CD16a-binding polypeptide

Abstract

The invention provides a CD16a-binding polypeptide which comprises at least one motif that binds to CD16a, and wherein said CD16a-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], the CD16a-binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]; wherein the CD16a-binding motif sequence is: QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1). The invention also provides a CD16a-binding polypeptide which comprises at least one motif that binds to CD16a, and wherein said CD16a-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], the CD16a-binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]; wherein the sequence of the CD16a-binding polypeptide is: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2). The invention also provides a CD16a-binding polypeptide which comprises the following structure: [BCMA-binding polypeptide]-[Linker 1]-[BCMA-binding polypeptide]-[Linker 2]-[CD16a-binding polypeptide], wherein: each of the BCMA-binding polypeptides comprises the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 4); the CD16a-binding polypeptide comprises the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or comprises the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 has the sequence (GGGSG)n, where n is 1, 2 or 3. The invention further provides CD16a binder-drug conjugates and pharmaceutical compositions comprising the CD16a-binding polypeptide and the use of the CD16a-binding polypeptide, CD16a binder-drug conjugate or pharmaceutical composition in medicine, particularly the treatment of cancer such as multiple myeloma.

Description

[0001] Novel polypeptides Field of the Invention The present invention relates to immune cell-engaging polypeptides comprising aCD16a-binding polypeptide, immune cell-engaging polypeptides comprising a CD16a-binding polypeptide and at least one additional functional portion, or immune cell-engaging polypeptides comprising a CD16a-binding polypeptide comprising at leasttwo CD16a-binding polypeptides and optionally at least one additional functionalportion. The present invention also relates to pharmaceutical compositionscomprising said immune cell-engaging polypeptides, and their use in the treatment and / or prophylaxis of cancer. Background of the Invention Immunotherapy has proven to be an effective treatment of several cancers with approved therapies constituting monoclonal and bispecific antibodies, immunomodulatory drugs and CAR-T treatments. Despite activity of these treatments, however, some patients exhibit very short responses or fail to respond to treatment. Side effects from some immunotherapies can be severe, especially side effects related to an exacerbated cytokine release. Indeed, cytokine release syndrome is one of the most common serious adverse effects of T cell-engaging immunotherapeutic agents (Shimabukuro-Vornhagen A et al. Cytokine releasesyndrome. J Immunother Cancer. 2018;6(1):56. doi:10.1186 / s40425-018-0343-9).Many patients will also, eventually, become resistant to available treatments. Thus despite recent advances, there is still a need for additional treatment options in cancer immunotherapy. One apparent obstacle with current treatment modalities is suboptimal distribution to tumorous tissue. Rates of tissue distribution are negatively correlated with molecular size, and so larger molecules such as antibodies have less efficient tumour penetration than smaller ones. Another issue is immune evasion by cancer cells, which often involves inhibitory immune signals in the tumour environment. Examples of such signals include: the production of immunosuppressive cytokines and other molecules, such as TGFβ or VEGF; cell-mediated immunosuppression, e.g. via tumour-derived regulatory T cells; modulation of antigen presentation and MHCI expression; or altered expression of other ligands, e.g. increased expression of inhibitory checkpoint ligands (such as Programmed death-ligand 1 (PD-L1) and HLA- E), which reduces tumour cell killing by CD8+ T cells and natural killer (NK) cells (Vinay D et al, Immune evasion in cancer: Mechanistic basis and therapeutic strategies, Seminars in Cancer Biology.2015:35 (Supplement):S185, https: / / doi.org / 10.1016 / j.semcancer.2015.03.004; Ben-Shmuel A et al, UnleashingNatural Killer Cells in the Tumor Microenvironment - The Next Generation ofImmunotherapy? Front Immunol.2020;11:275, doi:10.3389 / fimmu.2020.00275). NK cells are a component of the innate immune system whose functions includecytokine secretion and cell killing via secretion of perforin- and granzyme-containingcytolytic granules. They are capable of antibody-dependent cellular cytotoxicity(ADCC) when target cells, such as tumour cells, are bound by IgG antibodies. Bindingof the Fc antibody region to the CD16 receptor (FCγRIII) on NK cells overrides inhibitory signals, triggering cytokine secretion and lysis of the target cell (Vivier E et al., Functions of natural killer cells, Nat Immunol.2008;9:503, https: / / doi.org / 10.1038 / ni1582; Pallmer K and Oxenius A, Recognition and regulation of T cells by NK cells, Front Immunol 2016, 7:251, doi: / 10.3389 / fimmu.2016.00251). CD16 is expressed in two forms, CD16a and CD16b, which vary in their expression patterns and affinities for IgG Fc. CD16a is the form predominantly expressed on NK cells, as well as being found on monocytes. CD16b, in contrast, is mostly found on neutrophils, though its expression can also be induced on eosinophils. Despite the high degree of sequence similarity (around 96%) between CD16a and CD16b, CD16a has a much higher binding affinity for IgG. (Roberts JT and Barb AW, A single amino acid distorts the Fc γ receptor IIIb / CD16b structure upon binding immunoglobulin G1 and reduces affinity relative to CD16a, J Biol Chem.2018;293(51):19899-19908,doi:10.1074 / jbc.RA118.005273). Genotypic variation of the CD16a (FcγRIIIa) receptoritself can also alter its binding affinity: the FcγRIIIa-176V / F polymorphism (rs396991) (in some publications where the leader sequence is excluded, position 176 is reported as position 158 and this numbering is also used in the Examples herein) results in either a valine (V) or phenylalanine (F) at position 176, giving rise to variable binding phenotypes (F / F: low affinity; V / V or V / F: high affinity, and therefore higher NK cell-mediated ADCC). (Chong KT et al., Distribution of the FcγRIIIa 176 F / V polymorphism amongst healthy Chinese, Malays and Asian Indiansin Singapore, Br J Clin Pharmacol 2006;63(3): 328-332, doi: 10.1111 / j.1365-2125.2006.02771.x). Recently, there has been increasing interest in harnessing the NK cell response for cancer immunotherapy. These include use of checkpoint inhibitor blockers, the ex vivo expansion and administration of NK cells, production of CAR-NK cells (analogousto CAR-T cell therapies), and the use of bi- or multivalent NK cell engagers that cross-link NK cells to cancer cells expressing specific antigens (Hofer E and Koehl U, Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies, Front Immunol.2017;8:745, doi: / 10.3389 / fimmu.2017.00745).Antibody-based NK engagers under development include Affimed’s AFM13 (an anti-CD16a / CD30 tetravalent bispecific antibody) and AFM24 (an anti-CD16a / EGFR IgG1- scFv fusion antibody). Both AFM13 and AFM24 have additionally been tested for their ability to induce tumour cell killing by macrophages via antibody-dependent cellular phagocytosis (ADCP) (Wingert S et al, Preclinical evaluation of AFM24, a novel CD16A-specific innate immune cell engager targeting EGFR-positive tumors. mAbs.2021;13(1):1950264. doi:10.1080 / 19420862.2021.1950264; Wingert S et al, CD16A-Specific Tetravalent Bispecific Immune Cell Engagers Potently Induce Antibody-Dependent Cellular Phagocytosis (ADCP) on Macrophages, Blood 2018;132(Supplement 1):1111, doi: / org / 10.1182 / blood-2018-99-118427). Other bi- and multivalent NK engagers include the camelid VHH antibody-derived BiKEs andTriKEs, such as GT Biopharma’s GTB-3650 which contains CD33- and CD16a-targetingregions joined to the costimulatory molecule IL15. A further bispecific cell engager under development is RO7297089. RO7297089 is a bispecific tetravalent antibody targeting CD16a and BCMA (B-Cell Maturation Antigen). BCMA is highly expressed on multiple myeloma (MM). The properties ofthe antibody compound were described in Kakiuchi-Kiyota et al. (Leukemia (2022)36:1006–1014; doi: / org / 10.1038 / s41375-021-01478-w). The findings from a Phase Idose-escalation study of RO7297089 in patients with Relapsed / Refractory MultipleMyeloma (Study registration NCT04434469) were reported by Plesner et al. (PosterAbstract 2755, Session 653, American Society of Hematology (ASH) Conference, 12 December 2021). Despite this progress, antibody-derived NK engagers still share the inherent difficulties associated with existing antibody cancer therapeutics, especially with regard to immunogenicity and tissue penetration. There therefore remains a need for improved cancer immunotherapeutics that can be delivered more efficiently to the tumour, while retaining the target specificity of antibodies and antibody-based