the N- terminus of an amino acid residue via a linker molecule. For example, payloads comprising a thiol group may be coupled to an N-terminal amino group via a thiocarbamate linker. Alternatively, payloads comprising a thiol group may be coupled to an N-terminal amino group via an alkyl linker molecule comprising a carboxyl group and a thiol group. In certain embodiments the alkyl linker molecule may be a 3- mercaptopropionic acid linker molecule, wherein the payload forms a di-sulfur bond with the thiol group comprised in the 3-mercaptopropionic acid linker molecule. In certain embodiments, a payload comprising an amide group may be coupled to the N-terminus of an amino acid residue via a linker molecule. For example, payloads comprising an amine group may be coupled to an N-terminal amino group via a dicarboxylic acid linker molecule, wherein the each of the carboxylic acid groups comprised in the dicarboxylic acid linker forms an amide bond with the payload and the amino group of the N-terminal amino acid residue. Examples of dicarboxylic acids that may be used as linker molecules in the present invention are, without limitation, succinic acid or pimelic acid. Alternative linker molecules for indirectly coupling payloads to the N-terminus of an amino acid residue comprised in the peptide linker according to the invention or linker molecules that are suitable for indirectly coupling payloads to the C-terminus of an amino acid residue comprised in the peptide linker according to the invention have been described in the art and are encompassed by the present invention. In another particular embodiment, one or more payload is attached to the N-terminal end of an amine-comprising peptide linker and wherein one or more payload is attached to the C-terminal end of said amine-comprising peptide linker. In certain embodiments, one payload may be attached to the N-terminal end of an amine-comprising peptide linker and two payloads may be attached to the C-terminal end of said amine-comprising peptide linker or vice versa. That is, the peptide linker may be a DAR6 linker. In certain embodiments, two payloads may be attached to the N-terminal end of an amine-comprising peptide linker and two payloads may be attached to the C-terminal end of said amine-comprising peptide linker or vice versa. That is, the peptide linker may be a DAR8 linker. The amine-comprising peptide linker maybe any one of the lysine-comprising peptide linkers disclosed herein, including peptide linkers comprising a lysine mimetic or a lysine derivative as defined herein. In certain embodiments, the linker may comprise the following structure (in N -> C direction): [payload1]-[(Aa)m-(Lys)-(Aa)n]-[payload 2]; wherein [payload 1] and [payload 2] are payloads, Aa may be any amino acid residue; m and n may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; and Lys is a lysine residue, a lysine mimetic or a lysine derivative, wherein [payload 1] is directly or indirectly attached to an N-terminal end of an (Aa) or (Lys) residue, and wherein [payload 2] is directly or indirectly attached to a C-terminal end of an (Aa) or (Lys) residue. In such embodiments, the third payload may also be attached to the same N-terminal end of the (Aa) or (Lys) residue and / or the same C-terminal end of the (Aa) or (Lys) residue. Alternatively, the third payload may be linked to a side chain of an (Aa) residue. In certain embodiments, the linker may comprise the following structure: [payload1]-[(Aa)m-(Arg / His)-(Aa)n-(Lys)-(Aa)o]-[payload 2]; wherein [payload 1] and [payload 2] are payloads, Aa may be any amino acid residue; m, n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; and Arg may be an arginine residue, an arginine mimetic or an arginine derivative; His may be a histidine residue, a histidine mimetic or a histidine derivative Lys is a lysine residue, a lysine mimetic or a lysine derivative, wherein [payload 1] is directly or indirectly attached to an N-terminal end of an (Aa) or (Arg / His) residue, and wherein [payload 2] is directly or indirectly attached to a C-terminal end of an (Aa) or (Lys) residue. In such embodiments, the third payload may also be attached to the same N-terminal end of the (Aa) or (Arg / His) residue and / or the same C-terminal end of the (Aa) or (Lys) residue. Alternatively, the third payload may be linked to a side chain of an (Aa) residue. In certain embodiments, the linker may comprise the following structure: [payload1]-[(Aa)m-(Lys)-(Aa)n-(Arg / His)-(Aa)o]-[payload 2]; wherein [payload 1] and [payload 2] are payloads, Aa may be any amino acid residue; m, n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or0 to 4; and Arg may be an arginine residue, an arginine mimetic or an arginine derivative; His may be a histidine residue, a histidine mimetic or a histidine derivative Lys is a lysine residue, a lysine mimetic or a lysine derivative, wherein [payload 1] is directly or indirectly attached to an N-terminal end of an (Aa) or (Lys) residue, and wherein [payload 2] is directly or indirectly attached to a C-terminal end of an (Aa) or (Arg / His) residue. In such embodiments, the third payload may also be attached to the same N-terminal end of the (Aa) or (Lys) residue and / or the same C-terminal end of the (Aa) or (Arg / His) residue. Alternatively, the third payload may be linked to a side chain of an (Aa) residue. In certain embodiments, the first payload and / or second payload and / or third payload are linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker; preferably wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker, or vice versa. In certain embodiments, the linker comprises the following structure (in N -> C direction): [payload1]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o—Z-X-[payload 2]; or [payload2]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o—Z-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer is (CH2)2; and X is either absent or a self-immolative group, preferably PABC. In such embodiments, the third payload may be attached to any suitable position of the linker. In certain embodiments, the third payload may be attached to a side chain of an residue (Aa) comprised in the linker. More preferably, the present invention relates to an ADC as defined herein, wherein the linker comprises the following structure: [payload1]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 2]; or [payload2]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2; and X is either absent or a self-immolative group, preferably PABC. In such embodiments, the third payload may be attached to any suitable position of the linker. In certain embodiments, the third payload may be attached to a side chain of an residue (Aa) comprised in the linker. In a further embodiment, the residues (Aa)m+ (Aa)n+ (Aa)oare > 0. In another embodiment, the residues (Aa)n+ (Aa)oare > 0. Accordingly, the Lys residue may form a peptide bind with at least one additional amino acid residue. In a further embodiment, the spacer Z2is a dicarboxylic acid, as disclosed elsewhere herein. This dicarboxylic acid links the N-terminal end of the peptide comprising the (Lys) residue to the N-terminal end of the amino acid or peptide moiety (Aa)m. By linking these two moieties via their N-terminal ends, a peptide linker comprising two C-terminal ends is formed. These two C-terminal ends can be directly or indirectly linked to payloads, as disclosed elsewhere herein. In such embodiments, it is to be understood that (Aa)mhas to be >0. Accordingly, in a particular embodiment, the invention relates to the ADC according to the invention, wherein Z2is a dicarboxylic acid linking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and wherein one payload is directly or indirectly linked to the C-terminal end of (Aa)mand the other payload is directly or indirectly linked to the C-terminal end of (Lys) or (Aa)o, or vice versa. In another embodiment, the present invention relates to an ADC as defined herein, wherein the linker comprises the following structure: [payload1]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 2]; or [payload2]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m is an integer ranging from 1 to 10, e.g., 1 to 6 or 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mto the N- terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC. In such embodiments, the third payload may be attached to any suitable position of the linker. In certain embodiments, the third payload may be attached to a side chain of an residue (Aa) comprised in the linker. As discussed herein above, the linker may comprise at least one positively charged amino acid residue in addition to the lysine residue. In a particular embodiment, the invention relates to the ADC according to the invention, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction). Inanother embodiment, (Aa)n-(Lys)-(Aa)o is or comprises RK or RKAA (in N -> Cdirection).In such embodiments, the moiety (Aa)m is a single amino acid residue or a peptide having a length of 2 – 10, 2 – 6, or 2 – 4 amino acid residues. In certain embodiments, the moiety (Aa)m has or comprises the sequence Ala-Ala (AA) or Ala-Arg-Ala (ARA). Linkers comprising three payloads, i.e., a the first, second and third payload, may have the following structure: ([payload]-X-Z1-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-Z2-(Aa)n(Lys)-(Aa)o-Z3-X-[payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X-[payload])2; wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises at least one of each the first, second and third payload; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, e.g., 0 to 6, 0 to 4, or wherein n + o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, e.g., wherein the spacer comprises (CH2)2, or wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, preferably PABC. In certain embodiments, linkers comprising three payloads may have the following structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X- [payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-X- [payload])2; wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises at least one of each the first, second and third payload; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, e.g., 1 to 6 or 1 to 4; n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC. Linkers comprising four payloads may have the following structure: ( - (Aa)p / p*-Z3-X-[payload])2; wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises at least one of each the first, second and third payload; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, e.g., 0 to 6, 0 to 4, or wherein n + o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, e.g., wherein the spacer comprises (CH2)2, and / or wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, preferably PABC. In certain embodiments, linkers comprising four payloads may have the following structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N- ((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2; wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises at least one of each the first, second and third payload; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid as defined herein linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC. The linkers may comprise at least one additional positively charged amino acid residue in addition to the lysine residue, as explained in detail elsewhere herein. In certain embodiments, the third payload is linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker; e.g., wherein the third payload is linked to the C-terminus of the peptide linker. In certain embodiments, the first payload and / or second payload and / or the third payload are linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker; e.g., wherein the first payload and the second payload and the third payload are linked to the N-terminus of the peptide linker; or wherein the first payload and the second payload and the third payload are linked to the C-terminus of the peptide linker; or wherein the first payload and the second payload are linked to the N-terminus of the peptide linker and wherein the third payload is linked to the C-terminus of the peptide linker; or wherein the first payload and the third payload are linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker; or wherein the second payload and the third payload are linked to the N-terminus of the peptide linker and wherein the first payload is linked to the C-terminus of the peptide linker; or wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload and the third payload are linked to the C-terminus of the peptide linker; or wherein the second payload is linked to the N-terminus of the peptide linker and wherein the first payload and the third payload are linked to the C-terminus of the peptide linker; or wherein the third payload is linked to the N-terminus of the peptide linker and wherein the first payload and the second payload are linked to the C-terminus of the peptide linker. In certain embodiments, the linker consists or comprises the following structure: [payload1]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o-Z-X-[payload 2] / [payload 3]; or [payload1] / [payload 3]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o-Z-X-[payload 2]; or [payload2]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o-Z-X-[payload 1] / [payload 3]; or [payload2] / [payload 3]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o-Z-X-[payload 1]; or [payload1] / [payload 2]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o-Z-X-[payload 3]; or [payload3]-X-Z-(Aa)m-Z-(Aa)n(Lys)-(Aa)o-Z-X-[payload 1] / [payload 2] wherein [payload 1] is said first payload; [payload 2] is said second payload; [payload 3] is said third payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z is either absent or a spacer comprising an alkyl or a heteroalkyl group, e.g., wherein the spacer is (CH2)2; and X is either absent or a self-immolative group, e.g., PABC. In a particular embodiment, the invention relates to the ADC according to the invention, wherein two payloads are linked to the same functional group of the peptide linker, e.g., via a chemical linker comprising a disubstituted amine. That is, In certain embodiments, the linker consists of or comprises the structure: ([payload]-X-Z1-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-Z2-(Aa)n(Lys)-(Aa)o-Z3-X-[payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X- ( - (Aa)p / p*-Z3-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4, or wherein n + o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, e.g., wherein the spacer comprises (CH2)2, even more preferably wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, e.g., PABC. In certain embodiment, the invention relates to the ADC according to the invention, wherein the linker consists of or comprises the structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X- [payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-X- [payload])2; or ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N- ((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, e.g., 1 to 6 or 1 to 4; n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid as defined herein linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, e.g., PABC. The linkers may comprise at least one additional positively charged amino acid residue in addition to the lysine residue, as explained in detail elsewhere herein. That is, in a particular embodiment, the invention relates to the ADC according to the invention, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction). In another particular embodiment, the invention relates to the ADCaccording to the invention, wherein (Aa)n-(Lys)-(Aa)o is or comprises RK or RKAA (inN -> C direction). In a preferred embodiment, the present invention relates to an ADC as defined herein, wherein said ADC comprises more than one first payloads and / or more than one second payloads and / or more than one third payloads. As already outlined above, the peptide linker in accordance with the present invention comprises or contains at least three payloads, i.e., the “first payload”, the “second payload” and the “third payload”. If the peptide linker comprises or contains three payloads, these three payloads are different in structure, i.e., the first payload is a camptothecin cytotoxic molecule which is cell-permeable; and the second payload is a camptothecin cytotoxic molecule which is not cell-permeable; and the third payload is not a camptothecin derivative cytotoxic molecule and is preferably a toxin, preferably, anti-mitotic drug, tubulin polymerization- blocking agent, and / or auristatin, more preferably, an MMAE as defined herein. If the peptide linker comprises or contains more than three payloads, the payloads may be identical or may be different in structure while at least two of these payloads may be identical in structure. Coupling two or more identical payloads to a peptide linker allows increasing the concentration of the payload in the target tissue or cell of an antibody-payload conjugate. For example, if the peptide linker of an antibody-payload conjugate comprises two or more identical toxins (resulting in a DAR > 4 ADC), the concentration of the toxin in the target tissue or cell will be higher compared to a conventional DAR2 ADC. With the peptide linkers of the present invention, ADCs comprising 6, 8 or more identical payload molecules may be obtained. In a particular embodiment, the peptide linker in accordance with the present invention comprises between 3 and 6 payloads. In a particular embodiment, the peptide linker in accordance with the present invention comprises or contains 3 payloads, i.e., a as a first payload a single topoisomerase I inhibitor which is cell-permeable; and as a second payload a single topoisomerase I inhibitor which is not cell-permeable; and as a third payload a single toxin, e.g., an anti- mitotic drug, tubulin polymerization-blocking agent, and / or auristatin, e.g., an MMAE as defined herein. Further embodiments are preferred that correspond to the above-described embodiments wherein the peptide linker in accordance with the present invention comprises between 3 or 4 payloads. The above-defined three payloads can be coupled in different ways to a peptide linker. As mentioned above, the inventors identified different ways to couple two or more payloads to a peptide linker. In certain embodiments, the first payload and / or second payload and / or the third payload are linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker. In certain embodiments, two or three payloads may be coupled to the C-terminal end of a peptide linker. In other embodiments two or three payloads may be coupled to the N-terminal end of a peptide linker. In yet another embodiment, one or two or three payloads may be coupled each to the N-terminal end of a peptide linker and to the C- terminal end of a peptide linker. In certain embodiments, three payloads may be coupled to the C-terminal end of a peptide linker. In other embodiments, three payloads may be coupled to the N-terminal end of a peptide linker. In yet another embodiment, one or two or three payloads may be coupled each to the N-terminal end of a peptide linker and to the C-terminal end of a peptide linker. In another particular embodiment, one or more payload is attached to the N-terminal end of an amine-comprising peptide linker and one or more payload is attached to the C-terminal end of said amine-comprising peptide linker. In another particular embodiment, two payloads are attached to the N-terminal end of a peptide linker and one payload is attached to the C-terminal end of said peptidelinker. An example for a corresponding arrangement is illustrated in Figure 8.In certain embodiments, one or two or three payloads may be attached each to the N- terminal end of an amine-comprising peptide linker and one or two or three payloads may be attached each to the C-terminal end of said amine-comprising peptide linker. In one embodiment, the present invention relates to an ADC as defined herein, wherein the third payload is an MMAE. In another embodiment, the present invention relates to an ADC as defined herein, wherein the linker comprises or consists of the following structure:

[0002] In an embodiment, the present invention relates to an ADC as defined herein, wherein said ADC consists of two first payloads and two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”). Accordingly, in this embodiment, the peptide linker in accordance with the present invention comprises or contains 3 payloads, i.e., as a first payload: one topoisomerase I inhibitor which is cell-permeable; and as a second payload: one topoisomerase I inhibitor which is not cell-permeable; and one third payload: e.g., as a third payload one toxin, such as an anti-mitotic drug, or tubulin polymerization-blocking agent, and / or auristatin, e.g., MMAE as defined herein. It is to be understood that the payloads may be directly or indirectly attached to the N- terminal end and to the C-terminal end of the peptide linker. In one embodiment, a one payload may be directly attached to the N-terminal amino group of the peptide linker and another payload may be directly attached to the C-terminal carboxyl group of the peptide linker. It is also contemplated that the payloads are indirectly attached to the N-terminal end and to the C-terminal end of the peptide linker, for example with any one of the chemical linkers described herein. In particular, a payload may be indirectly attached to the N-terminal end of the peptide linker via a dicarboxylic acid and a second peptide moiety, as described in more detail elsewhere herein. Furthermore, all payloads may be attached to the peptide linker or the chemical linker via a self-immolative moiety, such as any one of the self-immolative moiety disclosed herein. While the linker comprised in the ADC according to the invention is a peptide linker, as described in detail herein, the linker may as well be any chemical linker, as long as the linker comprises, at least, a cell-permeable topoisomerase I inhibitor, a non-cell- permeable topoisomerase I inhibitor and a third payload. Moreover, the chemical linker may comprise any of the cleavable moieties, in particular any of the self-immolative moieties, described herein. As already explained above, the present invention relates to an ADC, i.e., an antibody- linker conjugate comprising any of the linkers defined herein. That is, the linker comprising at least a cell-permeable topoisomerase I inhibitor, a non- cell-permeable topoisomerase I inhibitor may be conjugated to an antibody by any suitable conjugation method, at any suitable conjugation site. As described herein above, the ADC of the invention has the formula A-L, wherein A is an antibody or an antibody fragment, and L is a linker. The skilled person is aware that antibodies typically comprise two identical light chains and two identical heavy chains. Consequently, any potential conjugation site in an antibody is typically present in both chains. Thus, the skilled person would understand that ADCs having the formula A-L also encompass ADCs having the formula L-A-L (or A-(L)2), where one linker is conjugated to a corresponding position in each antibody chain. Thus, in an alternative embodiment, the invention relates to an antibody-drug conjugate (ADC) having the formula L-A-L, wherein A is an antibody or an antibody fragment and wherein each L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e.g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin, e.g., an MMAE (Monomethyl auristatin E). In such embodiments, the antibody may be a native or engineered full-length antibody comprising two heavy chains and two light chains, e.g., a full length IgG antibody, as described elsewhere herein. However, also encompassed herein are ADCs comprising only a single conjugation site. Such ADCs may comprise, without limitation, single chain antibody fragments or engineered antibodies having only a single conjugation site. In such embodiments, the ADC may be conjugated with only a single linker and thus have the formula A-L. To encompass embodiments where the antibody is conjugated to one or more linker, the ADC may be defined to comprise the formula A-L. Accordingly, in a particular embodiment, the invention relates to an antibody-drug conjugate (ADC) comprising the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e.g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin, e.g., an MMAE (Monomethyl auristatin E). In certain embodiments the amine comprising peptide linkers according to the invention are conjugated to a glutamine residue in an antibody. Such conjugation can be achieved with a transglutaminase, as described in more detail elsewhere herein. As such, in a particular embodiment, the invention relates to the ADC / antibody-payload conjugate according to the invention, wherein the peptide linker is conjugated to theantibody via an isopeptide bond formed between a -carboxamide group of a glutamineresidue comprised in the antibody and the primary amine comprised in an amino acid residue of the peptide linker. Accordingly, the skilled person would readily understand that the primary amine comprised in the peptide linker disclosed herein is no longer present once the peptide linker has been conjugated to the antibody. The term “antibody” has already been defined above. In a particular embodiment, the invention relates to an ADC / antibody-payload conjugate according to the invention, wherein the peptide linker is conjugated to a glutamine residue comprised in an Fc domain of the antibody. That is, the peptide linker according to the invention is preferably conjugated to a glutamine residue comprised in an Fc domain of an antibody. The linkers of the invention may be conjugated to any Gln residue in the Fc domain of an antibody that can serve as a substrate for a transglutaminase. Typically, the term Fc domain as used herein refers to the last two constant region immunoglobulin domains of IgA, IgD and IgG (CH2 and CH3) and the last three constant region domains of IgE, IgY and IgM (CH2, CH3 and CH4). That is, the linker according to the invention may be conjugated to the CH2, CH3 and, where applicable, CH4 domains of the antibody. For example, the peptide linker according to the invention may be conjugated to an endogenous glutamine residue (e.g., Q295 of an IgG1 antibody) or to a glutamine residue that has been introduced into the Fc domain of the antibody be genetic engineering. That is, in a particular antibody, the invention relates to an ADC / antibody-payload conjugate according to the invention, wherein the glutamine residue to which the peptide linker is conjugated is glutamine residue Q295 (EU numbering) of the CH2 domain of an IgG antibody. It is important to understand that Q295 is an extremely conserved amino acid residue in IgG type antibodies. It is conserved in human IgG1, 2, 3, 4, as well as in rabbit and rat antibodies amongst others. Hence, being able to use Q295 is a considerable advantage for making therapeutic antibody-payload conjugates. Even though residue Q295 is extremely conserved among IgG type antibodies, some IgG type antibodies do not possess this residue, such as mouse and rat IgG2a antibodies. Thus, it is to be understood that the antibody used in the method of the present invention is preferably an IgG type antibody comprising residue Q295 (EU numbering) of the CH2 domain. In the literature discussing the conjugation of linkers to a CH2 Gln residue by means of a transglutaminase, the focus has been on small, low-molecular weight substrates. However, to accomplish such conjugation, deglycosylation of the asparagine residue at position N297, or the use of an aglycosylated antibody, has been described as necessary (WO 2015 / 015448; WO 2017 / 025179; WO 2013 / 092998). Quite surprisingly, and against all expectations, however, site-specific conjugation to Q295 of glycosylated antibodies is indeed efficiently possible by using the above discussed peptide linker structure. In particular, coupling of peptide linkers comprising two or more payloads was achieved with, for most of them, a conjugation efficiency greater than 90%. Even though Q295 is very close to N297, which is, in its native state, glycosylated, using the specified peptide linkers disclosed herein still allows for efficient conjugation to Q295. The substitution of N297 against another amino acid may have unwanted effects, as it may affect the overall stability of the entire Fc domain (Subedi et al, The Structural Role of Antibody N-Glycosylation in Receptor Interactions. Structure 2015, 23 (9), 1573-1583), and the efficacy of the entire conjugate as a consequence that can lead to increased antibody aggregation and a decreased solubility (Zheng et al.; The impact of glycosylation on monoclonal antibody conformation and stability. Mabs-Austin 2011, 3 (6), 568-576). Further, the glycan that is present at N297 has important immunomodulatory effects, as it triggers antibody dependent cellular cytotoxicity (ADCC) and the like. These immunomodulatory effects would get lost upon deglycosylation or any of the other approaches discussed above to obtain an aglycosylated antibody. Further, any sequence modification of an established antibody can also lead to regulatory problems, which is problematic because very often an accepted and clinically validated antibody is used as a starting point for ADC conjugation. Hence, in view of the above, in the present invention, for the conjugation of an IgG antibody at residue Q295 (EU numbering) of the CH2 domain of the antibody, preferably, an antibody is used that is glycosylated at residue N297 (EU numbering) of the CH2 domain. However, it is expressly stated that the present invention also encompasses the conjugation of deglycosylated or aglycosylated antibodies at residue Q295 or any other suitable Gln residue of the antibody, wherein the Gln residue may be an endogenous Gln residue or a Gln residue that has been introduced by molecular engineering. Thus, in a particular embodiment, the invention relates to the antibody-payload conjugate according to the invention, wherein the glutamine residue to which the peptide linker is conjugated has been introduced into the heavy or light chain of the antibody by molecular engineering. The term “molecular engineering,” as used herein, refers to the use of molecular biology methods to manipulate nucleic acid sequences. In the context of the present invention, molecular engineering may be used to introduce Gln residues into the heavy or light chain of an antibody. In general, two different strategies to introduce Gln residues into the heavy or light chain of an antibody are envisioned within the present invention. First, single residues of the heavy or light chain of an antibody may be substituted with a Gln residue. Second, Gln-containing peptide tags consisting of two or more amino acid residues may be integrated into the heavy or light chain of an antibody. For that, the peptide tag may either be integrated into an internal position of the heavy or light chain, that is, between two existing amino acid residues of the heavy or light chain or by replacing them, or the peptide tag may be fused (appended) to the N- or C-terminal end of the heavy or light chain of the antibody. For example, an amino residue of the heavy or light chain of an antibody may be substituted with a Gln residue, provided that the resulting antibody can be conjugated with the linkers of the invention by a microbial transglutaminase. In certain embodiments, the antibody is an antibody wherein amino acid residue N297 (EU numbering) of the CH2 domain of an IgG antibody is substituted, in particular wherein the substitution is an N297Q substitution. Antibodies comprising an N297Q mutation may be conjugated to more than one linker per heavy chain of the antibody. For example, antibodies comprising an N297Q mutation may be conjugated to four linkers, wherein one linker is conjugated to residue Q295 of the first heavy chain of the antibody, one linker is conjugated to residue N297Q of the first heavy chain of the antibody, one linker is conjugated to residue Q295 of the second heavy chain of the antibody and one linker is conjugated to residue N297Q of the second heavy chain of the antibody. The skilled person is aware that replacement of residue N297 of an IgG antibody with a Gln residue results in an aglycosylated antibody. That is, in a particular embodiment, the invention relates to the antibody-payload conjugate according to the invention, wherein the glutamine residue that has been introduced into the heavy or light chain of the antibody by molecular engineering is N297Q (EU numbering) of the CH2 domain of an aglycosylated IgG antibody. In a particular embodiment, the invention relates to an ADC / antibody-payload conjugate according to the invention, wherein the glutamine residue that has been introduced into the heavy or light chain of the antibody by molecular engineering is comprised in a peptide that has been (a) integrated into the heavy or light chain of the antibody or (b) fused to the N- or C-terminal end of the heavy or light chain of the antibody. Instead of substituting single amino acid residues of an antibody, peptide tags comprising a Gln residue that is accessible for a transglutaminase may be introduced into the heavy or light chain of the antibody. Such peptide tags may be fused to the N- or C-terminus of the heavy or light chain of the antibody. Alternatively, peptide tags may be inserted into the heavy or light chain of an antibody at a suitable position. Preferably, peptide tags comprising a transglutaminase-accessible Gln residue are fused to the C-terminus of the heavy chain of the antibody. Even more preferably, the peptide tags comprising a transglutaminase-accessible Gln residue are fused to the C- terminus of the heavy chain of an IgG antibody. Several peptide tags that may be fused to the C-terminus of the heavy chain of an antibody and serve as substrate for a microbial transglutaminase are described in WO 2012 / 059882 and WO 2016 / 144608. Thus, in a particular embodiment, the invention relates to the antibody-payload conjugate according to the invention, wherein the peptide comprising the Gln residue has been fused to the C-terminal end of the heavy chain of the antibody. Exemplary peptide tags that may be introduced into the heavy or light chain of an antibody, in particular fused to the C-terminus of the heavy chain of the antibody, are LLQGG (SEQ ID NO:70), LLQG (SEQ ID NO:37), LSLSQG (SEQ ID NO:38), GGGLLQGG (SEQ ID NO:39), GLLQG (SEQ ID NO:40), LLQ(SEQ ID NO:41), GSPLAQSHGG (SEQ ID NO:42), GLLQGGG (SEQ ID NO:43), GLLQGG (SEQ ID NO:44), GLLQ (SEQ ID NO:45), LLQLLQGA (SEQ ID NO:46), LLQGA(SEQ ID NO:47), LLQYQGA (SEQ ID NO:48), LLQGSG (SEQ ID NO:49), LLQYQG (SEQ ID NO:50), LLQLLQG (SEQ ID NO:51), SLLQG (SEQ ID NO:52), LLQLQ (SEQ IDNO:53), LLQLLQ (SEQ ID NO:54), LLQGR (SEQ ID NO:55), EEQYASTY (SEQ IDNO:56), EEQYQSTY (SEQ ID NO:57), EEQYNSTY (SEQ ID NO:58), EEQYQS (SEQID NO:59), EEQYQST (SEQ ID NO:60), EQYQSTY (SEQ ID NO:61), QYQS (SEQ IDNO:62), QYQSTY (SEQ ID NO:63), YRYRQ (SEQ ID NO:64), DYALQ (SEQ IDNO:65), FGLQRPY (SEQ ID NO:66), EQKLISEEDL (SEQ ID NO:67), LQR (SEQ IDNO:68) and YQR (SEQ ID NO:69).The skilled person is aware of methods to substitute amino acid residues of antibodies or to introduce peptide tags into antibodies, for example by methods of molecular cloning as described in Sambrook, Joseph. (2001). Molecular cloning: a laboratory manual. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press. While it is preferred herein that antibodies are conjugated at a glutamine reside by means of a transglutaminase, as described herein above, the antibody may also be conjugated at a lysine residue. The lysine residue may be an endogenous lysine residue or a lysine residue that has been introduced into the antibody by genetic engineering. In such embodiments, the peptide linker may comprise a glutamine residue that can form an isopeptide bond with the lysine residue of the antibody. Conjugation may be catalyzed by a transglutaminase, as described herein. In general, the skilled person is aware of methods to determine at which position of an antibody a peptide linker is conjugated. For example, the conjugation site may be determined by proteolytic digestion of the antibody-payload conjugate and LC-MS analysis of the resulting fragments. For example, samples may be deglycosylated with GlyciNATOR (Genovis) according to the instruction manual and subsequently digestedwith trypsin gold (mass spectrometry grade, Promega), respectively. Therefore, 1 gof protein may be incubated with 50 ng trypsin at 37 °C overnight. LC-MS analysis may be performed using a nanoAcquity HPLC system coupled to a Synapt-G2 mass spectrometer (Waters). For that, 100 ng peptide solution may be loaded onto an Acquity UPLC Symmetry C18 trap column (Waters, part no.186006527) and trappedwith 5 L / min flow rate at 1 % buffer A (Water, 0.1 % formic acid) and 99 % buffer B (acetonitrile, 0.1 % formic acid) for 3 min. Peptides may then be eluted with a linear gradient from 3 % to 65 % Buffer B within 25 min. Data may be acquired in resolution mode with positive polarity and in a mass range from 50 to 2000 m / z. Other instrument settings may be as follows: capillary voltage 3,2 kV, sampling cone 40 V, extraction cone 4.0 V, source temperature 130 °C, cone gas 35 L / h, nano flow gas 0.1 bar, and purge gas 150 L / h. The mass spectrometer may be calibrated with [Glu1]- Fibrinopeptide. Further, the skilled person is aware of methods to determine the drug-to-antibody (DAR) ratio or payload-to-antibody ratio of an antibody-payload construct. For example, the DAR may be determined by hydrophobic interaction chromatography (HIC) or LC-MS. For hydrophobic interaction chromatography (HIC), samples may be adjusted to 0.5 Mammonium sulfate and assessed via a MAB PAK HIC Butyl column (5 m, 4.6 x 100mm, Thermo Scientific) using a full gradient from A (1.5 M ammonium sulfate, 25 mM Tris HCl, pH 7.5) to B (20 % isopropanol, 25 mM Tris HCl, pH 7.5) over 20 min at 1mL / min and 30 °C. Typically, 40 g sample may be used and signals may be recordedat 280 nm. Relative HIC retention times (HIC-RRT) may be calculated by dividing the absolute retention time of the ADC DAR 2 species by the retention time of the respective unconjugated mAb. For LC-MS DAR determination, ADCs may be diluted with NH4HCO3to a finalconcentration of 0.025 mg / mL. Subsequently, 40 L of this solution may be reducedwith 1 L TCEP (500 mM) for 5 min at room temperature and then alkylated by adding10 L chloroacetamide (200 mM), followed by overnight incubation at 37 °C in the dark.For reversed phase chromatography, a Dionex U3000 system in combination with the software Chromeleon may be used. The system may be equipped with a RP-1000column (1000 Å, 5 m, 1.0 × 100 mm, Sepax) heated to 70 °C, and an UV-detector setto a wavelength of 214 nm. Solvent A may consist of water with 0.1 % formic acid and solvent B may comprise 85 % acetonitrile with 0.1 % formic acid. The reduced and alkylated sample may be loaded onto the column and separated by a gradient from 30 – 55 % solvent B over the course of 14 min. The liquid chromatography system may be coupled to a Synapt-G2 mass spectrometer for identification of the DAR species. The capillary voltage of the mass spectrometer may be set to 3 kV, the sampling cone to 30 V and the extraction cone may add up to a value of 5 V. The source temperature may be set to 150 °C, the desolvation temperature to 500 °C, the cone gas to 20 l / h, the desolvation gas to 600 l / h, and the acquisition may be made in positive mode in a mass range from 600-5000 Da with 1 s scan time. The instrument may be calibrated with sodium iodide. Deconvolution of the spectra may be performed with the MaxEnt1 algorithm of MassLynx until convergence. After assignment of the DAR species to the chromatographic peaks, the DAR may be calculated based on the integrated peak areas of the reversed phase chromatogram. In a particular embodiment, the invention relates to the ADC / antibody-payload conjugate of the present invention, wherein the IgG antibody is a glycosylated IgG antibody. In certain embodiments, the peptide linker according to the invention is conjugated to a glycosylated IgG antibody. In one embodiment, the peptide linker is conjugated to a native glycosylated IgG antibody. Native IgG antibodies comprise a single conjugation site at glutamine residue 295 (Q295). Thus, in one embodiment the peptide linker is conjugated to residue Q295 of a native glycosylated antibody. The only glycosylation site of native IgG antibodies is asparagine residue 297 (N297). Thus, in a particular embodiment, the invention relates to the ADC / antibody-payload conjugate according to the invention, wherein the IgG antibody is glycosylated at residue N297 (EU numbering) of the CH2 domain. In a particular embodiment, the peptide linker is conjugated to position Q295 of an IgG antibody that is glycosylated at position N297. More preferably, the antibody is an IgG1 antibody. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the camptothecin is an exatecan or an exatecan derivative. As already outlined above, the cytotoxic molecule of the ADC of the present invention is a topoisomerase I inhibitor, e.g., a camptothecin. While numerous camptothecins are known in the art, including, for example, topotecan, exatecan, irinotecan, DX- 8951f, SN38, BN 80915, lurtotecan, 9-nitrocamptothecin and aminocamptothecin. In one embodiment, the camptothecin is an exatecan. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has an amino acid (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) residue linked to said topoisomerase I inhibitor (e.g., camptothecin cytotoxic molecule) of the second payload. Without being bound by theory, said amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) has the function of rendering the second payload not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has an amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) linked to said topoisomerase I inhibitor of the second payload, thereby rendering it not cell-permeable. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has an amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) as part of the linker which is linked to said topoisomerase I inhibitor of the second payload, thereby rendering it not cell- permeable upon releasing the corresponding amino acid-cytotoxic construct. The capability of a molecule (in the present case the topoisomerase I inhibitor) to be cell-permeable or not cell-permeable can be measured / determined by methods known in the art and as described herein. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has a glycine residue linked to said topoisomerase I inhibitor (preferably, said camptothecin cytotoxic molecule) of the second payload. Without being bound by theory, said glycine residue has the function of rendering the second payload not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has a glycine residue linked to said topoisomerase I inhibitor of the second payload, thereby rendering it not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has a glycine residue as part of the linker which is linked to said topoisomerase I inhibitor of the second payload, thereby rendering it not cell-permeable upon releasing the glycine-cytotoxic construct. The capability of a molecule (in the present case the topoisomerase I inhibitor) to be cell-permeable or not cell-permeable can be measured / determined by methods known in the art and as already described herein. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has an amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) linked to said camptothecin cytotoxic molecule of the second payload. Without being bound by theory, said amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) has the function of rendering the second payload not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has an amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) linked to said camptothecin cytotoxic molecule of the second payload, thereby rendering it not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has an amino acid residue (e.g., a glycine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine residue) as part of the linker which is linked to said camptothecin cytotoxic molecule of the second payload, thereby rendering it not cell- permeable upon releasing the corresponding amino acid-cytotoxic construct. The capability of a molecule (in the present case the camptothecin cytotoxic molecule) to be cell-permeable or not cell-permeable can be measured / determined by methods known in the art and as described herein. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload. Without being bound by theory, said glycine residue has the function of rendering the second payload not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload, thereby rendering it not cell-permeable. Thus, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the second payload has a glycine residue as part of the linker which is linked to said camptothecin cytotoxic molecule of the second payload, thereby rendering it not cell-permeable upon releasing the glycine-cytotoxic construct. The capability of a molecule (in the present case the camptothecin cytotoxic molecule) to be cell-permeable or not cell-permeable can be measured / determined by methods known in the art and as already described herein. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the antibody is an IgG antibody, in particular an IgG1 antibody. The terms “IgG antibody” and “IgG1 antibody” have already been described above. Asregards these definitions as well as embodiments thereof, same applies, mutatismutandis, as has been set forth above in the context of the ADC of the present invention. The present invention is not limited to a specific antibody, and the ADC may comprise any antibody, preferably any antibody that can be used in cancer therapy. In certain embodiments, the present invention relates to an ADC as defined herein, wherein the antibody is selected from the group consisting of: Trastuzumab, Brentuximab, , Gemtuzumab, Inotuzumab, Avelumab, Cetuximab, Rituximab, Daratumumab, Pertuzumab, Vedolizumab, Ocrelizumab, Tocilizumab, Ustekinumab, Golimumab, Obinutuzumab, Sacituzumab, Belantamab, Polatuzumab, Enfortumab, Endrecolomab, Gemtuzumab,Loncastuximab, Mecbotamab, Adecatumumab, D93, Gatipotuzumab, Labetuzumab, Tusamitamab, Upifitamab, Lifastuzumab, Mirvetuximab, Sofituzumab, Anetumab, Tisotumab, Cofituzumab, Praluzatamab, Ladriatuzumab, Belantamab, Patritumab, Cetuximab, Nimotuzumab, Matuzumab, Portuzumab, Citatuzumab, Tucotuzumab Endrecolomab and Indatuximab; and / or wherein the antibody specifically binds to an antigen selected from the group consistingof: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38, HER2, Integrin 4 7,CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA, CD79b, Nectin-4, EpCAM,CD33, CD19, AXL, dn-collagen, TA-MUC1, carcinoembryonic cell adhesion molecule5, CEACAM5, NaPi2b, FR , MUC16, mesothelin, TF, CD166, LIV-1, ERBB3, EGFR,TACSTD1, Claudin 18.2, CLDN1, CLDN6, CLDN9, EphA2, B7H4, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, Cadherin17, ST14, P-cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG-72, FGFRs (e.g., FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 (CD318), GPCR5A, GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4. The above antibodies are known in the art. In the following, it is indicated in brackets to which antigen said respective antibody specifically binds to: Trastuzumab (anti- Her2 / neu), Brentuximab (anti-CD30), Gemtuzumab (anti-CD33), Inotuzumab (anti- CD22), Avelumab (anti-PD-L1), Cetuximab (anti-EGFR), Rituximab (anti-CD20), Daratumumab (anti-CD38), Pertuzumab (anti-HER2), Vedolizumab (anti-Integrin 47), Ocrelizumab (anti-CD20), Tocilizumab (anti-IL-6-R), Ustekinumab (anti-IL-12 / 23), Golimumab (anti-TNF ), Obinutuzumab (anti-CD20), Sacituzumab (anti-Trop-2), Belantamab (anti-BCMA), Polatuzumab (anti-CD79b), Enfortumab (anti-Nectin-4), Endrecolomab (anti-EpCAM), Gemtuzumab (anti-CD33), Loncastuximab (anti-CD19), Mecbotamab (anti-AXL), Adecatumumab (anti-EpCAM), D93 (anti-dn-collagen), Gatipotuzumab (anti-TA-MUC1), Labetuzumab (anti-carcinoembryonic cell adhesion molecule 5), Tusamitamab (anti-CEACAM5), Upifitamab (anti-NaPi2b), Lifastuzumab(anti-NaPi2b), Mirvetuximab (anti-FR )), Sofituzumab (anti-MUC16), Anetumab (anti-mesothelin), Tisotumab (anti-TF), Cofituzumab (anti-Trop-2), Praluzatamab (anti- CD166), Ladriatuzumab (anti-LIV-1), Belantamab (anti-BCMA), Patritumab (anti- ERBB3), Cetuximab (anti-EGFR), Nimotuzumab (anti-EGFR), Matuzumab (anti- EGFR), Portuzumab (anti-HER2), Citatuzumab (anti-TACSTD1), Tucotuzumab (anti- EpCAM), Endrecolomab (anti-EpCAM) and Indatuximab (anti-CD138). In a particular embodiment, the present invention relates to an ADC as defined herein, wherein the antibody is Trastuzumab (anti-Her2 / neu). In an embodiment, the antibody is Trastuzumab with a heavy chain as set forth in SEQ ID NO:73 and a light chain as set forth in SEQ ID NO:74. In another embodiment, the antibody is an anti-Her2 / neu antibody with a heavy chain variable region as set forth in SEQ ID NO:102 and a light chain variable region as set forth in SEQ ID NO:103. In another embodiment, the antibody is an anti-Her2 / neu antibody with a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:104, a heavy chain CDR2 (CDR- H2, Kabat) as set forth in SEQ ID NO:105, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:106, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:107, a light chain CDR2 (CDR-L2, Kabat) as set forth in SEQ ID NO:108, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:109. In another particular embodiment, the present invention relates to an ADC as defined herein, wherein the antibody is Polatuzumab (anti-CD79b). In a embodiment, the antibody is Polatuzumab with a heavy chain as set forth in SEQ ID NO:71 and a light chain as set forth in SEQ ID NO:72. In another embodiment, the antibody is an anti-CD79b antibody with a heavy chain variable region as set forth in SEQ ID NO:110 and a light chain variable region as set forth in SEQ ID NO:111. In another embodiment, the antibody is an anti-CD79b antibody with a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:112, a heavy chain CDR2 (CDR- H2, Kabat) as set forth in SEQ ID NO:113, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:114, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:115, a light chain CDR2 (CDR-L2, Kabat) as set forth in SEQ ID NO:116, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:117. In another particular embodiment, the present invention relates to an ADC as defined herein, wherein the antibody is Enfortumab (anti-Nectin-4) or a variant thereof. In an embodiment, the antibody is Enfortumab with a heavy chain as set forth in SEQ ID NO:75 and a light chain as set forth in SEQ ID NO:95, 76 or 77. As outlined above, in a embodiment, the invention relates to the antibody-payload conjugate according to the invention, wherein the antibody is an antibody, preferably, an IgG antibody comprising at Kabat position 234 an A and / or at Kabat position 235 an A. Accordingly, in certain embodiments, the antibody is Enfortumab or a variant thereof comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:94. In certain embodiments, the anti-Nectin-4 antibody is Enfortumab comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:94 and a light chain as set forth in SEQ ID NO:95 or 76 or 77. In another embodiment, the antibody is an anti-Nectin-4 antibody with a heavy chain variable region as set forth in SEQ ID NO:118 and a light chain variable region as set forth in SEQ ID NO:119. In another embodiment, the antibody is an anti-Nectin-4 antibody with a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:120, a heavy chain CDR2 (CDR- H2, Kabat) as set forth in SEQ ID NO:121, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:122, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:123, a light chain CDR2 (CDR-L2, Kabat) as set forth in SEQ ID NO:124 or SEQ ID NO:142, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:125. In another particular embodiment, the present invention relates to an ADC as defined herein, wherein the antibody is m290 (anti-Nectin-4). In an embodiment, the antibody is m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97. In another embodiment, the antibody is an anti-Nectin-4 antibody with a heavy chain variable region as set forth in SEQ ID NO:126 and a light chain variable region as set forth in SEQ ID NO:127. In another embodiment, the antibody is an anti-Nectin-4 antibody with a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:128, a heavy chain CDR2 (CDR- H2, Kabat) as set forth in SEQ ID NO:129, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:130, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:131, a light chain CDR2 (CDR-L2, Kabat) as set forth in SEQ ID NO:132, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:133. In another particular embodiment, the present invention relates to an ADC as defined herein, wherein the antibody is Upifitamab (anti-NaPi2b). In a preferred embodiment, the antibody is Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99. As outlined above, in an embodiment, the invention relates to the antibody-payload conjugate according to the invention, wherein the antibody is an antibody, preferably, an IgG antibody comprising at Kabat position 234 an A and / or at Kabat position 235 an A. Accordingly, in certain embodiments, the antibody is Upifitamab comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:100. In certain embodiments, the anti-NaPi2b antibody is Upifitamab comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101. In another embodiment, the antibody is an anti-NaPi2b antibody with a heavy chain variable region as set forth in SEQ ID NO:134 and a light chain variable region as set forth in SEQ ID NO:135. In another embodiment, the antibody is an anti-NaPi2b antibody with a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:136, a heavy chain CDR2 (CDR- H2, Kabat) as set forth in SEQ ID NO:137, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:138, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:139, a light chain CDR2 (CDR-L2, Kabat) as set forth in SEQ ID NO:140, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:141. As mentioned, in certain embodiments, the present invention relates to an ADC as defined herein, wherein the antibody specifically binds to an antigen selected from the group consisting of: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38, HER2,Integrin 4 7, CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA, CD79b, Nectin-4, EpCAM, CD33, CD19, AXL, dn-collagen, TA-MUC1, carcinoembryonic celladhesion molecule 5, CEACAM5, NaPi2b, FR , MUC16,1, ERBB3, EGFR, TACSTD1, Claudin 18.2, CLDN1, CLDN6, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, P- cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG- FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4. In an embodiment, the present invention relates to an ADC as defined herein, wherein said ADC consists of two first payloads and two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”). Accordingly, in this embodiment, the peptide linker in accordance with the present invention comprises or contains 3 payloads, i.e., as a first payload a single topoisomerase I inhibitor which is cell- permeable; as a second payload a single topoisomerase I inhibitors which is not cell- permeable, and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin, e.g., an MMAE (Monomethyl auristatin E). Accordingly, in an embodiment, the peptide linker in accordance with the present invention comprises or contains 3 payloads, i.e., as a first payload a single camptothecin cytotoxic molecule which is cell- permeable; as a second payload a single camptothecin cytotoxic molecules which is not cell-permeable; and as a as a third payload an auristatin, e.g., an MMAE (Monomethyl auristatin E). Accordingly, in another embodiment, the peptide linker in accordance with the present invention comprises or contains 3 payloads, i.e., as a first payload an exatecan; as a second payload a G-Exa molecule; and as a as a third payload an MMAE (Monomethyl auristatin E). In a particular embodiment, the present invention relates to an ADC as defined herein having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a camptothecin cytotoxic molecule which is not cell-permeable; and a third payload as defined above, e.g., a toxin, e.g., anti-mitotic drug, tubulin polymerization-blocking agent, and / or auristatin, e.g., MMAE, wherein the cytotoxic molecule of the first and second payload is an exatecan; wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload; wherein said ADC consists of two first payloads and two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”); and wherein said antibody is and IgG, preferably, an IgG1 antibody. As regards the definitions of this ADC as well as embodiments thereof, same applies, mutatis mutandis, as has been set forth above in the context of the ADC of the present invention. In a particular embodiment, the present invention relates to an ADC as defined herein having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a camptothecin cytotoxic molecule which is not cell-permeable; and a third payload as defined above, e.g., a toxin, e.g., an anti-mitotic drug, tubulin polymerization-blocking agent, and / or auristatin, e.g., MMAE, wherein the cytotoxic molecule of the first and second payload is an exatecan; wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload; wherein said ADC consists of two first payloads and two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”); and wherein said antibody is Trastuzumab. As regards the definitions of this ADC as well as embodiments thereof, same applies, mutatis mutandis, as has been set forth above in the context of the ADC of the present invention. In a particular embodiment, the present invention relates to an ADC as defined herein having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a camptothecin cytotoxic molecule which is not cell-permeable; and a third payload as defined above, e.g., a toxin, e.g., an anti-mitotic drug, tubulin polymerization-blocking agent, and / or auristatin, e.g., MMAE, wherein the cytotoxic molecule of the first and second payload is an exatecan; wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload; wherein said ADC consists of two first payloads and two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”); and wherein said antibody is an antibody that specifically binds to the antigen NaPi2b. As regards the definitions of this ADC as well as embodiments thereof, same applies, mutatis mutandis, as has been set forth above in the context of the ADC of the present invention. In a particular embodiment, the present invention relates to an ADC as defined herein having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a camptothecin cytotoxic molecule which is not cell-permeable; and a third payload as defined above, e.g., a toxin, e.g., anti-mitotic drug, tubulin polymerization-blocking agent, and / or auristatin, e.g., MMAE, wherein the cytotoxic molecule of the first and second payload is an exatecan; wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload; wherein said ADC consists of two first payloads and two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”); and wherein said antibody is an antibody that specifically binds to the antigen Nectin-4, preferably wherein the antibody is m290 as defined herein. In the context of this particularly embodiment, in an even more particular embodiment, the linker comprises or consists of the following structure: In a particular embodiment, the present invention relates to an ADC comprising an antibody that specifically binds to the antigen Nectin-4, e.g., wherein the antibody comprises a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:128, a heavy chain CDR2 (CDR-H2, Kabat) as set forth in SEQ ID NO:129, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:130, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:131, a light chain CDR2 (CDR- L2, Kabat) as set forth in SEQ ID NO:132, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:133, or wherein the antibody comprises a heavy chain variable region as set forth in SEQ ID NO:126 and a light chain variable region as set forth in SEQ ID NO:127, or wherein the antibody comprises a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97; and a linker having the structure: wherein the linker is conjugated via the lysine residue to glutamine residue Q295 (EU numbering) of the heavy chain of the antibody. In a particular embodiment, the present invention relates to an ADC comprising an antibody that specifically binds to the antigen Nectin-4, e.g., wherein the antibody comprises a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:120, a heavy chain CDR2 (CDR-H2, Kabat) as set forth in SEQ ID NO:121, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:122, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:123, a light chain CDR2 (CDR- L2, Kabat) as set forth in SEQ ID NO:124 or SEQ ID NO:142, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:125, or wherein the antibody comprises a heavy chain variable region as set forth in SEQ ID NO:118 and a light chain variable region as set forth in SEQ ID NO:119, or wherein the antibody comprises a heavy chain as set forth in SEQ ID NO:75 and a light chain as set forth in SEQ ID NO:95, 76 or 77; and a linker having the structure: wherein the linker is conjugated via the lysine residue to glutamine residue Q295 (EU numbering) of the heavy chain of the antibody. In a particular embodiment, the present invention relates to an ADC comprising an antibody that specifically binds to the antigen Nectin-4, e.g., wherein the antibody comprises a heavy chain CDR1 (CDR-H1, Kabat) as set forth in SEQ ID NO:120, a heavy chain CDR2 (CDR-H2, Kabat) as set forth in SEQ ID NO:121, a heavy chain CDR3 (CDR-H3, Kabat) as set forth in SEQ ID NO:122, a light chain CDR1 (CDR-L1, Kabat) as set forth in SEQ ID NO:123, a light chain CDR2 (CDR- L2, Kabat) as set forth in SEQ ID NO:124 or SEQ ID NO:142, and a light chain CDR3 (CDR-L3, Kabat) as set forth in SEQ ID NO:125, or wherein the antibody comprises a heavy chain variable region as set forth in SEQ ID NO:118 and a light chain variable region as set forth in SEQ ID NO:119, or wherein the antibody comprises a heavy chain as set forth in SEQ ID NO:94 and a light chain as set forth in SEQ ID NO:95, 76 or 77; and a linker having the structure:

[0003] wherein the linker is conjugated via the lysine residue to glutamine residue Q295 (EU numbering) of the heavy chain of the antibody. As regards the definitions of this ADC as well as embodiments thereof, same applies, mutatis mutandis, as has been set forth above in the context of the ADC of the present invention. The ADC of the present invention is particularly useful in medical settings. In one embodiment, the present invention relates to a pharmaceutical composition comprising the ADC as defined herein and at least one pharmaceutically acceptable ingredient. The term "pharmaceutical composition" as used herein refers to any composition comprising a chemical substance or active ingredient which composition is intended for use in the medical cure, treatment, or prevention of disease and which is in such a form as to permit the active ingredient to be effective. In particular, a pharmaceutical composition does not contain excipients which are unacceptably toxic to a subject to which the composition is to be administered. The pharmaceutical compositions are sterile, i.e., aseptic and free from all living microorganisms and their spores. The pharmaceutical composition of the present invention is preferably liquid. The pharmaceutical composition according to the invention comprises an antibody- drug conjugate as disclosed herein. Pharmaceutical compositions comprising an antibody-drug conjugate are preferably used for the treatment of diseases. The pharmaceutical composition according to the invention may comprise at least one pharmaceutically acceptable ingredient. A pharmaceutically acceptable ingredient refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to a subject. A pharmaceutically acceptable ingredient includes, but is not limited to, a buffer, excipient, stabilizer, or preservative. Pharmaceutical formulations of the antibody-payload conjugates described herein are prepared by mixing such conjugates having the desired degree of purity with one or more optional pharmaceutically acceptable ingredients (Flemington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Pharmaceutically acceptable ingredients are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m- cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG). Exemplary pharmaceutically acceptable ingredients herein further include insterstitial drug dispersion agents such as soluble neutral-active hyaluronidase glycoproteins (sHASEGP), for example, human soluble PH-20 hyaluronidase glycoproteins, such as rHuPH20 (HYLENEX®, Baxter International, Inc.). Certain exemplary sHASEGPs and methods of use, including rHuPH20, are described in US Patent Publication Nos. 2005 / 0260186 and 2006 / 0104968. For example, a sHASEGP may be combined with one or more additional glycosaminoglycanases such as chondroitinases. In a particular embodiment, the invention relates to a pharmaceutical composition according to the invention comprising at least one additional therapeutically active agent. The pharmaceutical composition comprising the antibody-payload conjugate may comprise one or more additional therapeutically active agents. It is to be understood that the antibody-payload conjugates may be used in various therapeutic areas. As such, the additional therapeutically active agent in the pharmaceutical composition may vary depending on the use of the pharmaceutical composition. In certain embodiments, as outlined in more detail further below, a pharmaceutical composition comprising an antibody-payload conjugate according to the invention may be used in the treatment of a neoplactic disorder, preferably in the treatment of cancer. In such embodiment, the pharmaceutical composition may comprise one or more additional anti-cancer drugs. The term “anti-cancer” drug is used herein to refer to one or a combination of drugs conventionally used to treat cancer. For example, a pharmaceutical composition comprising an antibody-payload conjugate according to the invention may further comprise one or more chemotherapeutic agents. As used herein, the term “chemotherapeutic agent” or “chemotherapy agent” or “chemotherapeutic drug” refer to an agent that reduces, prevents, mitigates, limits, and / or delays the growth of metastases or neoplasms, or kills neoplastic cells directly by necrosis or apoptosis of neoplasms or any other mechanism, or that can be otherwise used, in a pharmaceutically-effective amount, to reduce, prevent, mitigate, limit, and / or delay the growth of metastases or neoplasms in a subject with neoplastic disease. Chemotherapeutic agents include, for example, fluoropyrimidines; pyrimidine nucleosides; purine nucleosides; anti-folates, platinum agents; anthracyclines / anthracenediones; epipodophyllotoxins; camptothecins; hormones; hormonal complexes; antihormonals; enzymes, proteins, peptides and polyclonal and / or monoclonal antibodies; vinca alkaloids; taxanes; epothilones; antimicrotubule agents; alkylating agents; antimetabolites; topoisomerase inhibitors; antivirals; and various other cytotoxic and cytostatic agents. In a particular embodiment, the invention relates to the antibody-payload conjugate according to the invention, or the pharmaceutical composition according to the invention for use in therapy. Thus, the antibody-payload conjugate or the pharmaceutical composition according to the invention may be used in the treatment of a subject / patient. An individual or subject or patient is preferably a mammal. Mammals include, but are not limited to, domesticated animals (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as macaques), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the individual or subject is a human. A “subject in need” is typically one who is suffering from, has been diagnosed with, or is at risk of developing a neoplastic disease, such as cancer, or for whom administration of the antibody-payload conjugate or pharmaceutical composition is indicated for the prevention, treatment, or management of such disease. In one embodiment, the present invention relates to an ADC as defined herein, for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease. A neoplastic disease or a neoplasm is commonly understood, in its broadest sense, as a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. This abnormal growth usually forms a mass, when it may be called a tumour or tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers. A neoplasm can be benign, potentially malignant, or malignant (cancer). The patient suffering from cancer may be a patient who has not been previously treated with any anti-cancer therapy. However, the patient suffering from cancer may also be a patient who was refractory to a previous anti-cancer treatment. The term “neoplastic disease” as used herein refers to a condition characterized by uncontrolled, abnormal growth of cells. Neoplastic diseases include cancer. Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia. More particular examples of such cancers include breast cancer, prostate cancer, colon cancer, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, liver cancer, bladder cancer, hepatoma, colorectal cancer, uterine cervical cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, vulval cancer, thyroid cancer, hepatic carcinoma, skin cancer, melanoma, brain cancer, ovarian cancer, neuroblastoma, myeloma, various types of head and neck cancer, acute lymphoblastic leukemia, acute myeloid leukemia, Ewing sarcoma and peripheral neuroepithelioma. Preferred cancers include liver cancer, ovarian cancer, non-small cell lung cancer, colorectal cancer, pancreatic cancer, lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, Ewing sarcoma and peripheral neuroepithelioma. The antibody-payload conjugates according to the invention may be used for the treatment of cancer. As such, in certain embodiments, the antibody-payload conjugates according to invention comprise an antibody that specifically binds to an antigen that is present on a tumor cell. In certain embodiments, the antigen may be an antigen on the surface of a tumor cell. In certain embodiments, the antigen on the surface of the tumor cell may be internalized into the cell together with the antibody- payload conjugate upon binding of the antibody-payload conjugate to the antigen. In one embodiment, the present invention relates to an ADC as defined herein or the pharmaceutical composition as defined herein, wherein the antibody-payload conjugate comprises Trastuzumab and wherein the neoplastic disease is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; wherein the antibody-payload conjugate comprises Polatuzumab and wherein the neoplastic disease is a B-cell associated cancer; e.g., wherein the B-cell associated cancer is non-Hodgkin lymphoma, in particular wherein the B-cell associated cancer is diffuse large B-cell lymphoma; or wherein the antibody-payload conjugate comprises Enfortumab or an Enfortumab variant, or m290, and wherein the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer; or wherein the antibody-payload conjugate comprises Upifitamab and wherein the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer. Thus, in certain embodiments, the antibody-payload conjugate and / or the pharmaceutical composition according to the invention may be used in the treatment of HER2-positive cancers. That is, in a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate comprises Trastuzumab and wherein the neoplastic disease is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer. For this embodiment, the antibody-payload conjugate may comprise an anti-HER2 / neu antibody as disclosed herein, preferably wherein the anti- HER2 / neu antibody is internalized into a target cell upon binding to HER2 / neu. In certain embodiments, the anti-HER2 / neu antibody is Trastuzumab with a heavy chain as set forth in SEQ ID NO:73 and a light chain as set forth in SEQ ID NO:74. In certain embodiments, the anti-HER2 / neu antibody comprised in the antibody- payload conjugate or the pharmaceutical composition may be the linker shown in Figure 8 or any one of the linkers disclosed herein. A HER2-positive cancer, as used herein, may be, without limitation HER2-positive breast, gastric, ovarian or lung cancer. The skilled person is able to determine whether a cancer is a HER2-positve cancer. For example, tumor cells may be isolated in a biopsy and the presence of HER2 / neu may be determined with any method known in the art. Further, the anti-HER2 / neu antibody-payload conjugate and / or the pharmaceutical composition comprising an anti-HER2 / neu antibody-payload conjugate may be used in conjunction with other therapies that are suitable for the treatment of HER2-positive cancers. Thus, in a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate or the pharmaceutical composition is administered in combination with lapatinib, capecitabine and / or a taxane. It is to be understood that the antibody-payload conjugate or the pharmaceutical composition does not necessarily have to be administered at the same time as the additional therapeutic agent, such as lapatinib, capecitabine and / or a taxane. Instead the antibody-payload conjugate or the pharmaceutical composition may be administered with a different administration schedule and, consequently, on different days as other therapeutic agents that are used for the treatment of the same disease. In certain embodiments, the antibody-payload conjugate and / or the pharmaceutical composition according to the invention may be used in the treatment of B-cell- associated cancer. Thus, in a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate comprises Polatuzumab and wherein the neoplastic disease is a B-cell associated cancer. For this embodiment, the antibody-payload conjugate may comprise an anti-CD79b antibody as disclosed herein, preferably wherein the anti-CD79b antibody is internalized into a target cell upon binding to CD79b. In certain embodiments, the anti- CD79b antibody is Polatuzumab with a heavy chain as set forth in SEQ ID NO:71 and a light chain as set forth in SEQ ID NO:72. In certain embodiments, the anti-CD79b antibody comprised in the antibody-payload conjugate or the pharmaceutical composition may be conjugated to the linker shownin Figure 8 or any one of the linkers disclosed herein.A B-cell associated cancer may be any one selected from a group consisting of: high, intermediate and low grade lymphomas (including B cell lymphoma such as, for example, mucosa-associated lymphoid tissue B cell lymphoma and non-Hodgkin’s lymphoma(NHL), mantle cell lymphoma, Burkitt's lymphoma, small lymphocytic lymphoma, marginal Zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, and Hodgkin’s lymphoma and T cell lymphomas) and leukemias (including secondary leukemia, chronic lymphocytic leukemia(CLL), such as B cell leukemia (CD5+ B lymphocytes), myeloid leukemia, such as acute myeloid leukemia, chronic myeloid leukemia, lymphoid leukemia, such as acute lymphoblastic leukemia (ALL) and myelodysplasia), and other hematological and / or B cell – or T-cell- associated cancers, including cancers of additional hematopoietic cells, including polymorphonuclear leukocytes, such as basophils, eosinophils, neutrophils and monocytes, dendritic cells, platelets, erythrocytes and natural killer cells. Also included are cancerous B cell proliferative disorders selected from the following: lymphoma, non-Hodgkins lymphoma(NHL) aggressive NHL, relapsed aggressive NHL, relapsed indolent NHL, refractory NHL, refractory indolent NHL, chronic lymphocytic leukemia (CLL), Small lymphocytic lymphoma, leukemia, hairy cell leukemia(HCL), acute lymphocytic leukemia (ALL), and mantle cell lymphoma. In a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the B-cell associated cancer is non-Hodgkin lymphoma, in particular wherein the B-cell associated cancer is diffuse large B-cell lymphoma. Further, the anti-CD79b antibody-payload conjugate and / or the pharmaceutical composition comprising an anti-CD79b antibody-payload conjugate may be used in conjunction with other therapies that are suitable for the treatment of B-cell-associated cancer. Thus, in a particular embodiment the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate or the pharmaceutical composition is administered in combination with bendamustine and / or rituximab. It is to be understood that the antibody-payload conjugate or the pharmaceutical composition does not necessarily have to be administered at the same time as the additional therapeutic agent, such as bendamustine and / or rituximab. Instead, the antibody-payload conjugate or the pharmaceutical composition may be administered with a different administration schedule and, consequently, on different days as other therapeutic agents that are used for the treatment of the same disease. In certain embodiments, the antibody-payload conjugate and / or the pharmaceutical composition according to the invention may be used in the treatment of Nectin-4- positive cancers. That is, in a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate comprises Enfortumab or an Enfortumab variant, or m290, and wherein the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer. For this embodiment, the antibody-payload conjugate may comprise an anti-Nectin-4 antibody as disclosed herein, e.g., wherein the anti- Nectin-4 antibody is internalized into a target cell upon binding to Nectin-4. In certain embodiments, the anti-Nectin-4 antibody is Enfortumab with a heavy chain as set forth in SEQ ID NO:75 and a light chain as set forth in SEQ ID NO:95, 76 or 77. Moreover, as outlined above, in one embodiment, the invention relates to the antibody- payload conjugate according to the invention, wherein the antibody is an antibody, e.g., an IgG antibody comprising at Kabat position 234 an A and / or at Kabat position 235 an A. Accordingly, in certain embodiments, the antibody is Enfortumab or a variant thereof comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:94. In certain embodiments, the antibody is Enfortumab comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:94 and a light chain as set forth in SEQ ID NO:95. In certain other embodiments, the present invention relates to an ADC as defined herein, wherein the antibody is m290 (anti-Nectin-4). In one embodiment, the antibody is m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97. In certain embodiments, the anti-Nectin-4 antibody comprised in the antibody-payload conjugate or the pharmaceutical composition may be conjugated to the linker shownin Figure 8 or any one of the linkers disclosed herein. In a preferred embodiment, theanti-Nectin-4 antibody, in particular the anti-Nectin-4 antibody m290, may beconjugated to the linker shown in Figure 8.A Nectin-4-positive cancer, as used herein, may be, without limitation Nectin-4-positive pancreatic cancer, lung cancer, bladder cancer or breast cancer. The skilled person is able to determine whether a cancer is a Nectin-4-positve cancer. For example, tumor cells may be isolated in a biopsy and the presence of Nectin-4 may be determined with any method known in the art. The anti-Nectin-4 antibody-payload conjugate and / or the pharmaceutical composition comprising an anti-Nectin-4 antibody-payload conjugate according to the invention may be administered alone in patients who have previously received a PD-1 or PD-L1 inhibitor in combination with a platinum-based chemotherapeutic agent before or after surgery. Further, the anti-Nectin-4 antibody-payload conjugate and / or the pharmaceutical composition comprising an anti-Nectin-4 antibody-payload conjugate may be used in conjunction with other therapies that are suitable for the treatment of Nectin-4-positive cancers. Thus, in a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate or the pharmaceutical composition is administered in combination with a platinum-based chemotherapeutic agent and / or Pembrolizumab. It is to be understood that the antibody-payload conjugate or the pharmaceutical composition does not necessarily have to be administered at the same time as the additional therapeutic agent, such as the cisplatin-based chemotherapeutic agent and / or Pembrolizumab. Instead the antibody-payload conjugate or the pharmaceutical composition may be administered with a different schedule and, consequently, on different days as other therapeutic agents that are used for the treatment of the same disease. In certain embodiments, the antibody-payload conjugate and / or the pharmaceutical composition according to the invention may be used in the treatment of NaPi2b- positive cancers. That is, in a particular embodiment, the invention relates to the antibody-payload conjugate or the pharmaceutical composition for use according to the invention, wherein the antibody-payload conjugate comprises Upifitamab, and wherein the neoplastic disease is an anti-NaPi2b positive cancer. For this embodiment, the antibody-payload conjugate may comprise an anti-NaPi2b antibody as disclosed herein, e.g., wherein the anti-NaPi2b antibody is internalized into a target cell upon binding to NaPi2b. In a preferred embodiment, the antibody is Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99. As outlined above, in one embodiment, the invention relates to the antibody-payload conjugate according to the invention, wherein the antibody is an antibody, preferably, an IgG antibody comprising at Kabat position 234 an A and / or at Kabat position 235 an A. Accordingly, in certain embodiments, the antibody is Upifitamab comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:100. In certain embodiments, the antibody is Upifitamab comprising at Kabat position 234 an A and at Kabat position 235 an A with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101. In certain embodiments, the anti-NaPi2b antibody comprised in the antibody-payload conjugate or the pharmaceutical composition may be conjugated to the linker shownin Figure 8 or any one of the linkers disclosed herein.A NaPi2b-positive cancer, as used herein, may be, without limitation NaPi2b-positive lung or ovarian cancer. The skilled person is able to determine whether a cancer is a NaPi2b-positve cancer. For example, tumor cells may be isolated in a biopsy and the presence of NaPi2b may be determined with any method known in the art. In a particular embodiment, the invention relates to a use of the antibody-payload conjugate according to the invention, or the pharmaceutical composition according to the invention for the manufacture of a medicament for the treatment of a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease. As regards the embodiments of the use of the antibody-payload conjugate according to the invention, or the pharmaceutical composition according to the invention for the manufacture of a medicament for the treatment of a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease, the same applies, mutatis mutandis, as has been set forth above in the context of the composition or the pharmaceutical composition for uses as defined above. The antibody-payload conjugate or the pharmaceutical composition according to the invention may be administered by any suitable means, including parenteral, intrapulmonary, and intranasal, and, if desired for local treatment, intralesional, intrauterine or intravesical administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. Dosing can be by any suitable route, e.g., by injections, such as intravenous or subcutaneous injections, depending in part on whether the administration is brief or chronic. Various dosing schedules including but not limited to single or multiple administrations over various time-points, bolus administration, and pulse infusion are contemplated herein. The antibody-payload conjugate or the pharmaceutical composition according to the invention may be formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The antibody-payload conjugate or the pharmaceutical composition according to the invention need not be, but is optionally formulated with one or more agents currently used to prevent or treat the disorder in question. The effective amount of such other agents depends on the amount of antibody-payload conjugate present in the formulation, the type of disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as described herein, or about from 1 to 99% of the dosages described herein, or in any dosage and by any route that is empirically / clinically determined to be appropriate. For the prevention or treatment of disease, the appropriate dosage of the antibody- payload conjugate or the pharmaceutical composition according to the invention (when used alone or in combination with one or more other additional therapeutic agents) will depend on the type of disease to be treated, the type of antibody-payload conjugate, the severity and course of the disease, whether the antibody-linker conjugate is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the antibody-linker conjugate, and the discretion of the attending physician. The antibody-payload conjugate or the pharmaceutical composition according to the invention is suitably administered to the patient at one time or over a series of treatments. The invention also relates to methods of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease, wherein the ADC or the pharmaceutical composition of the present invention as defined herein is administered to a subject, preferably, in a therapeutically effective amount as defined herein.As regards the embodiments of the methods for treatment the same applies, mutatismutandis, as has been set forth above in the context of the composition or the pharmaceutical composition for uses as defined above. Another aspect of the present invention relates to the linker as such, in particular the peptide linkers disclosed herein. That is, in a particular embodiment, the invention relates to a linker comprising a first, second and third payload, wherein the first payload is a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; wherein the second payload a topoisomerase I inhibitor which is not cell-permeable, e.g.,, a camptothecin cytotoxic molecule which is not cell-permeable; and wherein the third payload is a toxin or a cytotoxin, e.g., an auristatin, e.g., an MMAE (Monomethyl auristatin E); optionally wherein the linker is for conjugation to an antibody In another embodiment, the invention relates to a linker according to the invention, wherein the camptothecin is exatecan or DXd. In another embodiment, the invention relates to a linker according to the invention, wherein the second payload has been modified to reduce its cell permeability. In another embodiment, the invention relates to a linker according to the invention, wherein the second payload has a glycine residue linked to said topoisomerase I inhibitor of the second payload. In another embodiment, the invention relates to a linker according to the invention, wherein the linker is a peptide linker. In another embodiment, the invention relates to a linker according to the invention, wherein the first payload and / or second payload are linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker; e.g., wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker, or vice versa. In another embodiment, the invention relates to a linker according to the invention, wherein the linker comprises a primary amine for conjugation to an antibody, e.g., wherein the primary amine is comprised in a lysine residue, a lysine mimetic or a lysine derivative; or wherein the primary amine is comprised in an amino acid residue having the structure NH2-(CH2)1-10-COOH; e.g., wherein the amino acid residues are comprised in a peptide linker. In another embodiment, the invention relates to a linker according to the invention, wherein the linker further comprises at least one positively charged amino acid residue, e.g., wherein the at least one positively charged amino acid residue is selected from arginine and / or histidine. In another embodiment, the invention relates to a linker according to the invention, wherein the linker comprises the following structure: [payload1]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 2]; or [payload2]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2; and X is either absent or a self-immolative group, e.g., PABC. In another embodiment, the invention relates to a linker according to the invention, wherein (Aa)m+ (Aa)n+ (Aa)ois > 0, e.g., wherein (Aa)n+ (Aa)ois > 0. In another embodiment, the invention relates to a linker according to the invention, wherein Z2is a dicarboxylic acid linking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and wherein one payload is directly or indirectly linked to the C- terminal end of (Aa)mand the other payload is directly or indirectly linked to the C- terminal end of (Lys) or (Aa)o, or vice versa. In another embodiment, the invention relates to a linker according to the invention, wherein the linker comprises the following structure: [payload1]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 2]; or [payload2]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m is an integer ranging from 1 to 10, e.g., 1 to 6 or 1 to 4; n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mto the N- terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, e.g., PABC. In another embodiment, the invention relates to a linker according to the invention, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction). In another embodiment, the invention relates to a linker according to the invention,wherein (Aa)n-(Lys)-(Aa)o is or comprises RK or RKAA (in N -> C direction).In another embodiment, the invention relates to a linker according to the invention, wherein the linker is a peptide linker and wherein the third payload is linked to the N- or C-terminus of the peptide linker or wherein the third payload is linked to a side chain of an amino acid residue comprised in the peptide linker. In another embodiment, the invention relates to a linker according to the invention, wherein two payloads are linked to the same functional group of the peptide linker, preferably via a chemical linker comprising a disubstituted amine. In another embodiment, the invention relates to a linker according to the invention, wherein the linker consists of or comprises the structure: ([payload]-X-Z1-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-Z2-(Aa)n(Lys)-(Aa)o-Z3-X-[payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X- ( - (Aa)p / p*-Z3-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, e.g., wherein the spacer comprises (CH2)2, e.g., wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, e.g., PABC. In another embodiment, the invention relates to a linker according to the invention, wherein (Aa)n+ (Aa)ois > 0. In another embodiment, the invention relates to a linker according to the invention, wherein the linker consists of or comprises the structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X- [payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-X- [payload])2;or ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N- ((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, e.g., 1 to 6 or 1 to 4; n and o may be integers ranging from 0 to 10, e.g., 0 to 6 or 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, e.g., PABC. In another embodiment, the invention relates to a linker according to the invention, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction). In another embodiment, the invention relates to a linker according to the invention, wherein (Aa)n-(Lys)-(Aa)o is or comprises RK or RKAA (in N -> C direction).In another embodiment, the invention relates to a linker according to the invention, wherein the linker comprises or consists of the following structure: As regards the exact composition of the linker as well as embodiments thereof, same applies, mutatis mutandis, as has been set forth above in the context of the ADC of thepresent invention. Another aspect of the present invention relates to a method for the preparation of the ADC according to the invention. ADCs may the prepared using the methods disclosed in WO 2023 / 161291, which is fully incorporated herein by reference. In a particular embodiment, the invention relates to a method for the preparation of an antibody-drug conjugate comprising a step of conjugating a peptide linker according to the invention to an antibody. That is, any of the peptide linkers comprising at least a first and second topoisomerase I inhibitor and a third payload as disclosed herein may be conjugated to an antibody. In particular, any of the amine-comprising peptide linkers disclosed herein may be conjugated to a glutamine residue of an antibody via a transglutaminase. As disclosed elsewhere herein, the glutamine residue to which the peptide linker is conjugated may be an endogenous glutamine residue (e.g., Q295 of an IgG antibody) or may be a glutamine residue that has been introduced into the antibody by molecular engineering. In a particular embodiment, the invention relates to a method for the conjugation of a peptide linker according to the invention using a transglutaminase (TG), the method comprising a) mixing the antibody, the peptide linker and a transglutaminase (TG) within a fluid, thereby conjugating the linker-payload to the antibody in one step under the catalyzing effect of the TG, and b) extracting the conjugate obtained in step a) from the fluid. Accordingly, the present invention further encompasses methods for conjugating peptide linkers according to the invention to an antibody by means of a transglutaminase in a one-step reaction. For that, an antibody may be mixed with the peptide linker according to the invention and a transglutaminase within a fluid. A “fluid”, within the meaning of the present invention is a liquid. In certain embodiments, the liquid is an aqueous solution, e.g., a buffered aqueous solution. The peptide linker according to the invention may be mixed with the antibody and the transglutaminase by mixing a solution comprising said peptide linker with a solution comprising an antibody and a solution comprising the transglutaminase. Alternatively, solutions individually comprising the peptide linker, the antibody and the transglutaminase may be added to an aqueous solution. In particular, each component may be added to the aqueous solution at a defined concentration. The peptide linker according to the invention is conjugated to the antibody under the catalyzing effect of the transglutaminase. That is, the individual components may be mixed under conditions that are suitable for an efficient conjugation of the peptide linker to the antibody. Such conditions are defined elsewhere herein. In a second method step, the obtained antibody-payload conjugates have to be removed from the liquid. The skilled person is aware of methods to isolate antibody- payload conjugates from an aqueous solution. Further, the skilled person is aware of methods to separate antibody-payload conjugates from unconjugated antibodies or peptide linkers or from incompletely conjugated antibodies. For example, antibody payload conjugates according to the invention may be isolated from the mixture by HPLC. It is to be understood that “extracting the conjugate from the fluid” is synonymous with “isolating the conjugate from the mixture”. That is, a conjugate may also be extracted by removing the transglutaminase and unconjugated antibody and peptide linker from the fluid. The peptide linker that is used in the method according to the invention may be any one of the peptide linkers disclosed herein, in particular any peptide linker falling within the definition provided herein above or any peptide linker shown in the experimental examples. Thus, in a particular embodiment, the invention relates to the method according to the invention, wherein the peptide linker is the peptide linker of the invention. Further, the antibody may be an antibody as defined in more detail elsewhere herein, i.e., for the antibody-payload conjugate according to the invention. In particular, the peptide linker may comprise an amino acid sequence as set forth in SEQ ID NOs:1-29 or 82-93. Furthermore, the linker may be any one of the linkers shown in FIGs.4, 6, 7 or 8. That is, in a particular embodiment, the invention relates to the method according to the invention, wherein the peptide linker is conjugated to a glutamine residue comprised in the antibody via a primary amine comprised in an amino acid residue of the peptide linker. In a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is an antibody fragment, as defined elsewhere herein. In a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is an IgA, IgD, IgE, IgG or IgM antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the peptide linker is conjugated to a glutamine residue comprised in an Fc domain of the antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the glutamine residue to which the peptide linker is conjugated is glutamine residue Q295 (EU numbering) of the CH2 domain of an IgG antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the glutamine residue to which the peptide linker is conjugated has been introduced into the heavy or light chain of the antibody by molecular engineering. In a particular embodiment, the invention relates to the method according to the invention, wherein the glutamine residue that has been introduced into the heavy or light chain of the antibody by molecular engineering is N297Q (EU numbering) of the CH2 domain of an aglycosylated IgG antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the glutamine residue that has been introduced into the heavy or light chain of the antibody by molecular engineering is comprised in a peptide that has been (a) integrated into the heavy or light chain of the antibody or (b) fused to the N- or C-terminal end of the heavy or light chain of the antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the peptide comprising the Gln residue has been fused to the C- terminal end of the heavy chain of the antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is a glycosylated IgG antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the IgG antibody is glycosylated at residue N297 (EU numbering) of the CH2 domain. In a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is selected from the group consisting of: m290, Trastuzumab, Brentuximab, , Gemtuzumab, Inotuzumab, Avelumab, Cetuximab, Rituximab, Daratumumab, Pertuzumab, Vedolizumab, Ocrelizumab, Tocilizumab, Ustekinumab, Golimumab, Obinutuzumab, Sacituzumab, Belantamab, Polatuzumab, Enfortumab, Endrecolomab, Gemtuzumab,Loncastuximab, Mecbotamab, Adecatumumab, D93, Gatipotuzumab, Labetuzumab, Tusamitamab, Upifitamab, Lifastuzumab, Mirvetuximab, Sofituzumab, Anetumab, Tisotumab, Cofituzumab, Praluzatamab, Ladriatuzumab, Belantamab, Patritumab, Cetuximab, Nimotuzumab, Matuzumab, Portuzumab, Citatuzumab, Tucotuzumab, Endrecolomab and Indatuximab; and / or wherein the antibody specifically binds to an antigen selected from the group consistingof: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38, HER2, Integrin 4 7,CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA, CD79b, Nectin-4, EpCAM,CD33, CD19, AXL, dn-collagen, TA-MUC1, carcinoembryonic cell adhesion molecule5, CEACAM5, NaPi2b, FR , MUC16, mesothelin, TF, CD166, LIV-1, ERBB3, EGFR,TACSTD1, Claudin 18.2, CLDN1, CLDN6, CLDN9, EphA2, B7H4, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, Cadherin17, ST14, P-cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG-72, FGFRs (e.g., FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 (CD318), GPCR5A, GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4. In a particular embodiment, the invention relates to the method according to theinvention, wherein the peptide linker is conjugated to a -carboxamide group of a Glnresidue comprised in the antibody. In a particular embodiment, the invention relates to the method according to the invention, wherein the peptide linker is suitable for conjugation to a glycosylated antibody with a conjugation efficiency of at least 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90% or 95%. That is, in certain embodiments, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 70%. In another embodiment, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 75%. In another embodiment, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 80%. In another embodiment, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 85%. In another embodiment, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 90%. In another embodiment, the peptide linker according to the invention may be conjugated to a glycosylated antibody with an efficiency of at least 95%. In certain embodiments, the glycosylated antibody is a glycosylated IgG antibody, e.g., an IgG antibody that is glycosylated at residue N297 (EU numbering). The skilled person is aware of methods to determine the conjugation efficiency of an antibody with a specific peptide linker. For example, the conjugation efficiency may be determined as described herein. That is, an antibody, in particular an IgG1 antibody, may be incubated at a concentration of 1-5 mg / mL with 5-20eq molar equivalents of a linker and 3-6 U of a microbial transglutaminase per mg of antibody in a suitable buffer for 20-48 hours at 37°C or as described in Example 1. After the incubation period, the conjugation efficiency may be determined by LC-MS analysis under reducingconditions. The microbial transglutaminase may be an MTG from Streptomycesmobaraensis that is, for example, available from Zedira (Germany). A suitable buffermay be a Tris, MOPS, HEPES, PBS or BisTris buffer. However, it is to be understood that the choice of the buffer system may vary and depend to a large extent on the chemical properties of the linker. However, the skilled person is capable of identifying the optimal buffer conditions based on the disclosure of the present invention. Alternatively, the conjugation efficiency may be determined as described in Spycher et al. (Dual, Site-Specific Modification of Antibodies by Using Solid-Phase Immobilized Microbial Transglutaminase, ChemBioChem 201918(19):1923-1927) and analyzed as in Benjamin et al. (Thiolation of Q295: Site-Specific Conjugation of Hydrophobic Payloads without the Need for Genetic Engineering, Mol. Pharmaceutics 2019, 16: 2795-2807). In certain embodiments, antibodies may be conjugated by incubating 5 mg / ml of native, glycosylated monoclonal antibody for 24 hours at 37°C in 50 mM Tris pH 7.6 with a microbial transglutaminase (MTG, Zedira) at a concentration of 5-10 U / mg antibody and 5 molar equivalents of the indicated linker-payload in a rotating thermomixer. However, it is to be understood that the conditions, in particular the buffer conditions and the peptide linker concentration may be adjusted depending on the properties of the payload(s). However, the skilled person is able to identify the optimal reaction conditions based on the teaching provided herein. In a particular embodiment, the invention relates to the method according to the invention, wherein the transglutaminase is a microbial transglutaminase (MTG). The transglutaminase for use in the method of the present invention may be any transglutaminase that is suitable for conjugating the peptide linker of the invention to an antibody. The transglutaminase may be of any origin, e.g., the transglutaminase may be of bacterial, archaeal or eukaryotic origin. In certain embodiments, the transglutaminase may be a mammalian transglutaminase, including human transglutaminases. In certain embodiments, the transglutaminase may be a microbial transglutaminase, including bacterial and fungal transglutaminases. In a particular embodiment, the invention relates to the method according to theinvention, wherein the microbial transglutaminase is derived from a Streptomycesspecies, in particular Streptomyces mobaraensis.That is, the microbial transglutaminase used in the method of the invention may bederived from a Streptomyces species, in particular from Streptomyces mobaraensis,preferentially with a sequence identity of 80% to the native enzyme. Accordingly, the MTG may be a native enzyme or may be an engineered variant of a native enzyme. One such microbial transglutaminase is commercially available from Zedira(Germany). It is recombinantly produced in E. coli. Streptomyces mobaraensistransglutaminase has an amino acid sequence as disclosed in SEQ ID NO:78. S.mobaraensis MTG variants with other amino acid sequences have been reported and are also encompassed by this invention (SEQ ID NO:79 and 80).One such microbial transglutaminase could also be the MTG-TX variant from S.mobaraensis described in Jin et al.2016, Journal of Molecular Catalysis B: Enzymatic,which exhibits high-salt-resistance and a broad range of pH and temperature stability.In another embodiment, a microbial transglutaminase from Streptomyces ladakanum(formerly known as Streptoverticillium ladakanum) may be used. Streptomycesladakanum transglutaminase (US Pat No US 6,660,510 B2) has an amino acid sequence as disclosed in SEQ ID NO:81. Both of the above transglutaminases may be sequence modified. In several embodiments, transglutaminases may be used which have 80%, 85%, 90% or 95% or more sequence identity with any one of SEQ ID NO:78 - 81. Another suitable microbial transglutaminase is commercially from Ajinomoto, called ACTIVA TG. In comparison to the transglutaminase from Zedira, ACTIVA TG lacks 4 N-terminal amino acids, but has similar activity. Further microbial transglutaminases which may be used in the context of the present invention are disclosed in Kieliszek and Misiewicz (Folia Microbiol (Praha). 2014; 59(3): 241–250), WO 2015 / 191883 A1, WO 2008 / 102007 A1 and US 2010 / 0143970, the contents of which is fully incorporated herein by reference. In certain embodiments, a mutant variant of a microbial transglutaminase may be used for the conjugation of a linker to an antibody. That is, the microbial transglutaminasethat is used in the method of the present invention may be a variant of S. mobaraensistransgluatminase as set forth in SEQ ID NOs: 78 or 79. In certain embodiments, therecombinant S. morabaensis transglutaminase as set forth in SEQ ID NO:78maycomprise the mutation G254D. In certain embodiments, the recombinant S.morabaensis transglutaminase as set forth in SEQ ID NO:78 may comprise themutations G254D and E304D. In certain embodiments, the recombinant S.morabaensis transglutaminase as set forth in SEQ ID NO:78 may comprise themutations D8E and G254D. In certain embodiments, the recombinant S. morabaensistransglutaminase as set forth in SEQ ID NO:78 may comprise the mutations E124Aand G254D. In certain embodiments, the recombinant S. morabaensistransglutaminase as set forth in SEQ ID NO:78 may comprise the mutations A216Dand G254D. In certain embodiments, the recombinant S. morabaensistransglutaminase as set forth in SEQ ID NO:78 may comprise the mutations G254D and K331T. In a particular embodiment, the invention relates to the method according to the invention, wherein the transglutaminase is added to the conjugation reaction at a concentration of less than 200 U / mg antibody. Microbial transglutaminase may be added to the conjugation reaction at any concentration that allows efficient conjugation of an antibody with a linker. In certain embodiments, the concentration of microbial transglutaminase in a conjugation reaction may depend on the amount of antibody used in the same reaction. For example, a microbial transglutaminase may be added to the conjugation reaction at a concentration of less than 200 U / mg antibody, 150 U / mg antibody 100 U / mg antibody, 90 U / mg antibody, 80 U / mg antibody, 70 U / mg antibody, 60 U / mg antibody, 50 U / mg antibody, 40 U / mg antibody, 30 U / mg antibody, 20 U / mg antibody 10 U / mg antibody or 6 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 1 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 3 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 5 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 6 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 7.5 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 10 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 1-100 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 3-50 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 5-25 U / mg antibody. In certain embodiments a microbial transglutaminase may be added to the conjugation reaction at a concentration of 1-20 U / mg antibody, preferably at a concentration of 3- 15 U / mg antibody, more preferably at a concentration of 5-10 U / mg antibody. In certain embodiments, the transglutaminase for use in the method of the invention is a microbial transglutaminase. However, it is to be noted that an equivalent reaction may be carried out by an enzyme comprising transglutaminase activity that is of a non- microbial origin. Accordingly, also the antibody-payload conjugates according to the invention may be generated with an enzyme comprising transglutaminase activity that is of a non-microbial origin. In a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is added to the conjugation reaction at a concentration of 0.1 – 50 mg / mL. The antibody may be added to the conjugation reaction at any concentration that is suitable for obtaining efficient conjugation of the antibody. However, it is preferred that the antibody is added to the conjugation reaction at a concertation ranging from 0.1 - 50 mg / ml. That is, in a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is added to the conjugation reaction at a concentration of 0.1 – 50 mg / mL, e.g., 0.25 – 25 mg / mL, e.g., 0.5 – 12.5 mg / mL, e.g., 1 – 10 mg / mL, e.g., 2 – 7.5 mg / mL, e.g., about 5 mg / mL. Alternatively, the antibody may be added to the conjugation reaction at a concentration ranging from 1 - 20 mg / ml, from 2.5 – 20 mg / mL, from 5 – 20 mg / mL, or from 5 – 17 mg / mL. In a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is contacted with 2 – 100 molar equivalents of peptide linker. To obtain efficient conjugation, it is preferred that the linker is added to the antibody in molar excess. That is, in certain embodiments, the antibody is mixed with at least 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 molar equivalents of a linker. That is, in a particular embodiment, the invention relates to the method according to the invention, wherein the antibody is contacted with 2 – 100 molar equivalents of linker, e.g., 2 – 80 molar equivalents of linker, 2 – 70 molar equivalents of linker, 2 – 60 molar equivalents of linker, 2 – 50 molar equivalents of linker, 2 – 40 molar equivalents of linker, 2 – 30 molar equivalents of linker, 2 to 25 molar equivalents of linker, 2 - 20 molar equivalents of linker, 2 – 15 molar equivalents of linker, or 2 – 10 molar equivalents of linker. Alternatively, the antibody may be contacted with 2.5 – 100 molar equivalents of linker, e.g., 2.5 – 80 molar equivalents of linker, 2.5 – 70 molar equivalents of linker, 2.5 – 60 molar equivalents of linker, 2.5 – 50 molar equivalents of linker, 2.5 – 40 molar equivalents of linker, 2.5 – 30 molar equivalents of linker, 2.5 - 20 molar equivalents of linker, 2.5 – 15 molar equivalents of linker, 2.5 – 10 molar equivalents of linker, or 2.5 – 8 molar equivalents of linker. Alternatively, the antibody may be contacted with 5 – 100 molar equivalents of linker, e.g., 5 – 80 molar equivalents of linker, 5 – 70 molar equivalents of linker, 5 – 60 molar equivalents of linker, 5 – 50 molar equivalents of linker, 5 – 40 molar equivalents of linker, 5 – 30 molar equivalents of linker, 5 - 20 molar equivalents of linker, 5 – 15 molar equivalents of linker, or 5 – 10 molar equivalents of linker. In a particular embodiment, the invention relates to the method according to the invention, wherein the conjugation reaction is carried out in a buffered solution. The method according to the invention is preferably carried out at a pH ranging from 5 to 10. Thus, in one embodiment, the invention relates to a method according to the invention, wherein the conjugation of the linker to the antibody is achieved at a pH ranging from 5 to 10, from 6 to 9, from 6 to 8.5, even more preferably at a pH ranging from 6.5 to 8, or from 6.6 to 7.6. In certain embodiments, the invention relates to a method according to the invention, wherein the conjugation of the linker to the antibody is achieved at pH 6.6. In certain embodiments, the invention relates to a method according to the invention, wherein the conjugation of the linker to the antibody is achieved at pH 7.6. The method of the invention may be carried out in any buffer that is suitable for the conjugation of the payload to the linker. Buffers that are suitable for the method of the invention include, without limitation, Tris, MOPS, HEPES, PBS or BisTris buffer. The concentration of the buffer depends, amongst others, on the concentration of the antibody and / or the linker and may range from 10 – 1000 mM, 10 – 500 mM, 10 – 400 mM, 10 to 250 mM, 10 to 150 mM or 10 to 100 mM. Further, the buffer may comprise any salt concentration that is suitable for carrying out the method of the invention. For example, the buffer used in the method of the invention may have a salt concentration 250 mM, 200 mM, 150 mM, 140 mM, 130 mM, 120 mM, 110 mM, 100mM, 90 mM, 80 mM, 70 mM, 60 mM, 50 mM, 40 mM, 30 mM, 20 mMor 10 mM or no salts.That is, in a particular embodiment, the invention relates to the method according to the invention, wherein the buffered solution comprises a) a pH ranging from 5 to 10; and / or b) a buffer concentration ranging from 10 to 1000 mM; and / or c) a salt concentration below 250 mM. In one embodiment, the invention relates to the method according to the invention, wherein the buffered solution comprises a) a pH ranging from 6 to 9; and / or b) a buffer concentration ranging from 10 to 1000 mM; and / or c) a salt concentration below 250 mM. In another embodiment, the invention relates to the method according to the invention, wherein the buffered solution comprises a) a pH ranging from 6 to 8; and / or b) a buffer concentration ranging from 10 to 500 mM; and / or c) a salt concentration below 150 mM. In another embodiment, the invention relates to the method according to the invention, wherein the buffered solution comprises a) a pH ranging from 6 to 8; and / or b) a buffer concentration ranging from 10 to 200 mM; and / or c) a salt concentration below 50 mM. In one embodiment, the method of the invention is carried out in 50 mM Tris (pH 7.6), preferably without salts. In another embodiment, the method of the invention is carried out in 50 mM BisTris (pH 6.6), preferably without salts. In another embodiment, the method of the invention is carried out in 50 mM BisTris (pH 7.5), preferably without salts. It has to be noted that the optimal reaction conditions (e.g., pH, buffer, salt concentration) may vary between payloads and to some degree depend on the physicochemical properties of the linkers and / or payloads. However, no undue experimentation is required by the skilled person to identify reaction conditions that are suitable for carrying out the method of the invention. It is to be understood that the application encompasses any combination of the above- disclosed linker, antibody, MTG and / or buffer concentrations. In certain embodiments, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2- 80 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 1 – 20 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 0.1 – 20 mg / mL. In one embodiment, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2 - 50 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 1 – 15 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 1 – 20 mg / mL. In another embodiment, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2 - 30 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 2 – 15 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 2.5 – 20 mg / mL. In another embodiment, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2 - 20 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 5 – 15 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 2.5 – 20 mg / mL. In another embodiment, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2 - 15 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 5 – 15 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 5 – 20 mg / mL. In a particular embodiment, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2.5 – 12.5 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 5 – 15 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 5 – 20 mg / mL. In another embodiment, the invention relates to the methods according to the invention, wherein the antibody is contacted with 2 - 20 molar equivalents of the linker; and / or wherein the microbial transglutaminase is added to the conjugation reaction at a concentration ranging from 5 – 15 U / mg antibody and, optionally, wherein the antibody is added to the conjugation reaction at a concentration ranging from 2.5 – 20 mg / mL. It is to be noted that the specific reaction mixtures disclosed above may be freely combined with any of the buffer conditions disclosed herein. However, it is preferred that the specific components as defined above are mixed at a pH ranging from 6 to 8. In a particular embodiment, the invention relates to an antibody-payload conjugate which has been produced with the method according to the invention. That is, the invention further relates to an antibody-linker conjugate which has been generated with any of the aforementioned method steps. In the present invention, the subject is, in one embodiment, a mammal such as a dog, cat, pig, cow, sheep, horse, rodent, e.g., rat, mouse and guinea pig, or a primate, e.g., gorilla, chimpanzee and a human. In one embodiment, the subject is a human. Other aspects and advantages of the invention will be described in the following examples, which are given for purposes of illustration and not by way of limitation. Each publication, patent, patent application or other document cited in this application is hereby incorporated by reference in its entirety. List of embodiments:1. An antibody-drug conjugate (ADC) having the formula A-L, wherein A is anantibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, preferably a camptothecin cytotoxic molecule which is not cell-permeable; and as a third payload a toxin or a cytotoxin, more preferably, an auristatin, and even more preferably, an MMAE (Monomethyl auristatin E).2. The ADC according to embodiment 1, wherein the camptothecin is anexatecan.3. The ADC according to embodiment 1 or 2, wherein the second payload hasbeen modified to reduce its cell permeability.4. The ADC according to any one of embodiments 1 to 3, wherein the secondpayload has a glycine residue linked to said topoisomerase I inhibitor of the second payload.5. The ADC according to any one of embodiments 1 to 4, wherein the linker is apeptide linker.6. The ADC according to embodiment 5, wherein the first payload and / or secondpayload are linked to the N- or C-terminus of the peptide linker or to a side- chain of an amino acid residue comprised in the peptide linker; preferably wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker, or vice versa.7. The ADC according to any of embodiment 1 to 6, wherein the linker isconjugated to the antibody via an isopeptide bond formed between a glutamine residue comprised in the antibody and a primary amine comprised in the linker, preferably wherein the primary amine is comprised in a lysine residue, a lysine mimetic or a lysine derivative comprised in a peptide linker or wherein the primary amine is comprised in an amino acid residue having the structure NH2- (CH2)1-10-COOH comprised in a peptide linker.8. The ADC according to any one of embodiments 1 to 7, wherein the linkerfurther comprises at least one positively charged amino acid residue, preferably wherein the at least one positively charged amino acid residue is selected from arginine and / or histidine.9. The ADC according to any one of embodiments 1 to 8, wherein the linkercomprises the following structure: [payload1]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 2]; or [payload2]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2; and X is either absent or a self-immolative group, preferably PABC.10. The ADC according to embodiment 9, wherein (Aa)m + (Aa)n + (Aa)o is > 0,preferably wherein (Aa)n+ (Aa)ois > 0.11. The ADC according to embodiment 9 or 10, wherein Z2 is a dicarboxylic acidlinking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and wherein one payload is directly or indirectly linked to the C-terminal end of (Aa)mand the other payload is directly or indirectly linked to the C-terminal end of (Lys) or (Aa)o, or vice versa.12. The ADC according to any one of embodiments 9 to 11, wherein the linkercomprises the following structure: [payload1]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 2]; or [payload2]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m is an integer ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.13. The ADC according to any one of embodiments 9 to 12, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).14. The ADC according to any one of embodiments 9 to 13, wherein (Aa)n-(Lys)-(Aa)o is or comprises the sequence motif RK or RKAA (in N -> C direction).15. The ADC according to any one of embodiments 1 to 14, wherein said ADCcomprises more than one first payloads and / or more than one second payloads.16. The ADC according to any one of embodiments 1 to 15, wherein the linker isa peptide linker and wherein the third payload is linked to the N- or C-terminus of the peptide linker or wherein the third payload is linked to a side chain of an amino acid residue comprised in the peptide linker.17. The ADC according to embodiment 16, wherein two payloads are linked to thesame functional group of the peptide linker, preferably via a chemical linker comprising a disubstituted amine.18. The ADC according to embodiment 17, wherein the linker consists of orcomprises the structure: ( X- [payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X- ( 1-6- C(=O)-(Aa)p / p*-Z3-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2, even more preferably wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, preferably PABC.19. The ADC according to embodiment 18, wherein (Aa)n + (Aa)o is > 0.20. The ADC according to any one of embodiments 17 to 19, wherein the linkerconsists of or comprises the structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- X-[payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)- (Aa)p / p*-X-[payload])2;or ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- N-((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.21. The ADC according to any one of embodiments 18 to 20, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).22. The ADC according to any one of embodiments 18 to 21, wherein (Aa)n-(Lys)-(Aa)o is or comprises the sequence motif RK or RKAA (in N -> C direction).23. The ADC according to any one of embodiments 1 to 22, wherein the linkercomprises or consists of the following structure: 24. The ADC according to any one of embodiments 1 to 23, wherein the antibodyis an IgG antibody, preferably an IgG1 or IgG4 antibody.25. The ADC according to any one of embodiments 7 to 24, wherein the glutamineresidue is residue Q295 (EU numbering) of the CH2 domain of an IgG antibody.26. The ADC according to any one of embodiments 1 to 25, wherein the antibodyis a glycosylated antibody, preferably wherein the antibody is an IgG antibody glycosylated at residue N297 (EU numbering).27. The ADC according to any one of embodiments 1 to 26,wherein the antibody is selected from the group consisting of: Trastuzumab, Brentuximab, , Gemtuzumab, Inotuzumab, Avelumab, Cetuximab, Rituximab, Daratumumab, Pertuzumab, Vedolizumab, Ocrelizumab, Tocilizumab, Ustekinumab, Golimumab, Obinutuzumab, Sacituzumab, Belantamab, Polatuzumab, Enfortumab, Endrecolomab, Gemtuzumab,Loncastuximab, Mecbotamab, Adecatumumab, D93, Gatipotuzumab, Labetuzumab, Tusamitamab, Upifitamab, Lifastuzumab, Mirvetuximab, Sofituzumab, Anetumab, Tisotumab, Cofituzumab, Praluzatamab, Ladriatuzumab, Belantamab, Patritumab, Cetuximab, Nimotuzumab, Matuzumab, Portuzumab, Citatuzumab, Tucotuzumab, Endrecolomab and Indatuximab; and / or wherein the antibody specifically binds to an antigen selected from the group consisting of: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38, HER2, Integrin 4 7, CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA,CD79b, Nectin-4, EpCAM, CD33, CD19, AXL, dn-collagen, TA-MUC1, carcinoembryonic cell adhesion molecule 5, CEACAM5, NaPi2b, FR ,MUC16, mesothelin, TF, CD166, LIV-1, ERBB3, EGFR, TACSTD1, Claudin 18.2, CLDN1, CLDN6, CLDN9, EphA2, B7H4, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, Cadherin17, ST14, P-cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG-72, FGFRs (e.g., FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 (CD318), GPCR5A, GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4.28. A pharmaceutical composition comprising the ADC according to any one ofembodiments 1 to 27 and at least one pharmaceutically acceptable ingredient.29. The ADC according to any one of embodiments 1 to 27 or the pharmaceuticalcomposition of embodiment 28 for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease, in particular wherein the neoplastic disease is cancer.30. The ADC according to any one of embodiments 1 to 27 and 29 or thepharmaceutical composition of embodiment 28 or 29, wherein the antibody-payload conjugate comprises Trastuzumab and wherein the neoplastic disease is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; wherein the antibody-payload conjugate comprises Polatuzumab and wherein the neoplastic disease is a B-cell associated cancer; preferably, wherein the B-cell associated cancer is non-Hodgkin lymphoma, in particular wherein the B-cell associated cancer is diffuse large B-cell lymphoma; or wherein the antibody-payload conjugate comprises Enfortumab or an Enfortumab variant and wherein the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer.31. The ADC according to any one of embodiments 1 to 27 and 29 or thepharmaceutical composition of embodiment 28 or 29, wherein the antibody-payload conjugate comprises an antibody targeting NaPi2b, preferably wherein the antibody targeting NaPi2b is Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99, or with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101, and wherein the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer.32. The ADC according to any one of embodiments 1 to 27 and 29 or thepharmaceutical composition of embodiment 28 or 29, wherein the antibody-payload conjugate comprises an antibody targeting Nectin-4, preferably wherein the antibody targeting Nectin-4 is m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97, or Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77, and wherein the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer, preferably wherein the ADC comprises a linker having the structure: A linker comprising a first, a second, and a third payload, wherein the firstpayload is a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; wherein the second payload is a topoisomerase I inhibitor which is not cell- permeable, preferably a camptothecin cytotoxic molecule which is not cell- permeable; and wherein the third payload is a toxin or a cytotoxin, more preferably an auristatin, and even more preferably MMAE (Monomethyl auristatin E); preferably wherein the linker is for conjugation to an antibodyThe linker according to embodiment 33, wherein the camptothecin is exatecanor DXd.The linker according to embodiment 33 or 34, wherein the second payload hasbeen modified to reduce its cell permeability.The linker according to any one of embodiments 33 to 35, wherein the secondpayload has a glycine residue linked to said topoisomerase I inhibitor of the second payload.The linker according to any one of embodiments 33 to 36, wherein the linkeris a peptide linker.The linker according to embodiment 37, wherein the first payload and / orsecond payload are linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker; preferably wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker, or vice versa.The linker according to any of embodiment 33 to 38, wherein the linkercomprises a primary amine for conjugation to an antibody, preferably wherein the primary amine is comprised in a lysine residue, a lysine mimetic or a lysine derivative; or wherein the primary amine is comprised in an amino acid residue having the structure NH2-(CH2)1-10-COOH; preferably wherein the amino acid residues are comprised in a peptide linker.The linker according to any one of embodiments 33 to 39, wherein the linkerfurther comprises at least one positively charged amino acid residue, preferably wherein the at least one positively charged amino acid residue is selected from arginine and / or histidine.41. The linker according to any one of embodiments 33 to 40, wherein the linkercomprises the following structure: [payload1]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 2]; or [payload2]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2; and X is either absent or a self-immolative group, preferably PABC.42. The linker according to embodiment 41, wherein (Aa)m + (Aa)n + (Aa)o is > 0,preferably wherein (Aa)n+ (Aa)ois > 0.43. The linker according to embodiment 41 or 42, wherein Z2 is a dicarboxylic acidlinking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and wherein one payload is directly or indirectly linked to the C-terminal end of (Aa)mand the other payload is directly or indirectly linked to the C-terminal end of (Lys) or (Aa)o, or vice versa.44. The linker according to any one of embodiments 41 to 43, wherein the linkercomprises the following structure: [payload1]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 2]; or [payload2]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m is an integer ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.45. The linker according to any one of embodiments 41 to 44, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).46. The linker according to any one of embodiments 41 to 45, wherein (Aa)n-(Lys)-(Aa)o is or comprises RK or RKAA (in N -> C direction).47. The linker according to any one of embodiments 33 to 46, wherein the linkeris a peptide linker and wherein the third payload is linked to the N- or C- terminus of the peptide linker or wherein the third payload is linked to a side chain of an amino acid residue comprised in the peptide linker.48. The linker according to embodiment 47, wherein two payloads are linked tothe same functional group of the peptide linker, preferably via a chemical linker comprising a disubstituted amine.49. The linker according to embodiment 48, wherein the linker consists of orcomprises the structure: ( X- [payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X- ( 1-6- C(=O)-(Aa)p / p*-Z3-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2, even more preferably wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, preferably PABC.50. The linker according to embodiment 49, wherein (Aa)n + (Aa)o is > 0.51. The linker according to any one of embodiments 48 to 50, wherein the linkerconsists of or comprises the structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- X-[payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)- (Aa)p / p*-X-[payload])2;or ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- N-((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.52. The linker according to any one of embodiments 49 to 51, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).53. The linker according to any one of embodiments 49 to 52, wherein (Aa)n-(Lys)-(Aa)o is or comprises RK or RKAA (in N -> C direction).54. The linker according to any one of embodiments 47 to 53, wherein the linkercomprises or consists of the following structure:

[0004] 55. A method for the preparation of an antibody-drug conjugate comprising a stepof conjugating a peptide linker according to any of embodiments 33 to 54 to an antibody.56. A method for the conjugation of a peptide linker according to any one ofembodiments 37 to 54 to an antibody using a transglutaminase (TG), the method comprising a) mixing the antibody, the peptide linker and a transglutaminase (TG) within a fluid, thereby conjugating the linker-payload to the antibody in one step under the catalyzing effect of the TG, and b) extracting the conjugate obtained in step a) from the fluid.57. The method according to embodiment 56, wherein the peptide linker isconjugated to a glutamine residue comprised in the antibody via a primary amine comprised in an amino acid residue of the peptide linker.58. The method according to embodiment 56 or 57, wherein the peptide linker isconjugated to a glutamine residue comprised in an Fc domain of an IgG antibody.59. The method according to embodiment 57 or 58, wherein the glutamine residueto which the peptide linker is conjugated is glutamine residue Q295 (EU numbering) of the CH2 domain of an IgG antibody.60. The method according to any one of embodiments 56 to 59, wherein theantibody is a glycosylated IgG antibody.61. The method according to embodiment 60, wherein the IgG antibody isglycosylated at residue N297 (EU numbering) of the CH2 domain.The method according to any one of embodiments 56 to 61, wherein theantibody is selected from the group consisting of: m290, Trastuzumab, Brentuximab, , Gemtuzumab, Inotuzumab, Avelumab, Cetuximab, Rituximab, Daratumumab, Pertuzumab, Vedolizumab, Ocrelizumab, Tocilizumab, Ustekinumab, Golimumab, Obinutuzumab, Sacituzumab, Belantamab, Polatuzumab, Enfortumab, Endrecolomab, Gemtuzumab,Loncastuximab, Mecbotamab, Adecatumumab, D93, Gatipotuzumab, Labetuzumab, Tusamitamab, Upifitamab, Lifastuzumab, Mirvetuximab, Sofituzumab, Anetumab, Tisotumab, Cofituzumab, Praluzatamab, Ladriatuzumab, Belantamab, Patritumab, Cetuximab, Nimotuzumab, Matuzumab, Portuzumab, Citatuzumab, Tucotuzumab, Endrecolomab, and Indatuximab; and / or wherein the antibody specifically binds to an antigen selected from the group consisting of: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38,HER2, Integrin 4 7, CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA,CD79b, Nectin-4, EpCAM, CD33, CD19, AXL, dn-collagen, TA-MUC1,carcinoembryonic cell adhesion molecule 5, CEACAM5, NaPi2b, FR ,MUC16, mesothelin, TF, CD166, LIV-1, ERBB3, EGFR, TACSTD1, Claudin 18.2, CLDN1, CLDN6, CLDN9, EphA2, B7H4, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, Cadherin17, ST14, P-cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG-72, FGFRs (e.g., FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 (CD318), GPCR5A, GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4.The method according to any one of embodiments 56 to 62, wherein thepeptide linker is suitable for conjugation to a glycosylated antibody with a conjugation efficiency of at least 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90% or 95%.The method according to any one of embodiments 56 to 63, wherein thetransglutaminase is a microbial transglutaminase (MTG), preferably whereinthe microbial transglutaminase is derived from a Streptomyces species, inparticular Streptomyces mobaraensis.A method of treating cancer in a subject in need, comprising administering tothe subject (an effective amount of) an ADC according to any one of claims 1 to 27 or a pharmaceutical composition according to claim 28.The method of embodiment 65, wherein:the ADC comprises Trastuzumab and the cancer is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; or the ADC comprises Polatuzumab and the neoplastic disease is a B-cell associated cancer, preferably non-Hodgkin lymphoma, in particular diffuse large B-cell lymphoma; or the ADC comprises Enfortumab or an Enfortumab variant and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer. The method of embodiment 65, wherein the ADC comprises an antibodytargeting NaPi2b, preferably Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99, or with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101, and the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer. The method of embodiment 65, wherein the ADC comprises an antibodytargeting Nectin-4, preferably m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97, or Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77, and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer, preferably wherein the ADC comprises a linker having the structure: Use of an ADC according to any one of embodiments 1 to 27 or apharmaceutical composition according to embodiment 28 in the manufacture of a medicament for the treatment of cancer in a subject in need. The use according to embodiment 69, wherein: the ADC comprises Trastuzumab and the cancer is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; or the ADC comprises Polatuzumab and the neoplastic disease is a B-cell associated cancer, preferably non-Hodgkin lymphoma, in particular diffuse large B-cell lymphoma; or the ADC comprises Enfortumab or an Enfortumab variant and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer. The use according to embodiment 69, wherein the ADC comprises an antibody targeting NaPi2b, preferably Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99, or with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101, and the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer. The use according to embodiment 69, wherein the ADC comprises an antibody targeting Nectin-4, preferably m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97, or Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77, and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer, preferably wherein the ADC comprises a linker having An antibody-drug conjugate (ADC) having the formula A-L, wherein A is anantibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a camptothecin cytotoxic molecule which is not cell- permeable; wherein the cytotoxic molecule of the first and second payload is an exatecan; wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload; and as a third payload an auristatin, preferably an MMAE; wherein said ADC consists of two first payloads, two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”); and wherein said antibody is an IgG, preferably, an IgG1 antibody. The ADC according to embodiment 65, wherein the antibody is m290.An antibody-drug conjugate comprising:a) an antibody targeting Nectin-4, preferably m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97; and ; wherein the linker is conjugated to the antibody via an isopeptide bond formed between glutamine residue Q295 (EU numbering) of the CH2 domain of the antibody and a primary amine comprised in the lysine residue comprised in the RK sequence motif of the linker. An antibody-drug conjugate comprising:a) an antibody targeting Nectin-4, preferably Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77; and b) a linker having the structure:

[0005] ; wherein the linker is conjugated to the antibody via an isopeptide bond formed between glutamine residue Q295 (EU numbering) of the CH2 domain of the antibody and a primary amine comprised in the lysine residue comprised in the RK sequence motif of the linker.77. A pharmaceutical composition for treating cancer comprising the ADCaccording to embodiment 75 or 76. BRIEF DESCRIPTION OF THE DRAWINGSFigure 1A: Cytotoxic activity of T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa on HER2-overexpressing SK-BR3 breast cancer cells.Figure 1B: Cytotoxic activity of T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa onHER2-overexpressing SK-BR3 breast cancer cells.Figure 2: Cell counts of viable cells after incubation of the indicated ADCs.Figure 3A: T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa shows superior and long-lasting anti-tumor activity in vivo compared to anti-HER2-ADC DS-8201a.Figure 3B: The ADC of the present invention T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa confirms highly efficient anti-tumor efficacy and shows superior and long-lasting anti-tumor activity in vivo compared to anti-HER2-ADCDS-8201a.Figure 4: Linker structure: Exa-PABC-AA-C2-RKAA-PABC-G-Exa (A) and Exa-PABC-ARA-C2-RKAA-PABC-G-Exa (B).Figure 5: Schematic depiction of a DAR4 (2+2) ADC of this invention with twodifferent Exatecan.Figure 6: Schematic depiction of T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa.Figure 7: Schematic depiction of T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa.Figure 8: Linker structure with three payloads: (Exa-PABC-GR / Exa-G-PABC-GR)-CEA-C2-RK-PABC-MMAE. Figure 9: Anti-tumoral effects of ARC-121 vs FDA approved ADC Padcev® in SUM190PT tumor model Figure 10: Anti-tumoral effects of ARC-121 and FDA approved ADCs Trodelvy® and Padcev® in MAXFTN_574 tumor modelFigure 11: Anti-tumoral effects of ARC-121 vs FDA approved ADC Padcev® and acombination of monopayload ADCs in SUM190PT tumor modelFigure 12: Anti-tumoral effects of ARC-401 vs FDA approved ADC Padcev® inSUM190PT tumor modelFigure 13: Anti-tumoral effects of ARC-401 and FDA approved ADCs Trodelvy® andPadcev® in MAXFTN_574 tumor model Figure 14: Linker structure: RKAA-PABC-MMAE Figure 15: Cell counts of viable cells after incubation of the indicated ADCs. Figure 16: Anti-tumoral effects of ARC-401 and FDA-approved ADC Padcev® in BLCU003 tumor model It is to be understood that the methods described in this disclosure are not limited to particular methods and experimental conditions disclosed herein; as such methods and conditions may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Furthermore, the experiments described herein, unless otherwise indicated, use conventional molecular and cellular biological and immunological techniques within the skill of the art. Such techniques are well known to the skilled worker, and are explained fully in the literature. See, e.g., Ausubel, et al., ed., Current Protocols in Molecular Biology, John Wiley & Sons, Inc., NY, N.Y. (1987-2008), including all supplements, Molecular Cloning: A Laboratory Manual (Fourth Edition) by MR Green and J. Sambrook and Harlow et al., Antibodies: A Laboratory Manual, Chapter 14, Cold Spring Harbor Laboratory, Cold Spring Harbor (2013, Unless otherwise defined herein, scientific and technical terms used herein have the meanings that are commonly understood by those of ordinary skill in the art. In the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The use of “or” means “and / or” unless stated otherwise. The use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. As used herein, unless otherwise stated, the singular forms “a,” “an,” and “the” include plural reference. Thus, for example, a reference to “a protein” includes a plurality of protein molecules. Generally, nomenclatures used in connection with cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. The methods and techniques provided herein are generally performed according to conventional methods well-known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. Enzymatic reactions and purification techniques are performed according to manufacturer’s specifications, as commonly accomplished in the art or as described herein. The nomenclatures used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Standard techniques are used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery and treatment of patients. EXAMPLESGENERAL MATERIAL AND METHODS FOR THE PRODUCTION OF ADCEnhertu® (DS-8201a or “fam-trastuzumab deruxtecan-nxki”) and Herceptin® (trastuzumab) were bought at the pharmacy. Linker-payloads Exa-PABC-AA-C2-RKAA-PABC-G-Exa and Exa-PABC-ARA-C2-RKAA-PABC-G-Exa (see Figure 4 for chemical structure) were customsynthesized by WuXi. As it can be seen in Figure 4, they both contain anexatecan (“Exa”) and a glycine-exatecan (“Gly-Exa”) topoisomerase I inhibitor. ADCs of the invention “T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa” and “T-Exa- PABC-ARA-C2-RKAA-PABC-G-Exa”: In order to generate the ADCs of the invention “T-Exa-PABC-AA-C2-RKAA- PABC-G-Exa” (Figure 6) and “T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa” (Figure 7), an enzymatic method using linkers with a lysine residue as described by Spycher et al. (WO 2019 / 057772 and WO 2020 / 188061) was used. Briefly, conjugation reactions were performed by mixing 5 mg / ml of native, glycosylated monoclonal antibody trastuzumab (rebuffered in reaction buffer, see below), microbial transglutaminase (MTG, Zedira) at a concentration of 5- 10 U / mg, and 5-20 molar equivalents of the indicated linker-payload, in BisTris pH 6.0-6.8 for 24 hours at 37°C in a rotating thermomixer. In this way, linker- payloads of the invention were conjugated to glutamine 295 of each antibody (see Figure 5) resulting in a DAR4 (2+2). Conjugation efficiency was assessed by LC-MS, under TCEP reduced conditions (calculations see below). Reduction of samples was achieved by incubation of the samples for 15 min at 37°C in 50 mM TCEP (final) and 50 mM Tris buffer. Calculation of conjugation efficiency by LCMS: after reduction, samples were analyzed on a Compact QTOF spectrometer (Bruker) coupled to an 1260 Infinity II LC (Agilent) equipped with an ACQUITY Premier Protein BEH C4 Column. Conjugation efficiency (CE) was calculated from deconvoluted spectra and presented in %. Intensities resulting from both glycoforms (G1F and G0F) were taken into account for the calculation, according to the formula: With cj = conjugated and ncj = non-conjugated The conjugation efficiency for the ADCs “T-Exa-PABC-AA-C2-RKAA-PABC- G-Exa” and “T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa” was at least 95 %.2. EXAMPLE 1: ANTIBODY-DRUG CONJUGATES USING TWO DIFFERENTTYPES OF TOPOISOMERASE I INHIBITORS SHOW POTENT ANTI- TUMOR EFFECTS IN VITROIn order to assess whether the ADCs of the invention are able to kill HER2 positive tumor cells, an in vitro cytotoxicity assay was performed.Method For a cell cytotoxicity assay, SK-BR-3 breast cancer cells (ATCC, HTB-30) were seeded at 2000 cells per well in a 96-well cell culture plate and grown at 37°C in a humidified chamber at 5% CO2. After 24h, cells were incubated with serially diluted Trastuzumab (T), T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa and T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa. Cell viability was measured using Cell Titre Glo (Promega) after 5 days of treatment. Percent viability was calculated as the luminescence values of treated cells divided by the values of untreated control cells. The EC50 was derived from the survival curve using the sigmoidal nonlinear regression analysis in GraphPad Prism. Results Figure 1A and 1B show that the ADCs of the invention T-Exa-PABC-AA-C2- RKAA-PABC-G-Exa and T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa (both DAR4) exert a very high cytotoxic activity with an IC50 of about 0.07 nM and 0.09 nM, respectively against HER-2 over-expressing SK-BR-3 breast cancer cells in vitro. Trastuzumab as control shows only limited cytotoxicity on this cellline.EXAMPLE 2: BYSTANDER KILLING EFFECTSMethod: In order to assess the bystander activity of our topoisomerase I inhibitors exatecan (“Exa”) and glycine-exatecan (“Gly-Exa”), a control ADC was generated with trastuzumab having just Gly-Exa as payload (T-RKAA-PABC- G-Exa) using the same method as described above, resulting in a drug-to- antibody ratio of 2 (DAR2). For the bystander assay, HER-2-positive SK-BR-3 (ATCC HTB-30) breast cancer cells and HER-2-negative MDA-MB-468 (DSMZ ACC 738) cells were seeded into 6-well plates at a ratio of 1:5.5 and grown at 37°C in a humidified chamber at 5% CO2. After 24h, cells were treated with payload-adjusted concentrations of ADCs: 0.2 nM Enhertu® (bought at pharmacy), 0.4 nM T- Exa-PABC-AA-C2-RKAA-PABC-G-Exa and 0.8 nM T-RKAA-PABC-G-Exa, concentrations that are non-toxic to target-negative cells and toxic to target- positive cells. After 5 days, cells were harvested, stained with PE-HER2 (Biolegend, cat nr.324405), fixed with Cyto-Fast fixing solution (Biolegend, cat nr.426803) and measured in duplicates on the CytoFlex cytometer. Single cell counts for target-positive and target-negative populations were extracted per well with Flow Jo and plotted in GraphPad Prism. Results: In order to assess the bystander activity of our topoisomerase I inhibitors “Exa” and “Gly-Exa” a coculture cell killing assay was performed. DS8201a showed cell killing to both HER2 positive and HER2 negative cells, confirming the bystander activity of the payload of DS8201a, as described in the literature. Interestingly, our control ADC having just a “Gly-Exa” as payload (T-RKAA- PABC-G-Exa) was able to only kill HER2 positive cells but not co-culture HER2-negative cells, clearly showing that Gly-Exa is not able to exert bystander activity. The ADC of the invention T-Exa-PABC-AA-C2-RKAA- PABC-G-Exa, having Gly-Exa and Exa as payload, showed very potent bystander activity that was driven by the Exa payload only, because Gly-Exa is not able to exert bystander activity. In summary, the ADCs of the invention have two types of topoisomerase I inhibitors, Exa (bystander activity) and Gly- Exa (no bystander activity).EXAMPLE 3: ANTIBODY-DRUG CONJUGATES OF THE INVENTIONSHOW SUPERIOR ANTI-TUMOR EFFECTS IN VIVO THAN DS-8201AThe anti-HER2 ADCs T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa (Figure 6), and T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa (Figure 7) were investigated in vivo for tumor growth inhibition and were compared to the commercially available DS-8201a. Trastuzumab (Herceptin®) and DS-8201a (Enhertu®) were purchased, all other ADCs were produced in-house as described above. Method 1 x 107HER2-positive JIMT-1 human breast carcinoma cells were implanted s.c. with 50% matrigel into CB-17 SCID mice at Charles River Discovery Research Services North Carolina, US. Tumor dimensions and body weights were recorded as per study protocol. The tumor volume was calculated according to the formula volume = (width)2x length x 0.5. When the average tumor size reached about 100-150 mm3, mice were allocated using a non- random stratification protocol into the treatment groups comprising five mice each. ADCs according to this invention, T-Exa-PABC-AA-C2-RKAA-PABC-G- Exa, and T-Exa-PABC-ARA-C2-RKAA-PABC-G-Exa at doses of 10 mg / kg, DS-8201a at 5 mg / kg (same payload dose as the ADCs of the invention) and Trastuzumab at 20 mg / kg by intravenous tail-vein injection on days 1 (day of randomization) and 8. Mice in the control group were injected with 25 mM Histidine. Results Figure 3A and 3B show the in vivo anti-tumor efficacy of the anti-HER2 ADC of this invention, T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa (DAR4) and T-Exa- PABC-ARA-C2-RKAA-PABC-G-Exa (DAR4) as compared with DS-8201a (Enhertu®, DAR 8) in a HER2-overexpressing JIMT-1 tumor model. Specifically, the animals received two doses of 10 mg / kg of the corresponding ADC of the invention or 5 mg / kg of DS-8201s (animals received equal payload dose, because of the DAR difference). Very surprisingly, T-Exa-PABC-AA-C2-RKAA-PABC-G-Exa and T-Exa-PABC- ARA-C2-RKAA-PABC-G-Exa demonstrated strong anti-tumoral activity. In contrast, at an equal payload dose, DS-8201a showed only transient anti- tumoral activity until about day 18, followed by rapid re-growth of the tumors. The trastuzumab control group (20 mg / kg) demonstrated only slight tumor growth retardation.EXAMPLE 4: ANTIBODY-DRUG CONJUGATES COMPRISING TWODIFFERENT TYPES OF TOPOISOMERASE I INHIBITORS AND ANOTHER PAYLOAD WITH A DIFFERENT MECHANISM OF ACTION To demonstrate that the invention may also include antibody-drug conjugates comprising two different types of topoisomerase I inhibitors (Exa, Gly-Exa) and another payload with a different mechanism of action (MMAE), a linker- payload comprising three different drug types (Exa, Gly-Exa, and MMAE) was designed and conjugated to multiple different monoclonal antibodies resulting in DAR6 (2+2+2) ADCs comprising 2 Exa, 2 Gly-Exa, and 2 MMAE. Method Multiple native, glycosylated monoclonal antibodies (ARA-27, ARA-01, ARA- 29, m290) were conjugated to a linker-payload comprising two different types of topoisomerase I inhibitors and another payload with a different mechanism of action ((Exa-PABC-GR / Exa-G-PABC-GR)-CEA-C2-RK-PABC-MMAE) as follows: conjugation reactions were performed by mixing 5-10 mg / mL of native, glycosylated monoclonal antibodies ARA-27, ARA-01, ARA-29, m290, microbial transglutaminase at a concentration of 4-8 U / mg, and 4-5 molar equivalents of the indicated linker-payload, in 10-50 mM BisTris pH 6.0-6.8 for 6-24 hours at 37°C in a rotating thermomixer. Conjugation efficiency was determined by LCMS, as described in the section general material and methods for the production of ADC. The chemical structure of the linker with three payloads (Exa, Gly-Exa and MMAE) is depicted in Figure 8. Results Linker-payload comprising two different types of topoisomerase I inhibitors and another payload with a different mechanism of action ((Exa-PABC-GR / Exa-G- PABC-GR)-CEA-C2-RK-PABC-MMAE) led to very high conjugation efficiencies (Table 1) on multiple native, fully glycosylated antibodies, resulting in DAR6 (2+2+2) ADCs comprising 2 Exa, 2 Gly-Exa and 2 MMAE. Table 1. Conjugation efficiency (%) using Exa / Gly-Exa / MMAE linker- payload to generate DAR6 (2+2+2) ADCs comprising 2 Exa, 2 Gly-Exa, and 2 MMAE based on different monoclonal antibodiesTarget Conjugation efficiencyMonoclonal antibody (%) ARA-01 (SEQ ID: 71, SEQ ID: CD79b 95% 72) ARA-27 (SEQ ID: 94, SEQ ID: Nectin-4 5 96% 95) ARA-29 (SEQ ID: 100, SEQ ID: NaPi2b 99% 101) m290 (SEQ ID: 96, SEQ ID: Nectin-4 99% 97)EXAMPLE 5: ANTI-NECTIN-4 ANTIBODY BASED ADC IN VIVO TUMORGROWTH INHIBITION An anti-Nectin-4 antibody (in this example ARA-27, SEQ ID NO.94 and 95) was conjugated with the peptide linker shown in Figure 8 and the resultingADC (ARC-121) was investigated in vivo for tumor growth inhibition in aSUM190PT (Nectin-4 positive, solid tumor) xenograft model and compared to the FDA approved ADC Padcev® (enfortumab-vedotin). Method For SUM190PT xenografts, 2 x 106cells were injected into the mammary fatpad of CB17 SCID mice (Janvier). Tumor dimensions and body weights were recorded three times weekly. The tumor volume was calculated according to the formula volume = (width)2x length x 0.5. When the average tumor size reached about 170mm3, mice were allocated using a non-random stratification protocol to the respective treatment groups, N=5. ADCs were intravenously injected once on the day of randomization (d=0). The conjugation of anti-Nectin-4 antibody (ARA-27) with peptide linker as shown in Figure 8 was performed as described in general method section 1. Padcev® was bought at the Pharmacy. 0.5mg / kg of ADC of the invention (ARC-121) and 0.5mg / kg of Padcev® was injected intravenously on day 0. Mice in the vehicle control group were injected with formulation buffer. All mouse experiments were performed in accordance with Swiss guidelines and were approved by the Veterinarian Office of Zürich, Switzerland. Results The ADC of the invention showed a significant anti-tumor effect at a dose of only 0.5mg / kg, whereas Padcev® was hardly active at this dose (Figure 9).7. EXAMPLE 6: ANTI-NECTIN-4 ANTIBODY BASED ADC IN VIVO TUMORGROWTH INHIBITION An anti-Nectin-4 antibody (in this example ARA-27, SEQ ID NO.94 and 95) was conjugated with the peptide linker shown in Figure 8 and the resulting ADC (ARC-121) was investigated in vivo for tumor growth inhibition in theMAXFTN_574 (Nectin-4 positive, triple negative breast cancer TNBC) patient- derived xenograft (PDX) model and compared to the FDA approved ADCs Trodelvy® (approved for the treatment of TNBC) and anti-Nectin-4 ADC Padcev®. Method Female NMRI nu / nu mice (Charles River) were unilaterally implanted subcutaneously with MAXFTN_574 tumor tissue passaged from donor- animals. Once tumors reached a volume of approx. 100 mm³. Mice were randomized into the different treatment arms of 5 animals each. Tumor volume and body weight were measured bi-weekly.2.5 mg / kg of ADC of this invention 2.5 mg / kg of Trodelvy® or 2.5 mg / kg of Padcev® were injected intravenously on day 0 and day 7. Mice in the control group were injected with formulation buffer. ADC was produced as described in general method section 1. Trodelvy® and Padcev® were provided by Charles River, studies were performed at Charles River Laboratories Germany GmbH, Freiburg. Results The ADC of this invention ARC-121 showed a better anti-tumoral effect than FDA approved ADCs (Figure 10).8. GENERAL MATERIAL AND METHODS FOR THE PRODUCTION OF ADCSAll the linker-payloads (Exa-PABC-GR / Exa-G-PABC-GR)-CEA-C2-RK-PABC- MMAE (Figure 8), Exa-PABC-AA-C2-RKAA-PABC-G-Exa (Figure 4A), and RKAA-PABC-MMAE (Figure 14), were custom synthesized by WuXi AppTec or Levena. DNA constructs encoding ARA-04 (anti-Nectin 4) with heavy and light chain consisting of the sequences of SEQ ID NOs: 75 and 95, and ARA- 27 (anti-Nectin-4) with heavy and light chain consisting of the sequences of SEQ ID NOs: 94 and 95 were transiently transfected into suspension-adapted CHO-K1 cells and expressed in serum-free / animal component-free media by Evitria or Biointron, respectively. The proteins were purified from the supernatants by Protein A affinity chromatography (Mab Select Sure column; GE Healthcare). m290 with heavy and light chain consisting of the sequences of SEQ ID NOs: 96 and 97 was purified from a monoclonal CHO-K1 cell by Wuxi. Briefly, conjugation reactions were performed by mixing 5-10 mg / mL of native, glycosylated monoclonal antibody rebuffered in 50 mM BisTris pH 6.6 or 50 mM Tris pH 7.6, microbial transglutaminase (MTG, in-house purified, or from Zedira, T240) at a concentration of 3-8 U / mg, and 3-5 molar equivalents of linker-payload, in 50 mM BisTris pH 6.6 or 50 mM Tris pH 7.6 for 6-24 hours at 37°C in a rotating thermomixer. In this way, linker-payloads were conjugated to glutamine 295 of each antibody resulting in a DAR2, DAR4 (2+2) or DAR6 (4+2). ADCs were subsequently purified with Protein A resin or Hydrophobic Interaction Chromatography (HIC).9. SYNTHESIS OF LINKER WITH THREE PAYLOADS (EXA-PABC-GR / EXA-G-PABC-GR)-CEA-C2-RK-PABC-MMAE (FIGURE 8) To a solution of compound 1 (50.0 g, 168 mmol, 1.0 eq.) in DCM (500 mL) wasadded (4-aminophenyl) methanol (31.1 g, 252 mmol, 1.5 eq.), and EEDQ (62.4 g, 252 mmol, 1.5 eq.). The mixture was stirred at 25 °C for 1 hr. The reaction was monitored by LCMS 1 (MD00822-2-P1A2, Rt = 0.50 min, MS cal.: 402.4, MS observed: [M+H]+ 403.2) and showed compound 1 was consumed andcompound 2 was detected. The reaction mixture was concentrated underreduced pressure to give a residue. The residue was triturated with MTBE for 20 min, then filtered and concentrated under reduced pressure to give a residue. The crude product compound 2 (82.0 g, crude) was used into the nextstep without further purification.Gen for preparationTo a solution of compound 2 (70.0 g, 174 mmol, 1.0 eq.) in THF (640 mL) wasadded N-ethylethanamine (114 g, 1.55 mol, 160 mL, 8.93 eq.). The mixture was stirred at 25 °C for 1 hr. The reaction was monitored by LCMS 1 (MD00822-17-P1A2, Rt = 0.07 min, MS cal.: 180.2, MS observed: [M+H]+181.1) and showed compound 2 was consumed and compound 3 wasdetected. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was triturated with isopropyl ether (2000.0 mL *1), then filtered and concentrated under reduced pressure to give a residue. The crude product compound 3 (34.9 g, crude) was used into the next stepwithout further purification. To a solution of compound 3 (34.9 g, 194 mmol, 1.0 eq.) in DMF (350 mL) wasBoc-Orn(Fmoc)-OH (88.0 g, 194 mmol, 1.0 eq.), HATU (73.6 g, 194 mmol, 1.0 eq.) and DIPEA (50.1 g, 387 mmol, 64.2 mL, 2.0 eq.) . The mixture was stirred at 25 °C for 1 hr. The reaction was monitored by LCMS 1 (MD00822-26-P1A1, Rt = 0.53 min, MS cal.: 616.7, MS observed: [M+H]+617.3) and showed compound 3 was consumed and compound 4 was detected. The reactionmixture was quenched by addition H2O 350.0 mL at 25 °C, and then diluted with DCM 700 mL and extracted with DCM 700 mL (700 mL * 3). The combined organic layers were washed with H2O 500 mL (500.0 mL * 3), filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM / MeOH=1 / 0 to 100 / 40). Compound 4 (60.4 g, 97.9 mmol, 50.5% yield) was obtained as a white solid. To a solution of compound 4 (10.9 g, 17.6 mmol, 1.0 eq.) in THF (100 mL) wasadded ZnBr2 (317 g, 1.41 mol, 70.4 mL, 80.0 eq.). The mixture was stirred at 25 °C for 90 hr. The reaction was monitored by LCMS 1 (MD00822-61- P1A9_3, Rt = 0.40 min, MS cal.: 516.6, MS observed: [M+H]+517.3) and showed compound 4 was consumed and compound 5 was detected.Concentrated under reduced pressure to give a residue. The combined organic layers were washed with ACN 500 mL (500 mL * 2), filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition) to afford compound 5 (9.44 g, 15.0mmol, 85.2% yield, TFA salt) was obtained as a white solid. To a solution of compound 4 (30.0 g, 48.6 mmol, 1.0 eq.) in DMF (150 mL)was added bis(4-nitrophenyl) carbonate (29.6 g, 97.3 mmol, 2.0 eq.) and DIPEA (12.6 g, 97.3 mmol, 16.1 mL, 2.0 eq.). The mixture was stirred at 25 °C for 2 hr. The reaction was monitored by LCMS 1 (MD00822-46-P1A1, Rt = 0.65 min, MS cal.: 781.8, MS observed: [M+H]+ 782.3) and showed compound4 was consumed and compound 6 was detected. The resulting reactionmixture was triturated with isopropyl ether (1.50 L *2), the precipitated solid was centrifuged and filtered, then the solid was dried to get the crude product. The crude product compound 6 (31.4 g, crude) was used into the next stepwithout further purification. To a solution of compound 6 (30.0 g, 38.4 mmol, 1.0 eq.) in DMF (300 mL) was added 2-aminoacetic acid (5.76 g, 76.7 mmol, 2.0 eq.), HOBt (6.22 g, 46.0 mmol, 1.2 eq.) and 4-methylmorpholine (7.76 g, 76.7 mmol, 8.44 mL, 2.0 eq.). The mixture was stirred at 25 °C for 6 hr. The reaction was monitored by LCMS 1 (MD00822-95-P1A3, Rt = 0.50 min, MS cal.: 717.7, MS observed: [M-H]+716.4) and showed compound 6 was consumed and compound 7 wasdetected. The reaction mixture was purified by prep-HPLC (neutral condition)to afford compound 7 (10.2 g, 14.2 mmol, 37.0% yield) was obtained as ayellow solid. To a solution of compound 7 (10.2 g, 14.2 mmol, 1.0 eq.) in DCM (90.0 mL)was added TFA (15.4 g, 135 mmol, 10.0 mL, 9.47 eq.). The mixture was stirred at 25 °C for 2 hr. The reaction was monitored by LCMS 1 (MD00822-106- P1A2, Rt = 0.43 min, MS cal.: 617.6, MS observed: [M-H]+616.3) and showed compound 7 was consumed and compound 8 was detected. The resultingreaction mixture was triturated with isopropyl ether (900 mL *2), the precipitated solid was centrifuged and filtered, then the solid was dried to get the crude product. The residue was purified by prep-HPLC (neutral condition) to afford compound 8 (3.70 g, 5.99 mmol, 42.2% yield) was obtained as a whitesolid. for To a solution of compound 9 (15.0 g, 39.1 mmol, 1.0 eq.) in THF (150 mL) wasadded HOSu (18.0 g, 156 mmol, 4.0 eq.) and DCC (32.3 g, 156 mmol, 31.7 mL, 4.0 eq.). The mixture was stirred at 25 °C for 1 hr. The reaction was monitored by LCMS 1 (MD00822-53-P1A1, Rt = 0.54 min, MS cal.: 577.5, MS observed: [M+H]+ 578.3) and showed compound 9 was consumed andcompound 10 was detected. Filtered and concentrated under reducedpressure to give a residue. The residue was purified by prep-HPLC (TFA condition) to afford compound 10 (20.76 g, 35.946 mmol, 91.876% yield, TFAsalt) was obtained as a white solid.To a solution of compound 10 (17.9 g, 31.0 mmol, 4.0 eq.) in DMF (180 mL)was added compound 5 (4.0 g, 7.74 mmol, 1.0 eq.) and DIPEA (2.00 g, 15.5mmol, 2.57 mL, 2.0 eq.). The mixture was stirred at 25 °C for 1 hr. The reaction was monitored by LCMS 1 (MD00822-64-P1A1, Rt = 0.59 min, MS cal.: 979.0, MS observed: [M+H]+ 980.2) and showed compound 10 was consumed andcompound 11 was detected. The reaction mixture was purified by prep-HPLC(TFA condition) to afford compound 11 (3.75 g, 3.83 mmol, 49.5% yield) wasobtained as a white solid. To a solution of compound 11 (2.44 g, 2.50 mmol, 1.0 eq.) in DMF (20.0 mL)was added compound 8 (1.85 g, 3.00 mmol, 1.2 eq.) and DIPEA (645 mg, 5.00mmol, 827 L, 2.0 eq.). The mixture was stirred at 25 °C for 1 hr. The reactionwas monitored by LCMS 1 (MD00822-86-P1A1, Rt = 0.62 min, MS cal.: 1481.2, MS observed: [M+H]+ 1482.7) and showed compound 11 wasconsumed and compound 12 was detected. The resulting reaction mixture wastriturated with isopropyl ether (200.0 mL *2), the precipitated solid was centrifuged and filtered, then the solid was dried to get the crude product. The crude product compound 12 (5.7 g, crude) was used into the next step withoutfurther purification.General procedure for preparation of compound 13 To a solution of compound 12 (5.0 g, 3.38 mmol, 1.0 eq.) in DMF (50.0 mL)was added bis(4-nitrophenyl) carbonate (5.13 g, 16.9 mmol, 5.0 eq.) and DIPEA (1.31 g, 10.1 mmol, 1.68 mL, 3.0 eq.). The mixture was stirred at 25 °C for 3 hr. The reaction was monitored by LCMS 1 (MD00822-91-P1A1, Rt = 0.73 min, MS cal.: 1767.8, MS observed: [M+H]+1768.1) and showed compound 12 was consumed and compound 13 was detected. The resultingreaction mixture was triturated with isopropyl ether (500.0 mL *2), the precipitated solid was centrifuged and filtered, then the solid was dried to get the crude product. The crude product compound 13 (8.9 g, crude) was usedinto the next step without further purification. General procedure for preparation of compound 14 To a solution of compound 13 (8.9 g, 5.04 mmol, 1.0 eq.) in DMF (45.0 mL)was added Exatecan (4.01 g, 7.56 mmol, 1.5 eq.), HOBt (1.36 g, 10.1 mmol,2.0 eq.) and DIPEA (1.30 g, 10.1 mmol, 1.67 mL, 2.0 eq.). The mixture was stirred at 25 °C for 6 hr. The reaction was monitored by LCMS 1 (MD00822- 94-P1A3_1, Rt = 4.91 min, MS c...