drugs and avoiding potential side-effects. The present invention seeks to address the aforementioned needs. Summary of the InventionThe present invention provides a CD16a-binding polypeptide which comprises atleast one motif that binds to CD16a, and wherein said CD16a-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a-binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]; wherein the CD16a-binding motif sequence is: QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1).The present invention also provides a CD16a-binding polypeptide which comprises atleast one motif that binds to CD16a, and wherein said CD16a-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a-binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]; wherein the sequence of the CD16a-binding polypeptide is: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2). The present invention further provides a CD16a-binding polypeptide which comprises the following structure: [BCMA-binding polypeptide]-[Linker 1]-[BCMA-binding polypeptide]-[Linker 2]-[CD16a-binding polypeptide] wherein: each of the BCMA-binding polypeptides comprises the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide comprises the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or comprises the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 has the sequence (GGGSG)n, where n is 1, 2 or 3. The present inventors have surprisingly found that CD16a-binding polypeptides of the invention based on a non-antibody scaffold are effective in engaging NK cells and triggering ADCC-mediated cancer cell killing. Such CD16a-binding polypeptides are especially effective in engaging NK cells and triggering ADCC-mediated cancer cellkilling. They are also especially effective at inhibiting tumour growth in vivo incombination with administration of NK cells. The present inventors have also surprisingly found that CD16a-binding polypeptides of the invention show negligible non-specific NK cell and CD16a activation in the absence of target cells, and show high specificity for their primary targets. CD16a- binding polypeptides of the invention are additionally stable in human plasma. They also advantageously do not compete with IgG, meaning that the specific response of such polypeptides against a tumour associated target is unlikely to be dampened by endogenous IgG. The present inventors have further found that heterotrimeric CD16a-binding polypeptides of the invention, which are hBCMA x hCD16a dual engagers (i.e. comprise two additional functional portions which are binding moieties specific forhBCMA), are especially effective in triggering ADCC-mediated cancer cell killing andcompare favourably with corresponding heterodimeric hBCMA x hCD16a dual engagers. In addition, this benefit is particularly pronounced for heterotrimeric CD16a-binding polypeptides of the invention compared to comparator heterotrimeric CD16a-binding polypeptides described elsewhere. The invention therefore provides novel CD16a engagers that show promise as an anti-cancer immunotherapeutic.The invention also provides a CD16a binder-drug conjugate comprising a CD16a-binding polypeptide and an additional therapeutic agent.The invention also provides a pharmaceutical composition comprising a CD16a-binding polypeptide, or CD16a binder-drug conjugate of the invention.The invention further provides a CD16a-binding polypeptide, a CD16a binder-drugconjugate, or pharmaceutical composition of the invention for use in medicine, in particular in the treatment of a cancer.The invention also provides the use of a CD16a-binding polypeptide, CD16a binder-drug conjugate, or pharmaceutical composition of the invention for the manufacture of a medicament for the treatment of cancer. The invention also provides a method of treating cancer in which the methodcomprises administering to a patient in need thereof a CD16a-binding polypeptide,CD16a binder-drug conjugate, or pharmaceutical composition of the invention.The invention further provides a kit comprising a CD16a-binding polypeptide, CD16abinder-drug conjugate, or pharmaceutical composition of the invention and,optionally, one or more further therapeutic agent(s). Such a kit finds particular use in the treatment and / or prophylaxis of cancer. Description of the DrawingsFigure 1 shows a schematic domain construction of the binding polypeptidesdescribed in the present disclosure.Figure 2 shows the results of the CD16 activation Jurkat-Lucia™ Luciferase reporterassay of Biological Example 2 (responses were normalized to the maximal responseof elotuzumab).Figure 3 shows the results of the Calcein-release-based in vitro cytotoxicity assay.Figure 4 shows the structures (i.e. the ([hBCMA N-terminal portion]-[Helix 1]- hBCMASeparating portion]-[hBCMA Helix 2]-[ hBCMA C-terminal portion] sequences) ofhBCMA-binding polypeptide functional portions.Figure 5 shows the sequences of hBCMA-binding motifs (i.e. the [hBCMA Helix 1]-[Separating portion]-[hBCMA Helix 2] sequence) of example hBCMA binding polypeptide functional portions.Figure 6 shows the results of the CD16 activation Jurkat-Lucia™ Luciferase reporterassay of Biological Example 4 where responses in the presence or absence of excess IgG are evaluated for: (a) Q1 engager (SEQ ID NO: 5); (b) a belantamab biosimilar; and (c) elotuzumab.Figure 7 shows the results of tumour growth of MM.1S cells at day 27 (a) and day 33(b) in an in vivo model using the NSG-Tg(Hu-IL15) Jackson (NOD.C8-PrkdcscidIl2rgtm1Wjl Tg(IL15)1Sz / SzJ) mouse described in Biological example 5.Figure 8 shows the results from the NK cell activation assay of Biological example 7where the number of CD107a+ (Figure 8 a and c) and IFNγ+ NK cells (Figure 8 b andd) were analysed by flow cytometry.Figure 9 shows the structures of synthetic heterodimeric engagers produced inPreparative Example 16, including (a) schematic drawings of hBCMA and hCD16a functional portions; b) schematic of synthetic dimeric constructs; (c) structure of hCD16a x hBCMA synthetic dual engager dimeric constructs of Preparative Example 16.Figure 10 shows the fold increase in efficacy for heterotrimeric dual engagers of theinvention as compared to a corresponding heterodimeric dual engager. Comparisonis with both recombinant and synthetic produced heterodimeric dual engagers.Detailed Description The present inventors have found that polypeptides as disclosed herein are effectivebinders of CD16a and effectively engage immune cells. The polypeptides have beenfound to trigger strong ADCC responses against cancer cells in an in vitro model. Notably, the inventors have found that such anti-cancer responses compare favourably in the model with those obtained using the monoclonal antibodyelotuzumab, which is approved for treatment of multiple myeloma. The polypeptideshave also been found to induce strong killing of cancer cells in an in vitro model. Theinventors have further found that such anti-cancer responses compare favourably in the model with those obtained using an anti-BCMA targeting multiple myeloma antibody. The inventors have additionally found that a CD16a-binding polypeptide disclosedherein is highly effective at inhibiting tumour growth in vivo, in combination withadministration of NK cells, in a mouse model of multiple myeloma. The inventors have also found that, in the absence of target cells, the polypeptides disclosed herein show negligible non-specific activation of NK cells in an in vitro cell-based assay and negligible non-specific activation of CD16a in an in vitro ADCCmodel. The extremely low level of non-specific responses compares favourably in the cell-based assay and the model with the non-specific response levels observed for comparator polypeptides. This advantage is further supported by the inventors’ findings that a polypeptide disclosed herein shows high specificity for its primary targets and no off-target binding interactions in a library screen. Such a high target specificity and reduced non-specific response in the absence of target cells means that the polypeptides disclosed herein are less likely to have potentially harmful off- target effects in patients. The inventors have further found that CD16a-binding polypeptides disclosed herein are advantageously stable in human plasma. The inventors have also found the polypeptides do not compete with IgG, meaning that the specific response of such polypeptides against a tumour associated target is unlikely to be dampened by endogenous IgG. The lack of competition with IgG for polypeptides disclosed herein compares favourably with results for an anti-SLAMF7 monoclonal antibody used inmultiple myeloma treatment and an anti- BCMA monoclonal antibody targetingmultiple myeloma. The various elements of the polypeptides of the invention will now be described in further detail: Overall structureThe polypeptides of the present invention may be based on three-helix scaffolds,sometimes referred to as ‘affibodies’. Affibodies are small (around 6.5 kDa) engineered affinity ligands, based on the Z-domain polypeptide, which is a mutated version of the B-domain in the immunoglobulin-binding region of staphylococcal protein A (Nord K et al., Binding proteins selected from combinatorial libraries of an α-helical bacterial receptor domain, Nature Biotech, 1997:15:772, doi:10.1038 / nbt0897-772). In a full length affibody, the C-terminal portion includes [Second separating portion]-[Helix 3]-[C-terminal sequence]. The general structure of an affibody is shown in Figure 1. The portions of the molecules of the invention referred to as Helix 1 and Helix 2 (and Helix 3, when present) are generally helical in structure. In some rare embodiments, it can be found that the structure established by the sequence with particular residues can be not strictly helical. Such compounds are to be considered within the broadest aspect of the invention. More preferably, the residues in the Helix 1 and Helix 2 portions do result in those structures being helical, in the sense of being alpha-helical. Sequences of the polypeptides of the invention The sequence of the CD16a-binding polypeptides as disclosed herein may be expressed in terms of their constituent amino acids or in terms of nucleic acid sequences encoding polypeptides having those amino acid sequences. In the context of the present disclosure, the term “amino acid” encompasses any naturally occurring amino acid or unnatural amino acid. The term “unnatural amino acid” as used herein refers to non-proteinogenic (i.e. non-encoded) amino acids, which may either be found in nature or are chemically synthesised (for example citrulline, hydroxyproline, beta-alanine, ornithine, norleucine, 3-nitrotyrosine, pyroglutamic acid, nitroarginine, homoleucine or tert-butylalanine). The term “amino acid” includes α, β, γ and δ amino acids. It includes an amino acid in any chiral configuration. The amino acid may, especially, be a naturally occurring α amino acid. The amino acid may, especially, be a naturally occurring L amino acid. The amino acid may, especially, be a naturally occurring L-α amino acid. Within a polypeptide chain (for example a CD16a-binding polypeptide as disclosed herein), the amino acids are linked by peptide bonds between the carboxyl group of one amino acid and the amine group of the next amino acid in the chain. An individual amino acid is called a “residue” or “amino acid residue” once it is linked in a polypeptide chain. The amino acid sequences herein are shown with the N-terminus to the left, and where sequences are set out across multiple lines, the N-terminus is to the top left. Unless indicated otherwise, the amino acid residues in the sequences are L-amino acids. The amino acid sequences listed in the application are shown using standard letter abbreviations for amino acids. The specific sequences given herein relate to specific embodiments of the invention. The present disclosure also includes derivatives of all the sequences described herein (for example, derivatives of each of the CD16a-binding polypeptide and CD16a- binding oligomer sequences described herein). Derivatives of the sequences described herein are preferably derivatives wherein from 1 to 5 (for example 1, 2 or 3 amino acid residues) may be replaced by an alternative residue, for example a different naturally occurring amino acid or a different unnatural amino acid; or a different naturally occurring amino acid excluding methionine or a different unnatural amino acid. Preferably, an unnatural amino acid according to the present invention is one that is isosteric with a naturally occurring amino acid, for example norleucine. In one embodiment, an unnatural amino acid according to the present invention is one selected from norleucine, homoleucine and tert-butylalanine. For example, in one embodiment, one or more (for example each) methionine residues of the sequences described herein may be replaced by a different naturally occurring amino acid or unnatural amino acid, such as an amino acid selected from isoleucine, leucine, glutamine, norleucine, homoleucine and tert-butylalanine (for example isoleucine, leucine, glutamine, and norleucine; or norleucine, homoleucine and tert-butylalanine); and especially isoleucine and norleucine. For example, from 1 to 5 methionine residues, from 1 to 3 methionine residues (for example 1, 2 or 3 methionine residues), or 1 or 2 methionine residues, or 1 methionine residue, when present, may be replaced by a different naturally occurring amino acid or unnatural amino acid, such as an amino acid selected from isoleucine, leucine, glutamine, valine, norleucine, homoleucine and tert-butylalanine (for example isoleucine, leucine, glutamine, and norleucine; or norleucine, homoleucine and tert- butylalanine); and especially isoleucine and norleucine. Alternatively, or additionally, in certain embodiments, the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may contain amino acid substitutions wherein one or more residues is replaced by an unnatural amino acid. For example, in one embodiment, one or more residues of the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may be replaced by an unnatural amino acid, for example norleucine, homoleucine or tert-butylalanine. For example, from 1 to 15 residues may be replaced by unnatural amino acid(s), for example from 1 to 10 residues (for example 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 residues), from 1 to 5 residues (for example 1, 2, 3, 4 or 5), from 1 to 3 residues (for example 1, 2, or 3), or 1 residue may be replaced by unnatural amino acid(s) (for example norleucine, homoleucine or tert-butylalanine). For example, in one embodiment, one or more leucine residues of the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may be replaced by an unnatural amino acid, and preferably norleucine. For example, from 1 to 5 leucine residues, from 1 to 3 leucine residues (for example 1, 2 or 3 leucine residues), or 1 or 2 leucine residues, or 1 leucine residue, when present, may be replaced by unnatural amino acid (for example norleucine). For example, in certain embodiments, in the sequences described herein (for example, in the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein), and at a position at which a leucine residue is recited, the polypeptide has the sequence with the leucine residue independently substituted for an unnatural amino acid, and preferably norleucine. Alternatively, or additionally, in one embodiment, one or more methionine residues of the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may be replaced by an unnatural amino acid, for example norleucine, homoleucine or tert-butylalanine andpreferably norleucine. For example, from 1 to 5 methionine residues, from 1 to 3methionine residues (for example 1, 2 or 3 methionine residues), or 1 or 2 methionine residues, or 1 methionine residue, when present, may be replaced by unnatural amino acid (for example norleucine). For example, in certain embodiments, in the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described here), and at a position at which a methionine residue is recited, the polypeptide has the sequence with the methionine residue independently substituted for an unnatural amino acid for example norleucine, homoleucine or tert-butylalanine, and preferably norleucine. In certain embodiments, when present, one or more methionine residues of the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may be oxidised, for example in the form of methionine sulfoxide (“Met(O)”). For example, from 1 to 5 methionine residues, from 1 to 3 methionine residues (for example 1, 2 or 3 methionine residues), or 1 or 2 methionine residues, or 1 methionine residue, when present, may be oxidised (for example may be Met(O)). Alternatively, or additionally, in certain embodiments, the sequences described herein (for example, the CD16a- binding polypeptide and CD16a-binding oligomer sequences described herein) comprise a peptide purification tag or moiety (for example a histidine-tag (forexample a polyhistidine tag optionally comprising tyrosine), a biotin tag or amethionine-tag (for example a single methionine tag or a polymethionine tag)), a signalling tag or moiety (for example a glycine residue, or a signal peptide, for example selected from signal peptides OmpA, DsbA, PhoA, and PelB), a fluorophoretag (for example Alexa448 (AlexaFluorTM488) or Alexa647 (AlexaFluor TM647) a tag ormoiety to assist conjugation (a cysteine tag (for example a single cysteine at the C- orN- terminal)) or a tag to assist in detection in biological samples (for example an alfa,flag or myc-tag). Such tags and / or moieties may preferably be present at the N- terminal and / or the C-terminal of the CD16a-binding polypeptide and CD16a-bindingoligomer sequences described herein. In an embodiment, the CD16a-bindingpolypeptides and CD16a-binding oligomers described herein may comprise one ormore of the following: a peptide purification tag or moiety (for example a histidine-tag (for example a polyhistidine tag optionally comprising tyrosine) or a biotin tag; afluorophore tag (for example Alexa448 (AlexaFluorTM488) or Alexa647 (AlexaFluorTM647)); and a tag to assist in detection in biological samples (for example an alfa tag). Such tags and / or moieties may preferably be present at the N-terminal and / or the C-terminal