Claims

1. New PCT-Patent Application Araris Biotech AG Vossius Ref.: AG3709 PCT / A BS CLAIMS1. An antibody-drug conjugate (ADC) having the formula A-L, wherein A is anantibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, preferably a camptothecin cytotoxic molecule which is not cell-permeable; and as a third payload a toxin or a cytotoxin, more preferably an auristatin, and even more preferably MMAE (Monomethyl auristatin E).

2. The ADC according to claim 1, wherein the camptothecin is an exatecan.

3. The ADC according to claim 1 or 2, wherein the second payload has beenmodified to reduce its cell permeability.

4. The ADC according to any one of claims 1 to 3, wherein the second payloadhas a glycine residue linked to said topoisomerase I inhibitor of the second payload.

5. The ADC according to any one of claims 1 to 4, wherein the linker is a peptidelinker.

6. The ADC according to claim 5, wherein the first payload and / or second payloadare linked to the N- or C-terminus of the peptide linker or to a side-chain of an amino acid residue comprised in the peptide linker; preferably wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker, or vice versa.

7. The ADC according to any of claim 1 to 6, wherein the linker is conjugated tothe antibody via an isopeptide bond formed between a glutamine residue comprised in the antibody and a primary amine comprised in the linker,preferably wherein the primary amine is comprised in a lysine residue, a lysine mimetic or a lysine derivative comprised in a peptide linker or wherein the primary amine is comprised in an amino acid residue having the structure NH2- (CH2)1-10-COOH comprised in a peptide linker.

8. The ADC according to any one of claims 1 to 7, wherein the linker furthercomprises at least one positively charged amino acid residue, preferably wherein the at least one positively charged amino acid residue is selected from arginine and / or histidine.

9. The ADC according to any one of claims 1 to 8, wherein the linker comprisesthe following structure: [payload1]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 2]; or [payload2]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2; and X is either absent or a self-immolative group, preferably PABC.

10. The ADC according to claim 9, wherein (Aa)m + (Aa)n + (Aa)o is > 0, preferablywherein (Aa)n+ (Aa)ois > 0.

11. The ADC according to claim 9 or 10, wherein Z2 is a dicarboxylic acid linkingthe N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and wherein one payload is directly or indirectly linked to the C-terminal end of (Aa)mand the other payload is directly or indirectly linked to the C-terminal end of (Lys) or (Aa)o, or vice versa.

12. The ADC according to any one of claims 9 to 11, wherein the linker comprisesthe following structure: [payload1]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 2]; or [payload2]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 1];wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m is an integer ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.

13. The ADC according to any one of claims 9 to 12, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).

14. The ADC according to any one of claims 9 to 13, wherein (Aa)n-(Lys)-(Aa)o isor comprises the sequence motif RK or RKAA (in N -> C direction).

15. The ADC according to any one of claims 1 to 14, wherein said ADC comprisesmore than one first payloads and / or more than one second payloads.

16. The ADC according to any one of claims 1 to 15, wherein the linker is a peptidelinker and wherein the third payload is linked to the N- or C-terminus of the peptide linker or wherein the third payload is linked to a side chain of an amino acid residue comprised in the peptide linker.

17. The ADC according to claim 16, wherein two payloads are linked to the samefunctional group of the peptide linker, preferably via a chemical linker comprising a disubstituted amine.

18. The ADC according to claim 17, wherein the linker consists of or comprisesthe structure: (X- [payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X- [payload])2;or([payloa1-6- C(=O)-(Aa)p / p*-Z3-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2, even more preferably wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, preferably PABC.

19. The ADC according to claim 18, wherein (Aa)n + (Aa)o is > 0.

20. The ADC according to any one of claims 17 to 19, wherein the linker consistsof or comprises the structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- X-[payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)- (Aa)p / p*-X-[payload])2;or ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- N-((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.

21. The ADC according to any one of claims 18 to 20, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).

22. The ADC according to any one of claims 18 to 21, wherein (Aa)n-(Lys)-(Aa)o isor comprises the sequence motif RK or RKAA (in N -> C direction).

23. The ADC according to any one of claims 1 to 22, wherein the linker comprisesor consists of the following structure:

24. The ADC according to any one of claims 1 to 23, wherein the antibody is anIgG antibody, preferably an IgG1 or IgG4 antibody.

25. The ADC according to any one of claims 7 to 24, wherein the glutamine residueis residue Q295 (EU numbering) of the CH2 domain of an IgG antibody.

26. The ADC according to any one of claims 1 to 25, wherein the antibody is aglycosylated antibody, preferably wherein the antibody is an IgG antibody glycosylated at residue N297 (EU numbering).

27. The ADC according to any one of claims 1 to 26,wherein the antibody is selected from the group consisting of: Trastuzumab, Brentuximab, , Gemtuzumab, Inotuzumab, Avelumab, Cetuximab, Rituximab, Daratumumab, Pertuzumab, Vedolizumab, Ocrelizumab, Tocilizumab, Ustekinumab, Golimumab, Obinutuzumab, Sacituzumab, Belantamab, Polatuzumab, Enfortumab, Endrecolomab, Gemtuzumab,Loncastuximab,Mecbotamab, Adecatumumab, D93, Gatipotuzumab, Labetuzumab, Tusamitamab, Upifitamab, Lifastuzumab, Mirvetuximab, Sofituzumab, Anetumab, Tisotumab, Cofituzumab, Praluzatamab, Ladriatuzumab, Belantamab, Patritumab, Cetuximab, Nimotuzumab, Matuzumab, Portuzumab, Citatuzumab, Tucotuzumab, Endrecolomab and Indatuximab; and / or wherein the antibody specifically binds to an antigen selected from the group consisting of: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38, HER2, Integrin 4 7, CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA,CD79b, Nectin-4, EpCAM, CD33, CD19, AXL, dn-collagen, TA-MUC1, carcinoembryonic cell adhesion molecule 5, CEACAM5, NaPi2b, FR ,MUC16, mesothelin, TF, CD166, LIV-1, ERBB3, EGFR, TACSTD1, Claudin 18.2, CLDN1, CLDN6, CLDN9, EphA2, B7H4, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, Cadherin17, ST14, P-cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG-72, FGFRs (e.g. FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 (CD318), GPCR5A, GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4.

28. A pharmaceutical composition comprising the ADC according to any one ofclaims 1 to 27 and at least one pharmaceutically acceptable ingredient.

29. The ADC according to any one of claims 1 to 27 or the pharmaceuticalcomposition of claim 28 for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease, in particular wherein the neoplastic disease is cancer.

30. The ADC according to any one of claims 1 to 27 and 29 or the pharmaceuticalcomposition of claim 28 or 29, wherein the antibody-payload conjugate comprises Trastuzumab and wherein the neoplastic disease is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; wherein the antibody-payload conjugate comprises Polatuzumab and wherein the neoplastic disease is a B-cell associated cancer; preferably, wherein the B-cell associated cancer is non-Hodgkin lymphoma, in particular wherein the B-cell associated cancer is diffuse large B-cell lymphoma; or wherein the antibody-payload conjugate comprises Enfortumab or an Enfortumab variant and wherein the neoplastic disease is a Nectin-4 positivecancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer.

31. The ADC according to any one of claims 1 to 27 and 29 or the pharmaceuticalcomposition of claim 28 or 29, wherein the antibody-payload conjugate comprises an antibody targeting NaPi2b, preferably wherein the antibody targeting NaPi2b is Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99, or with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101, and wherein the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer.

32. The ADC according to any one of claims 1 to 27 and 29 or the pharmaceuticalcomposition of claim 28 or 29, wherein the antibody-payload conjugate comprises an antibody targeting Nectin-4, preferably wherein the antibody targeting Nectin-4 is m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97, or Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77, and wherein the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer, preferably wherein the ADC comprises a linker having the structure:

33. A linker comprising a first, a second, and a third payload, wherein the firstpayload is a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; wherein the second payload is a topoisomerase I inhibitor which is not cell- permeable, preferably a camptothecin cytotoxic molecule which is not cell- permeable; andwherein the third payload is a toxin or a cytotoxin, more preferably an auristatin, and even more preferably MMAE (Monomethyl auristatin E); preferably wherein the linker is for conjugation to an antibody.

34. The linker according to claim 33, wherein the camptothecin is exatecan or DXd.

35. The linker according to claim 33 or 34, wherein the second payload has beenmodified to reduce its cell permeability.

36. The linker according to any one of claims 33 to 35, wherein the second payloadhas a glycine residue linked to said topoisomerase I inhibitor of the second payload.

37. The linker according to any one of claims 33 to 36, wherein the linker is apeptide linker.

38. The linker according to claim 37, wherein the first payload and / or secondpayload are linked to the N- or C-terminus of the peptide linker or to a side- chain of an amino acid residue comprised in the peptide linker; preferably wherein the first payload is linked to the N-terminus of the peptide linker and wherein the second payload is linked to the C-terminus of the peptide linker, or vice versa.

39. The linker according to any of claim 33 to 38, wherein the linker comprises aprimary amine for conjugation to an antibody, preferably wherein the primary amine is comprised in a lysine residue, a lysine mimetic or a lysine derivative; or wherein the primary amine is comprised in an amino acid residue having the structure NH2-(CH2)1-10-COOH; preferably wherein the amino acid residues are comprised in a peptide linker.

40. The linker according to any one of claims 33 to 39, wherein the linker furthercomprises at least one positively charged amino acid residue, preferably wherein the at least one positively charged amino acid residue is selected from arginine and / or histidine.

41. The linker according to any one of claims 33 to 40, wherein the linkercomprises the following structure: [payload1]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 2]; or[payload2]-X-Z1-(Aa)m-Z2-(Aa)n-(Lys)-(Aa)o-Z3-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m, n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2; and X is either absent or a self-immolative group, preferably PABC.

42. The linker according to claim 41, wherein (Aa)m + (Aa)n + (Aa)o is > 0,preferably wherein (Aa)n+ (Aa)ois > 0.

43. The linker according to claim 41 or 42, wherein Z2 is a dicarboxylic acid linkingthe N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and wherein one payload is directly or indirectly linked to the C-terminal end of (Aa)mand the other payload is directly or indirectly linked to the C-terminal end of (Lys) or (Aa)o, or vice versa.

44. The linker according to any one of claims 41 to 43, wherein the linkercomprises the following structure: [payload1]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 2]; or [payload2]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-X-[payload 1]; wherein [payload 1] is said first payload; [payload 2] is said second payload; (Aa) is any amino acid residue; m is an integer ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mto the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.

45. The linker according to any one of claims 41 to 44, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).

46. The linker according to any one of claims 41 to 45, wherein (Aa)n-(Lys)-(Aa)ois or comprises RK or RKAA (in N -> C direction).

47. The linker according to any one of claims 33 to 46, wherein the linker is apeptide linker and wherein the third payload is linked to the N- or C-terminus of the peptide linker or wherein the third payload is linked to a side chain of an amino acid residue comprised in the peptide linker.

48. The linker according to claim 47, wherein two payloads are linked to the samefunctional group of the peptide linker, preferably via a chemical linker comprising a disubstituted amine.

49. The linker according to claim 48, wherein the linker consists of or comprisesthe structure: (X- [payload]; or [payload]-X-Z1-(Aa)m-Z2-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)-(Aa)p / p*-Z3-X- (1-6- C(=O)-(Aa)p / p*-Z3-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, n, o, p and p* may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; Z1-3is either absent or a spacer comprising an alkyl or a heteroalkyl group, preferably wherein the spacer comprises (CH2)2, even more preferably wherein Z2is a dicarboxylic acid linker; and X is either absent or a self-immolative group, preferably PABC.

50. The linker according to claim 49, wherein (Aa)n + (Aa)o is > 0.

51. The linker according to any one of claims 48 to 50, wherein the linker consistsof or comprises the structure: ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- X-[payload]; or [payload]-X-(Aa)m-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o-N-((CH2)1-6-C(=O)- (Aa)p / p*-X-[payload])2;or ([payload]-X-(Aa)m / m*-C(=O)-(CH2)1-6)2-N-(dicarboxylic acid)-(Aa)n(Lys)-(Aa)o- N-((CH2)1-6-C(=O)-(Aa)p / p*-X-[payload])2wherein [payload] is each independently a payload selected from the first, second and third payload, wherein the linker comprises all three payloads; (Aa) is any amino acid residue; m, m*, p and p* are integers ranging from 1 to 10, preferably 1 to 6, more preferably 1 to 4; n and o may be integers ranging from 0 to 10, preferably 0 to 6, more preferably 0 to 4, wherein n+o is >0; (Lys) is a lysine residue, a lysine mimetic or a lysine derivative; (dicarboxylic acid) is dicarboxylic acid linking the N-terminal end of (Aa)mor the disubstituted amine (N) to the N-terminal end of (Aa)nor (Lys); and X is either absent or a self-immolative group, preferably PABC.

52. The linker according to any one of claims 49 to 51, wherein (Aa)n-(Lys)-(Aa)ocomprises the sequence motif Arg-Lys (RK) or His-Lys (HK) (in N -> C direction).

53. The linker according to any one of claims 49 to 52, wherein (Aa)n-(Lys)-(Aa)ois or comprises RK or RKAA (in N -> C direction).

54. The linker according to any one of claims 47 to 53, wherein the linkercomprises or consists of the following structure:

55. A method for the preparation of an antibody-drug conjugate comprising a stepof conjugating a peptide linker according to any of claims 33 to 54 to an antibody.

56. A method for the conjugation of a peptide linker according to any one of claims37 to 54 to an antibody using a transglutaminase (TG), the method comprising a) mixing the antibody, the peptide linker and a transglutaminase (TG) within a fluid, thereby conjugating the linker-payload to the antibody in one step under the catalyzing effect of the TG, and b) extracting the conjugate obtained in step a) from the fluid.

57. The method according to claim 56, wherein the peptide linker is conjugated toa glutamine residue comprised in the antibody via a primary amine comprised in an amino acid residue of the peptide linker.

58. The method according to claim 56 or 57, wherein the peptide linker isconjugated to a glutamine residue comprised in an Fc domain of an IgG antibody.

59. The method according to claim 57 or 58, wherein the glutamine residue towhich the peptide linker is conjugated is glutamine residue Q295 (EU numbering) of the CH2 domain of an IgG antibody.

60. The method according to any one of claims 56 to 59, wherein the antibody isa glycosylated IgG antibody.

61. The method according to claim 60, wherein the IgG antibody is glycosylated atresidue N297 (EU numbering) of the CH2 domain.

62. The method according to any one of claims 56 to 61, wherein the antibody isselected from the group consisting of: m290, Trastuzumab, Brentuximab, , Gemtuzumab, Inotuzumab, Avelumab, Cetuximab, Rituximab, Daratumumab, Pertuzumab, Vedolizumab, Ocrelizumab, Tocilizumab, Ustekinumab, Golimumab, Obinutuzumab, Sacituzumab, Belantamab, Polatuzumab, Enfortumab, Endrecolomab, Gemtuzumab,Loncastuximab, Mecbotamab, Adecatumumab, D93, Gatipotuzumab, Labetuzumab, Tusamitamab, Upifitamab, Lifastuzumab, Mirvetuximab, Sofituzumab, Anetumab, Tisotumab, Cofituzumab, Praluzatamab, Ladriatuzumab, Belantamab, Patritumab, Cetuximab, Nimotuzumab, Matuzumab, Portuzumab, Citatuzumab, Tucotuzumab, Endrecolomab and Indatuximab; and / or wherein the antibody specifically binds to an antigen selected from the group consisting of: CD30, Her2 / neuCD33, CD22, PD-L1, EGFR, CD20, CD38, HER2, Integrin 4 7, CD20, IL-6-R, IL-12, IL-23, TNF , CD20, Trop-2, BCMA,CD79b, Nectin-4, EpCAM, CD33, CD19, AXL, dn-collagen, TA-MUC1, carcinoembryonic cell adhesion molecule 5, CEACAM5, NaPi2b, FR ,MUC16, mesothelin, TF, CD166, LIV-1, ERBB3, EGFR, TACSTD1, Claudin 18.2, CLDN1, CLDN6, CLDN9, EphA2, B7H4, c-MET, LGR5, LGR4, LGR6, RNF43, NOX1, CD334, B7H3, Cadherin17, ST14, P-cadherin, LY6G6D, GPA33, Syndecan-1 (CD138), dsGAG, TAG-72, FGFRs (e.g. FGFR2b, FGFR3), CEACAM6, PSMA, LRRC15, CDCP1 (CD318), GPCR5A, GPCR5D, and H type glycans, preferably, CD30, Her2 / neu, CD22, CD79b, Nectin-4, Trop-2 and BCMA, more preferably, CD79b, Her2 / neu, and Nectin-4.

63. The method according to any one of claims 56 to 62, wherein the peptide linkeris suitable for conjugation to a glycosylated antibody with a conjugation efficiency of at least 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90% or 95%.

64. The method according to any one of claims 56 to 63, wherein thetransglutaminase is a microbial transglutaminase (MTG), preferably wherein the microbial transglutaminase is derived from a Streptomyces species, inparticular Streptomyces mobaraensis.

65. A method of treating cancer in a subject in need, comprising administering tothe subject (an effective amount of) an ADC according to any one of claims 1 to 27 or a pharmaceutical composition according to claim 28.

66. The method of claim 65, wherein:the ADC comprises Trastuzumab and the cancer is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; or the ADC comprises Polatuzumab and the neoplastic disease is a B-cell associated cancer, preferably non-Hodgkin lymphoma, in particular diffuse large B-cell lymphoma; or the ADC comprises Enfortumab or an Enfortumab variant and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer.

67. The method of claim 65, wherein the ADC comprises an antibody targetingNaPi2b, preferably Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99, or with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101, and the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer.

68. The method of claim 65, wherein the ADC comprises an antibody targetingNectin-4, preferably m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97, or Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77, and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer, preferably wherein the ADC comprises a linker having the structure:

69. Use of an ADC according to any one of claims 1 to 27 or a pharmaceuticalcomposition according to claim 28 in the manufacture of a medicament for the treatment of cancer in a subject in need.

70. The use according to claim 69, wherein:the ADC comprises Trastuzumab and the cancer is a HER2-positive cancer, in particular HER2-positive breast, gastric, ovarian or lung cancer; or the ADC comprises Polatuzumab and the neoplastic disease is a B-cell associated cancer, preferably non-Hodgkin lymphoma, in particular diffuse large B-cell lymphoma; or the ADC comprises Enfortumab or an Enfortumab variant and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer.

71. The use according to claim 69, wherein the ADC comprises an antibody targeting NaPi2b, preferably Upifitamab with a heavy chain as set forth in SEQ ID NO:98 and a light chain as set forth in SEQ ID NO:99, or with a heavy chain as set forth in SEQ ID NO:100 and a light chain as set forth in SEQ ID NO:101, and the neoplastic disease is a NaPi2b positive cancer, in particular NaPi2b positive lung or ovarian cancer.

72. The use according to claim 69, wherein the ADC comprises an antibody targeting Nectin-4, preferably m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97, or Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77, and the neoplastic disease is a Nectin-4 positive cancer, in particular Nectin-4 positive pancreatic cancer, lung cancer, bladder cancer or breast cancer, preferably wherein the ADC comprises a linker having the structure:

73. An antibody-drug conjugate (ADC) having the formula A-L, wherein A is anantibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a camptothecin cytotoxic molecule which is cell-permeable;as a second payload a camptothecin cytotoxic molecule which is not cell- permeable; wherein the cytotoxic molecule of the first and second payload is an exatecan; wherein the second payload has a glycine residue linked to said camptothecin cytotoxic molecule of the second payload; and as a third payload an auristatin, preferably an MMAE; wherein said ADC consists of two first payloads, two second payloads and two third payloads (drug-to-antibody ratio of 6 “DAR6”); and wherein said antibody is an IgG, preferably, an IgG1 antibody.

74. The ADC according to claim 65, wherein the antibody is m290.

75. An antibody-drug conjugate comprising:a) an antibody targeting Nectin-4, preferably m290 with a heavy chain as set forth in SEQ ID NO:96 and a light chain as set forth in SEQ ID NO:97; and; wherein the linker is conjugated to the antibody via an isopeptide bond formed between glutamine residue Q295 (EU numbering) of the CH2 domain of the antibody and a primary amine comprised in the lysine residue comprised in the RK sequence motif of the linker.

76. An antibody-drug conjugate comprising:a) an antibody targeting Nectin-4, preferably Enfortumab with a heavy chain as set forth in SEQ ID NO:75 or 94 and a light chain as set forth in SEQ ID NO:95, 76 or 77; and b) a linker having the structure:; wherein the linker is conjugated to the antibody via an isopeptide bond formed between glutamine residue Q295 (EU numbering) of the CH2 domain of the antibody and a primary amine comprised in the lysine residue comprised in the RK sequence motif of the linker.

77. A pharmaceutical composition for treating cancer comprising the ADCaccording to claim 75 or 76.

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