of the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein. In an embodiment, a CD16a-binding polypeptide having such a tag and / or moiety attached is a polypeptide set out in Table 1 below: Example Label + Binder Sequence Compound Attachment + point Attachment pointQ4 AlexahBCMA, VDNKFNKENQFADEEIAALPNLNFYQKWAFIR Fluor™ 647hBCMA, hCD16a KLMDDPSQSANLLAEAKKLNDAQAPKGGGS GGGGSGVDNKFNKENQFADEEIAALPNLNFY COOH N-terminal QKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRRL PNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLN DAQAPK (SEQ ID NO: 5)Q5 EZ-Link™hBCMA, VDNKFNKENQFADEEIAALPNLNFYQKWAFIR Sulfo-NHS- hBCMA, hCD16a KLMDDPSQSANLLAEAKKLNDAQAPKGGGS Biotin GGGGSGVDNKFNKENQFADEEIAALPNLNFY N-terminal QKWAFIRKLMDDPSQSANLLAEAKKLNDAQA COOH PKGGGSGGGGSGVDNKFNKEQQIAQYEIRRL PNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLN DAQAPK (SEQ ID NO: 5) Table 1: Tagged and labelled versions of a CD16a-binding polypeptide of the invention In an embodiment, a CD16a-binding polypeptide comprising such a tag and / or moiety is a polypeptide comprising a sequence set out in Table 2 below:Example CD16a binder Sequence Compound / SEQ ID NO:SEQ ID Q3SEQ ID NO: 3 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPKGGGSGGGGSGV SEQ ID NO: 9 DNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMD DPSQSANLLAEAKKLNDAQAPKGGGSGGGGSGVD NKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDP SQSANLLAEAKKLNDAQAPKYYLEHHHHHH Q6SEQ ID NO: 2 GSSHHHHHHYYLEVDNKFNKENQFADEEIAALPNLSEQ ID NO:NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA 10 PKGGGSGGGGSGVDNKFNKENQFADEEIAALPNL NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNL NHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAP KGGGSGPSRLEEELRRRLTE Q7SEQ ID NO: 3 GSSHHHHHHYYLEVDNKFNKENQFADEEIAALPNLSEQ ID NO:NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA 11 PKGGGSGGGGSGVDNKFNKENQFADEEIAALPNL NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNL NHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAP KGGGSGPSRLEEELRRRLTE Table 2: Further tagged polypeptides of CD16a-binding polypeptides of the invention The inventors have found that the biological activity of CD16a-binding polypeptides of the present invention comprising one or more tags and / or moieties as describedabove is advantageously maintained in an in vitro model.Therefore, the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may further comprise an additional sequence of at least 1 histidine residue (and optionally at least 1 tyrosine residue) and / or at least 1 methionine residue; for example at least 4, at least 5, or at least 6 histidine residues (and optionally at least 1 tyrosine residue, for example 1, 2 or 3 tyrosine residues) and / or at least 1 methionine residue. In one embodiment, the sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may further comprise an additional sequence of at least 6 histidine residues and optionally at least 1 tyrosine residue (for example 6 histidine residues (e.g. HHHHHH) or 6 histidine residues and two tyrosine residues (e.g. YYHHHHHH)) and / or at least 1 methionine residue (for example 1 or 2 methionine residues). A peptide purification tag or moiety, for example a histidine-tag or a methionine-tag as described above, may preferably be present at the N-terminal and / or the C-terminal of the CD16a- binding polypeptide and CD16a-binding oligomer sequences described herein. For example, an additional sequence of at least 6 histidine residues (for example 6 histidine residues; or 6 histidine residues and two tyrosine residues) and / or at least 1 methionine residue (for example 1 or 2 methionine residues) may be present at the N-terminal and / or the C-terminal of the CD16a-binding polypeptide and CD16a- binding oligomer sequences described herein. The sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may further comprise an additional sequence of at least one cysteine (for example one cysteine) at the N- terminal or the C-terminal. The sequences described herein (for example, the CD16a- binding polypeptide and CD16a-binding oligomer sequences described here) mayfurther comprise a fluorophore tag (for example a Alexa448™ tag) at the N-terminalor the C-terminal. The sequences described herein (for example, the CD16a-bindingpolypeptide and CD16a-binding oligomer sequences described herein) may further comprise a signal peptide, for example selected from OmpA, DsbA, PhoA, and PelB, at the the N-terminal or the C-terminal, preferably the N-terminal. The sequences described herein (for example, the CD16a-binding polypeptide and CD16a-binding oligomer sequences described herein) may further comprise an additional sequence of at least one glycine (for example one glycine) at the N-terminal or the C-terminal. In certain embodiments, the CD16a-binding polypeptide is one in which the CD16a binding efficacy is at least 1%, at least 5%, or preferably at least 10% (morepreferably at least 15%, 20%, 25% or 50%) of SEQ ID NO: 2 or 3. When a CD16a-binding polypeptide is described herein as having CD16a binding efficacy that is atleast X% of a specific peptide (e.g. SEQ ID NO: 2 or 3), it is understood that the IC50concentration of the polypeptide for binding to the CD16a receptor is no more than 100 / X times the IC50 concentration for the specific peptide (SEQ ID NO: 2 or 3) to the CD16a receptor, when measured under the same conditions. For example, if the binding efficacy of a CD16a-binding polypeptide is at least 5%, and more preferably at least 10%, 20%, 25% or 50% of the CD16a binding efficacy of the specific peptide (e.g. SEQ ID NO: 2 or 3), that is to say that the IC50 concentration of the alternative polypeptide for binding to the CD16a receptor is no more than 20 times and more preferably 10 times, 5 times, 4 times or 2 times, respectively, the IC50 concentration for the specific peptide (e.g. SEQ ID NO: 2 or 3) to the CD16a receptor, when measured under the same conditions. In certain embodiments, alternatively, or additionally, the CD16a-binding polypeptide is one that competes with SEQ ID NO: 2 or 3. The CD16a-binding polypeptides of the present invention have binding affinity for the CD16a receptor; and may optionally have binding affinity for the CD16b receptor. For example, in certain embodiments the CD16a-binding polypeptides of the present invention have similar binding affinity for the CD16a receptor and CD16b receptor; in certain embodiments, the CD16a-binding polypeptides of the present invention have stronger binding affinity for the CD16a receptor than the CD16b receptor and in certain embodiments, the CD16a-binding polypeptides of the present invention have stronger binding affinity for the CD16b receptor than the CD16a receptor. The CD16a-binding polypeptides of the present invention may have binding affinityto one or both genotypic variations of the CD16a (FcγRIIIa) receptor: the FcγRIIIa-176V / F polymorphism (rs396991) (in some publications where the leader sequence is excluded, position 176 is reported as position 158 and this numbering is also used in the Examples herein). Preferably, the CD16a-binding polypeptides of the presentinvention have binding affinity for both genotypic variations of the CD16a (FcγRIIIa)receptor. In certain embodiments, the CD16a-binding polypeptides of the presentinvention have a stronger binding affinity for the valine (V) position 176 phenotype, or have a stronger binding affinity for the phenylalanine (F) position 176 phenotype, or have similar binding at both the F and the V position 176 phenotype. The present invention provides a CD16a-binding polypeptide which comprises at least one motif that binds to CD16a, wherein said polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]. In one embodiment, Helix 1 comprises the sequence X9X10X11AX13X14EIX17X18 and Helix 2 comprises the sequence X24X25QX27X28AFX31X32X33LX35, wherein, X9 is Q; X10 is Q; X11 is I; X13 is Q; X14 is Y; X17 is R; X18 is R; X24 is H; X25 is H;X27 is T; X28 is F; X31 is I; X32 is K; X33 is S; and X35 is L. In such embodiments, the N-terminus of Helix 1 may further comprise the sequenceX6X7X8; wherein the sequence is preferably NKE (i.e. X6 is N; X7 is K; X8 is E).Alternatively, or additionally, in such embodiments, the C-terminus of Helix 2 mayfurther comprise the sequence X36X37; wherein the sequence is, preferably, DD i.e.X36is D; and X37is D). In preferred embodiments, the motif sequence additionally has the residues NKE at positions X6X7X8(i.e. X6is N; X7is K; X8is E). In preferred embodiments, the motif sequence additionally has the residues DD at its positions X36X37(i.e. X36is D; and X37is D). For example, the motif sequences have NKE at positions X6X7X8and DD at positions X36X37(i.e. X6is N; X7is K; X8is E; X36is D; and X37is D). Therefore, in preferred embodiments, the motif sequence may be selected from: NKEX9X10X11AX13X14EIX17X18X19X20X21X22X23X24X25QX27X28AFX31X32X33LX35X36X37; X6X7X8X9X10X11AX13X14EIX17X18X19X20X21X22X23X24X25QX27X28AFX31X32X33LX35DD; and NKEX9X10X11AX13X14EIX17X18X19X20X21X22X23X24X25QX27X28AFX31X32X33LX35DD; wherein X9is Q; X10is Q; X11is I; X13is Q; X14is Y; X17is R; X18is R; X24is H; X25is H; X27is T; X28is F; X31is I; X32is K; X33is S; and X35is L. In one embodiment the CD16a binding motif, being the portion [Helix 1]-[Separating portion]-[Helix 2], is (i.e. has a sequence): X6X7X8X9X10X11AX13X14EIX17X18X19 X20X21X22X23X24X25QX27X28AFX31X32 X33LX35X36X37 Wherein X9 is Q; X10 is Q; X11 is I; X13 is Q; X14 is Y; X17 is R; X18 is R; X24 is H; X25 is H; X27 is T; X28 is F; X31 is I; X32 is K; X33 is S; and X35 is L; and X6 is N; X7 is K; X8 is E; X19 is L; X20 is P; X21 is N; X22 is L; X23 is N; and X36 is D; and X37 is D. More preferably, in embodiments of the present invention: Helix 1 comprises the sequence X6X7X8X9X10X11AX13X14EIX17X18X19 and / or Helix 2 comprises the sequence X23X24X25QX27X28AFX31X32X33LX35X36X37, wherein, X9is Q; X10is Q; X11is I; X13is Q; X14is Y; X17is R; X18is R; X24is H; X25is H; X27is T; X28is F; X31is I; X32is K; X33is S; and X35is L; and X6is D, E, N or Q (more preferably N) or is absent (for example X6is D, E, N or Q, andmore preferably N); X7 is H, K or R (preferably K) or is absent (for example X7 is H, K orR; and more preferably K); X8 is D, E, N or Q (preferably E) or is absent (for exampleX8 is D, E, N or Q; and more preferably E); X19 is G, A, V, L or I (preferably L) or isabsent (for example X19is G, A, V, L or I; and more preferably L); X23is D, E, N or Q (preferably N) or is absent (for example X23is D, E, N or Q; and more preferably N);X36 is D, E, N or Q (more preferably D) or is absent (for example X36 is D, E, N or Q; andmore preferably D); and X37 is D, E, N or Q (preferably D) or is absent (for example X37is D, E, N or Q; and more preferably D). In another embodiment, X9is Q; X10is Q; X11is I; X13is Q; X14is Y; X17is R; X18is R; X24is H; X25is H; X27is T; X28is F; X31is I; X32is K; X33is S; and X35is L; and X6may be any naturally occurring amino acid or is absent; X7may be any naturally occurring amino acid or is absent; X8 may be any naturally occurring amino acid or is absent; X19may be any naturally occurring amino acid or is absent; X23may be any naturally occurring amino acid or is absent; X36 may be any naturally occurring amino acid or is absent; and X37 may be any naturally occurring amino or is absent. More preferably, X6may be any naturally occurring amino acid; X7may be any naturally occurring amino acid; X8 may be any naturally occurring amino acid; X19 may be any naturally occurring amino acid; X23 may be any naturally occurring amino acid; X36 may be any naturally occurring amino acid; and X37 may be any naturally occurringamino acid.Preferably, X6 is N; X7 is K; X8 is E; X19 is L; X23 is N; X36 is D; and X37 is D. In one especially preferred embodiment, the CD16a-binding motif sequence comprises the sequence:QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1).In another especially preferred embodiment, the CD16a-binding motif sequenceconsists of the sequence:QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1).In one especially preferred embodiment, the CD16a-binding motif sequence is:QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1).In a polypeptide of the invention described herein, optionally from 1 to 5 residues (for example 1, 2, 3, 4 or 5), preferably 1, 2 or 3 residues, in the sequence are replaced by an alternative residue. Preferably, in embodiments wherein optionally from 1 to 5 residues (for example 1, 2, 3, 4 or 5), preferably 1, 2 or 3 residues, in the sequence are replaced by an alternative residue, the replacement residue is a conservative replacement. Preferably in a polypeptide of the invention described herein above or below, no residues in the sequence are replaced by an alternative residue.For example, in certain embodiments, the sequence is one of SEQ ID NO: 1, 2, 4, 5, 6or 7 as described herein, and optionally from 1 to 5 residues (for example 1, 2, 3, 4 or5, or 1, 2 or 3 residues), in the sequence are replaced by an alternative residue, wherein each replacement residue is a conservative replacement. Preferably, thesequence is one of SEQ ID NO: 1, 2, 4, 5, 6 or 7 as described herein, and no residuesin the sequence are replaced by an alternative residue. As mentioned above, in embodiments of the invention a number of residues may each be substituted by an alternative residue, as described herein. For example, in the embodiments described herein, even when not explicitly mentioned, optionally 1 to 5 (for example 1, 2, 3, 4 or 5), and preferably optionally 1 to 3 (for example 1, 2, or 3), residues in the sequence of Helix 1 and / or Helix 2 defined above are replaced by an alternative residue (for example replaced by an alternative residue that is a conservative replacement). In any such alternative polypeptides of the invention with alternative residues in place, binding to the CD16a receptor is maintained. For example, the CD16a binding efficacy is at least 1% of the binding efficacy of the peptide of SEQ ID NO: 2 or 3 (i.e. binding efficacy of the peptide of SEQ ID NO: 2 or 3 to the CD16a receptor, when measured under the same conditions (as described above)). Alternatively, or additionally, for example, in any such alternative polypeptides of the invention with alternative residues in place, the CD16a-binding polypeptide is one that competes with SEQ ID NO: 2 or 3. In certain preferred embodiments, the binding efficacy is at least 5%, and more preferably at least 10%, 20%, 25% or 50% of the binding efficacy of the peptide of SEQ ID NO: 2 or 3 (i.e. binding efficacy of the peptide of SEQ ID NO: 2 or 3 to the CD16a receptor, when measured under the same conditions). In certain embodiments of CD16a-binding polypeptides of the invention, Proline (P) and Cysteine (C) are not present in the CD16a binding motif of a CD16a binding polypeptide of the present invention. In certain embodiments Glycine (G) is also not present in the CD16a binding motif of a CD16a binding polypeptide of the present invention. The CD16a-binding polypeptide of the invention has the overall structure [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]. The separating portion may be a sequence of from 1 to 5 (for example 1, 2, 3, 4 or 5) naturally occurring amino acids. Preferably, the separating portion is a sequence of from 2 to 5 (for example 2, 3, 4 or 5) naturally occurring amino acids. For example, the separating portion is a sequence of from 3 to 5 (for example 3, 4 or 5) naturally occurring amino acids. Preferably the separating portion is a sequence of 3 amino acids. In certain embodiments, the separating portion has the sequence X20X21X22, wherein X20 is any naturally occurring amino acid, X21 is any naturally occurring amino acid; and X22 is any naturally occurring amino acid; and wherein optionally one or two of X20, X21 or X22 are absent. For example, none of X20, X21 or X22 is absent, one of X20, X21 or X22 is absent, or two of X20, X21 or X22 are absent. More preferably, none of X20, X21 or X22 is absent or one of X20, X21 or X22 is absent. Most preferably none of X20, X21 or X22is absent, i.e. the separating portion has the sequence X20X21X22, wherein X20is any naturally occurring amino acid, X21 is any naturally occurring amino acid; and X22 is any naturally occurring amino acid.Preferably, X20 is S, T, M, P, F, Y or W (for example P or T); X21 is D, E, N or Q; and X22 isG, A, V, L or I; wherein optionally one or two (for example one) of X20, X21or X22are absent.In preferred embodiments, X20 is S, T, M, P, F, Y or W (for example P or T), X21 is D, E,N or Q; and X22 is G, A, V, L or I. More preferably, X20 is P or T; X21 is N; and X22 is L. Forexample, the separating portion has the sequence PNL or TNL. Most preferably, the separating portion has the sequence PNL (i.e. X20is P, X21is N, and X22is L). The N-terminal portion may be absent or may be a sequence of 1 to 15 naturally occurring amino acids. For example, the N-terminal portion may be absent or may be a sequence of from 1 to 10, from 1 to 8, from 1 to 6, or from 1 to 5 naturally occurring amino acids, for example 1, 2, 3, 4 or 5 naturally occurring amino acids. In certain embodiments, the N-terminal portion has the sequence X1X2X3X4X5, wherein X1is any naturally occurring amino acid or is absent; X2is any naturally occurring amino acid or is absent; X3 is any naturally occurring amino acid or is absent; X4is any naturally occurring amino acid or is absent; and X5is any naturally occurring amino acid or is absent. Preferably, the N-terminal portion has the sequence X1X2X3X4X5, wherein X1 is G, A, V,L, I or is absent, X2 is D, E, N, Q or is absent, X3 is D, E, N, Q or is absent, X4 is H, K, R oris absent, and X5 is F, Y, W or is absent. More preferably, X1 is V, G or absent (for example V or absent); X2 is D or absent; X3 is N or absent; X4 is K or absent; and X5 is F or absent. In certain embodiments, preferably none of X1, X2, X3 ,X4 and X5 is absent; X1 is absentand the other residues are not absent; X1 and X2 are absent and the other residuesare not absent; X1, X2 and X3 are absent and the other residues are not absent; X1, X2,X3 and X4 are absent and the other residue is not absent; or all of X1, X2, X3 ,X4 and X5 are absent. In certain especially preferred embodiments, the N-terminal portion has the sequence X1X2X3X4X5wherein X1is V or G (preferably V), X2is D, X3is N, X4is K, and X5is F; X1 is absent, X2 is D, X3 is N, X4 is K, and X5 is F; X1 is absent, X2 is absent, X3 is N, X4 is K, and X5is F; X1is absent, X2is absent, X3is absent, X4is K, and X5is F; X1is absent, X2is absent, X3is absent, X4is absent, and X5is F; or X1is absent, X2is absent, X3is absent, X4is absent, and X5is absent. For example, X1is V or G (preferably V), X2is D, X3is N, X4is K, and X5is F; or X1is absent, X2is absent, X3is absent, X4is absent, and X5is absent, i.e. the N-terminal portion has the sequence VDNKF, GDNKF or is absent; and more preferably has the sequence VDNKF or is absent. In one preferred embodiment, X1is V or G (preferably V), X2is D, X3is N, X4is K, and X5is F, i.e. the N-terminal portion has the sequence VDNKF or GDNKF; and more preferably the N-terminal portion has the sequence VDNKF. The C-terminal portion may be absent or may be a sequence of 1 to 50 naturally occurring amino acids. For example, the C-terminal portion may be absent or may be a sequence of from 1 to 40, 1 to 35, 1 to 30, from 1 to 25, from 1 to 22, or from 1 to 21 naturally occurring amino acids. Preferably, the C-terminal portion may be absent or may be a sequence of from 10 to 35, 10 to 30, from 15 to 25, from 18 to 22, from 1 to 21 naturally occurring amino acids, for example 18, 19, 20, 21 or 22 naturally occurring amino acids. Preferably, the C-terminal portion has a sequence such that it enhances target binding by the CD16a-binding motif of Helix 1 and Helix 2. In certain embodiments, the C-terminal portion is absent or has the sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38is a sequence of 1 to 14 naturally occurring amino acids, X39 is any naturally occurring amino acid, X56 is any naturally occurring amino acid or is absent, X57 is any naturally occurring amino acid or is absent, and X58 is any naturally occurring amino acid or is absent, and optionally wherein from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservative replacement.Preferably no residues are replaced by an alternative residue.In certain embodiments, X38 is a sequence of 1 to 9, 1 to 7 or 1 to 5 naturally occurring amino acids. More preferably X38is a sequence of 1 to 4, for example 1, 2, 3 or 4 amino acids. In one especially preferred embodiment, X38 is any naturally occurring amino acid (i.e. any single (one) naturally occurring amino acid residue). In one preferred embodiment, the C-terminal portion has the sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38is P, X39is S, T, M, P, F, Y or W, X56isG, A, V, L, I or is absent, X57 is P or is absent, and X58 is H, K, R or is absent, andoptionally wherein from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservativereplacement. Preferably no residues are replaced by an alternative residue. Inanother preferred embodiment, the C-terminal portion has the sequencePSQSANLLAEAKKLNDAQX56X57X58, wherein X56 is G, A, V, L, I or is absent, X57 is P or isabsent, and X58 is H, K, R or is absent, and optionally wherein from 1 to 5 (forexample 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservative replacement. In an especially preferred embodiment, the C-terminal portion has the sequenceX38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38is P, X39 is S, X56 is A or is absent, X57is P or is absent, and X58 is K or is absent, and optionally wherein from 1 to 5 (forexample 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replacedby an alternative residue that is a conservative replacement . Preferably no residuesare replaced by an alternative residue. In another especially preferred embodiment,the C-terminal portion has the sequence PSQSANLLAEAKKLNDAQX56X57X58, whereinX56 is A or is absent, X57 is P or is absent, and X58 is K or is absent, and optionallywherein from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservative replacement. For example, in certain embodiments the C-terminal portion has the sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38 is P, and X39 is S; and:X56 is A, X57 is P, and X58 is K; or X56 is A, X57 is P, and X58 is absent; or X56 is A, X57 isabsent, and X58 is absent; or X56 is absent, X57 is absent, and X58 is absent. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservativereplacement. Preferably no residues are replaced by an alternative residue. Or, forexample, the C-terminal portion has the sequence PSQSANLLAEAKKLNDAQX56X57X58, wherein X56is A, X57is P, and X58is K; or X56is A, X57is P, and X58is absent; or X56is A, X57is absent, and X58is absent; or X56is absent, X57is absent, and X58is absent. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is aconservative replacement. Preferably no residues are replaced by an alternativeresidue. In one preferred embodiment, the C-terminal portion has the sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38is P, and X39is S; and X56is A, X57isP, and X58 is K. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residuethat is a conservative replacement. Preferably no residues are replaced by analternative residue. Or, for example, the C-terminal portion has the sequencePSQSANLLAEAKKLNDAQX56X57X58, wherein X56 is A, X57 is P, and X58 is K. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is aconservative replacement. Preferably no residues are replaced by an alternativeresidue. In an alternative preferred embodiment the C-terminal portion has the sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38is P, and X39 is S; and: X56 is absent, X57 is absent, and X58 is absent. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replacedby an alternative residue that is a conservative replacement. Preferably no residuesare replaced by an alternative residue. Or, for example, the C-terminal portion hasthe sequence PSQSANLLAEAKKLNDAQX56X57X58, X56 is absent, X57 is absent, and X58 is absent. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residuethat is a conservative replacement. Preferably no residues are replaced by analternative residue. In one embodiment, the N-terminal portion has the sequence X1X2X3X4X5wherein X1is V or G (preferably V), X2is D, X3is N, X4is K, and X5is F; X1is absent, X2is D, X3is N, X4is K, and X5is F; X1is absent, X2is absent, X3is N, X4is K, and X5is F; X1is absent, X2is absent, X3is absent, X4is K, and X5is F; X1is absent, X2is absent, X3is absent, X4is absent, and X5is F; or X1is absent, X2is absent, X3is absent, X4is absent, and X5is absent (for example, X1is V or G (preferably V), X2is D, X3is N, X4is K, and X5is F, or X1is absent, X2is absent, X3is absent, X4is absent, and X5is absent); and the C-terminal portion has the sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38is P, X39isS, T, M, P, F, Y or W, X56 is G, A, V, L, I or is absent, X57 is P, and X58 is H, K, or R, andoptionally wherein from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservative replacement; and more preferably X38 is P, X39 is S, X56 is A, X57 is P, and X58 is K, and optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservative replacement.Preferably no residues are replaced by an alternative residue.In another embodiment, the N-terminal portion has the sequence X1X2X3X4X5 wherein X1 is V or G (preferably V), X2 is D, X3 is N, X4 is K, and X5 is F; X1 is absent, X2 is D, X3 is N, X4 is K, and X5 is F; X1 is absent, X2 is absent, X3 is N, X4 is K, and X5 is F; X1 is absent, X2 is absent, X3 is absent, X4 is K, and X5 is F; X1 is absent, X2 is absent, X3 is absent, X4 is absent, and X5 is F; or X1 is absent, X2 is absent, X3 is absent, X4 is absent, and X5is absent (for example, X1is V or G (preferably V), X2is D, X3is N, X4is K, and X5is F, or X1 is absent, X2 is absent, X3 is absent, X4 is absent, and X5 is absent); and the C- terminal portion has the sequence PSQSANLLAEAKKLNDAQX56X57X58, wherein X56isG, A, V, L, I or is absent, X57 is P, and X58 is H, K, or R, and optionally wherein from 1 to5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replacedby an alternative residue that is a conservative replacement; and more preferably X56is A, X57is P, and X58is K, and optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residuethat is a conservative replacement. Preferably no residues are replaced by analternative residue. In one very preferred embodiment, X1is V or G (preferably V), X2is D, X3is N, X4is K,and X5 is F; and X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is H, K, or R(preferably K). In an alternative very preferred embodiment X1is absent, X2is absent, X3is absent, X4is absent, and X5 is absent; and X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is H,K, or R (preferably K). In another preferred embodiment, the N-terminal portion has the sequence X1X2X3X4X5, wherein X1is G, A, V, L, or I, X2is D, E, N, or Q, X3is D, E, N, or Q, X4is H, K,or R, and X5 is F, Y, or W (for example, X1 is V or G (preferably V), X2 is D, X3 is N, X4 isK, and X5 is F); and the C-terminal portion has sequence X38X39QSANLLAEAKKLNDAQX56X57X58, wherein X38 is P, X39 is S, T, M, P, F, Y or W(preferably S); and X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is H, K, or R(preferably K); X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is absent; X56 is G, A,V, L or I (preferably A), X57 is absent, and X58 is absent; or X56 is absent, X57 is absent,and X58 is absent. More preferably, X56 is G, A, V, L or I (preferably A), X57 is P, and X58is H, K, or R (preferably K); or X56 is absent, X57 is absent, and X58 is absent. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence QSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is a conservativereplacement. Preferably no residues are replaced by an alternative residue.In one preferred embodiment, the N-terminal portion has the sequence X1X2X3X4X5, wherein X1is G, A, V, L, or I, X2is D, E, N, or Q, X3is D, E, N, or Q, X4is H, K, or R, and X5is F, Y, or W (for example, X1 is V or G (preferably V), X2 is D, X3 is N, X4 is K, and X5 isF); and the C-terminal portion has sequence PSQSANLLAEAKKLNDAQX56X57X58,wherein X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is H, K, or R (preferably K);X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is absent; X56 is G, A, V, L or I(preferably A), X57is absent, and X58is absent; or X56is absent, X57is absent, and X58is absent. More preferably, X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is H, K,or R (preferably K); or X56is absent, X57is absent, and X58is absent. In such embodiments optionally from 1 to 5 (for example 1, 2, 3, 4 or 5; preferably 1, 2 or 3) of the residues in the sequence PSQSANLLAEAKKLNDAQ are replaced by an alternative residue, for example replaced by an alternative residue that is aconservative replacement. Preferably no residues are replaced by an alternativeresidue. In one very preferred embodiment, X1 is V or G (preferably V), X2 is D, X3 is N, X4 is K, and X5is F; and X56is absent, X57is absent, and X58is absent. In an alternative very preferred embodiment, X1is V or G (preferably V), X2is D, X3isN, X4 is K, and X5 is F; X56 is G, A, V, L or I (preferably A), X57 is P, and X58 is H, K, or R(preferably K). In certain embodiments, (i) the separating portion has the sequence X20X21X22; and / or the N-terminal portion has the sequence X1X2X3X4X5 ; and / or the C-terminal portion has the sequence PSQSANLLAEAKKLNDAQX56X57X58; wherein, in said separating portion, X20 is P or T; X21 is N; X22 is L; wherein in said N-terminal portion, X1 is V or G (preferably V), or absent; X2 is D or absent; X3is N or absent; X4is K or absent; X5is F or absent; and wherein in said C-terminal portion, X56is A or absent; X57is P or absent; X58is K or absent. Alternatively, (ii) the separating portion, N-terminal portion, and C-terminal portion are as defined in (i) above, wherein optionally (a) within each portion 1, 2 or 3 residues are replaced by an alternative residue; or (b) within those portions taken together at least 1 and no more than 5 (for example, 1, 2, 3, 4, or 5) residues are replaced by an alternative residue. In such embodiments, preferably the separating portion has the sequence PNL or TNL (more preferably PNL). Alternatively, or additionally, in such embodiments, the N-terminal portion has the sequence VDNKF. In one embodiment, the N-terminal portion may comprise the sequence X1X2X3X4X5, wherein: X1is V, or absent; X2is D or absent; X3is N or absent; X4is K or absent; X5is F or absent. For example, the N-terminal portion may comprise the sequence VDNKF. The separating portion may comprise the sequence X20X21X22, wherein: X20is P or T; X21is N; X22is L. For example, the separating portion may comprise the sequence PNL. The C-terminal portion may comprise the sequence PSQSANLLAEAKKLNDAQX56X57X58, wherein: X56 is A or absent; X57 is P or absent; X58 is K or absent. For example, the C-terminal portion may comprise the sequence PSQSANLLAEAKKLNDAQAPK or PSQSANLLAEAKKLNDAQ (preferably PSQSANLLAEAKKLNDAQAPK). The C-terminal portion may have the structure [Second separating portion]-[Helix 3]-[C-terminal sequence]. For example: -the Second separating portion comprises the sequence PS;- the Helix 3 portion comprises the sequence QSANLLAEAKKLNDAQ;- and the C-terminal sequence comprises the sequence APK or is absent.In certain embodiments, within those five portions (N-terminal portion, separating portion, second separating portion, Helix 3, and C-terminal sequence) taken together, at least 1 and no more than 8 (for example 5) of the residues may be replaced by an alternative residue. For example, the number of replaced residues is at least 1 and no more than 7, at least 1 and no more than 6, at least 1 and no more than 5, at least 1 and no more than 4, for example at least 1 and no more than 3, for example at least 1 and no more than 2. Particularly, there may be 1, 2, 3, 4 or 5 replacement residues in total in those portions. In preferred embodiments, within those five portions (N-terminal portion, separating portion, second separating portion, Helix 3, and C-terminal sequence) taken together, no residues are replaced by an alternative residue Thus, certain embodiments, across the entire CD16a-binding polypeptide of the invention (i.e. across the entire overall structure [N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]), at least 1 and no more than 11 of the residues may be replaced by an alternative residue. For example, the number of replaced residues is at least 1 and no more than 10, for example at least 1 and no more than 9, for example at least 1 and no more than 8, for example at least 1 and no more than 7, for example at least 1 and no more than 6. Particularly, there maybe 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 replacement residues in total across the entireoverall structure [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C- terminal portion]. In preferred embodiments, across the entire CD16a-binding polypeptide of the invention (i.e. across the entire overall structure [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]), no residues are replaced by an alternative residue.In advantageous embodiments of CD16a -binding polypeptides of the invention,where the C-terminal portion comprises a helical or substantially helical region (for example Helix 3 as described immediately above; for example the sequence QSANLLAEAKKLNDAQ), Proline (P) and Cysteine (C) are not present in that helical or substantially helical region. In another embodiment, additionally Glycine (G) is also not present in that helical or substantially helical region (for example Helix 3 as described immediately above; for example the sequence QSANLLAEAKKLNDAQ). In one very preferred embodiment of the invention, the CD16a binding polypeptide comprises the sequence VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2). In such a sequence, optionally from 1 to 5 (for example optionally 1, 2 or 3) residues in the sequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement. Preferably, in such a sequence, no residues in the sequence are replaced by an alternative residue. In one very preferred embodiment of the invention, the CD16a binding polypeptideconsists of the sequenceVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2). In one very preferred embodiment of the invention, the sequence of the CD16a- binding polypeptide is: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2).Also described herein, the CD16a binding polypeptide may comprise (or consist of)the sequence VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3). In such a sequence, optionally from 1 to 5 (for example optionally 1, 2 or 3) residues in the sequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement. Preferably, in such a sequence, no residues in the sequence are replaced by an alternative residue.The CD16a binding polypeptide may comprise (or consist of) the sequenceVDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3)in embodiments wherein the CD16a-binding polypeptide comprises the followingstructure: [BCMA-binding polypeptide]-[Linker 1]-[BCMA-binding polypeptide]-[Linker 2]-[CD16a-binding polypeptide] wherein: each of the BCMA-binding polypeptides comprises (or consists of) the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide comprises (or consists of) the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2)or comprises (or consists of) the sequence:VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 has the sequence (GGGSG)n, where n is 1, 2 or 3. In such embodiments, optionally from 1 to 5 (for example optionally 1, 2 or 3)residues in one, two or each sequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement. Preferably, in such aembodiments, no residues in each sequence are replaced by an alternative residue.For example, in such an embodiment, each of the BCMA-binding polypeptides consists of the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide consists of the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or consists of the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 consists of the sequence (GGGSG)n, where n is 1, 2 or 3.The invention further provides a CD16a-binding polypeptide, wherein the CD16a-binding polypeptide consists of one motif that binds to CD16a, wherein saidpolypeptide consists of the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2], wherein the CD16a-binding motif sequence is: QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1), and optionally the peptide further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions.The invention further provides a CD16a-binding polypeptide of the invention,wherein the CD16a-binding polypeptide consists of the CD16a-binding polypeptideand wherein the sequence of the CD16a-binding polypeptide is: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2), and optionally further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions.In one very preferred embodiment the CD16a-binding polypeptide (for example aCD16a-binding polypeptide of the invention described above or below) consists ofone motif that binds to CD16a, wherein said polypeptide consists of the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2] wherein the CD16a-binding motif sequence is QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1) and optionally further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions.In one very preferred embodiment the CD16a-binding polypeptide consists of aCD16a-binding polypeptide of the invention and wherein the sequence of the CD16a-binding polypeptide is VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) and optionally further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions.The invention further provides a CD16a-binding polypeptide, wherein the CD16a-binding polypeptide consists of one motif that binds to CD16a, wherein saidpolypeptide consists of the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2], and the peptide further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions); and wherein the CD16a-binding polypeptide and an additional functional portion are separated by a linker as described herein.The invention further provides a CD16a-binding polypeptide of the invention,wherein the CD16a-binding polypeptide consists of the CD16a-binding polypeptidefurther comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions); and wherein the CD16a-binding polypeptide and an additional functional portion are separated by a linker as described herein.In one very preferred embodiment the CD16a-binding polypeptide of the inventiondescribed above or below consists of one motif that binds to CD16a, wherein said polypeptide consists of the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2], and the peptide further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions; and wherein the CD16a-binding polypeptide and an additional functional portion are separated by a linker as described herein.In one very preferred embodiment the CD16a-binding polypeptide consists of aCD16a-binding polypeptide of the invention and further comprises one or moreadditional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions; and wherein the CD16a-binding polypeptide and an additional functional portion are separated by a linker as described herein.For the avoidance of doubt, in embodiments in which a CD16a-binding polypeptideconsists of a CD16a-binding motif and / or a CD16a-binding polypeptide, the CD16a- binding polypeptide is not connected to a further CD16a-binding polypeptide, i.e. the CD16a-binding polypeptide is not a portion of a CD16a-binding oligomer.In another very preferred embodiment the CD16a-binding polypeptide of theinvention described above or below consists of one motif that binds to CD16a, wherein said polypeptide consists of the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2], and wherein the polypeptide further comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example one, two or three additional functional portions. In another very preferred embodimentthe CD16a-binding consists of a CD16a-binding polypeptide of the invention, andfurther comprises one or more additional functional portions as described below (for example 1, 2, 3, 4, 5, 6 or more); for example 1, 2 or 3 additional functional portions (preferably 1 or 2 additional functional portions); and wherein the CD16a-binding polypeptide and an additional functional portion are separated by a linker as described herein. Multimeric CD16a-binding polypeptides: CD16a-binding oligomers In certain aspects, the present invention provides a CD16a-binding oligomer which comprises at least two (i.e. two or more than two, for example 2, 3, 4, 5, 6 or more; preferably 2, 3 or 4) CD16a-binding polypeptides of the present invention, wherein the CD16a-binding polypeptides of a CD16a-binding oligomers of the invention areconnected via one or more linkers of the present invention as described herein. Inone embodiment, the CD16a-binding oligomer of the present invention comprises two CD16a-binding polypeptides of the present invention. In another embodiment, a CD16a-binding oligomer of the present invention comprises at least three, at least four, at least 5 or at least 6 CD16a-binding polypeptides of the present invention, for example 3, 4, 5 or 6 or more CD16a-binding polypeptides of the present invention. The CD16a-binding polypeptides of a CD16a-binding oligomers of the invention may optionally be connected via one or more linkers, for example one or more linkers as described herein. For the avoidance of doubt, the term “separated by a linker” as used herein means connected by or connected via a linker. A CD16a-binding oligomer of the present invention is a multimeric binder, as it has multiple CD16a binding motifs, i.e. it has a CD16a binding motif ([Helix 1]-[Separating portion]-[Helix 2]) in each CD16a-binding polypeptide it comprises. A CD16a-binding oligomer of the present invention comprises, at least, a first CD16a- binding polypeptide which is a CD16a-binding polypeptide of the present invention, and a second CD16a-binding polypeptide which is a CD16a-binding polypeptide of the present invention. The first and second CD16a-binding polypeptides may have the same sequence. Alternatively, the first and second CD16a-binding polypeptides may have different sequences. A CD16a-binding oligomer of the present invention may optionally further comprise a third CD16a-binding polypeptide which is a CD16a-binding polypeptide of the present invention. The third CD16a-binding polypeptides may have the same sequence as the first and / or second CD16a-binding polypeptides sequences. Alternatively, the third CD16a-binding polypeptides may have a different sequence to the first and second CD16a-binding polypeptide. A CD16a-binding oligomer of the present invention may optionally further comprise a fourth CD16a-binding polypeptide which is a CD16a-binding polypeptide of thepresent invention. The fourth CD16a-binding polypeptides may have the samesequence as the first and / or second and / or third CD16a-binding polypeptides sequences. Alternatively, the fourth CD16a-binding polypeptide may have a different sequence to the first, second and third CD16a-binding polypeptides. In one embodiment, a CD16a-binding oligomer of the present invention comprises afirst CD16a-binding polypeptide that comprises a first binding motif comprising orconsisting of SEQ ID NO: 1 (and wherein optionally from 1 to 5 (preferably 1, 2 or 3) residues in the sequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement); and a second CD16a-binding polypeptide that comprises a second binding motif comprising or consisting of SEQID NO: 1 (and wherein optionally from 1 to 5 (preferably 1, 2 or 3) residues in thesequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement). The first and second CD16a-binding motifs may have thesame sequence or a different sequence. In another embodiment, a CD16a-bindingoligomer of the present invention comprises a first CD16a-binding polypeptide thathas a sequence selected from SEQ ID NOs. 2 and 3 (and wherein optionally from 1 to5 (preferably 1, 2 or 3) residues in the sequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement); and a second CD16a-binding polypeptide that has sequence selected from SEQ ID NOs.2 and 3 (and wherein optionally from 1 to 5 (preferably 1, 2 or 3) residues in the sequence are replaced by an alternative residue, and preferably a residue that is a conservative replacement). The first and second CD16a-binding polypeptide may have the same sequence or a different sequence. For the avoidance of doubt, when used herein “[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]” means that the CD16a binding polypeptide sequence is N-terminus to C-terminus, left to right; and when used herein “[C-terminal portion]-[Helix 2]-[Separating portion]-[Helix 1]-[N-terminal portion]” means that the CD16a binding polypeptide sequence is C-terminus to N- terminus, left to right. For the avoidance of doubt, when used herein “ -[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]” (i.e. with the “-“ prefix added)this indicates that the point of attachment is on the N-terminal portion of the CD16abinding polypeptide (as well as that the CD16a binding polypeptide sequence is N- terminus to C-terminus, left to right). When used herein “ -[C-terminal portion]- [Helix 2]-[Separating portion]-[Helix 1]-[N-terminal portion]” (i.e. with the “ prefixadded) this indicates that the point of attachment is on the C-terminal portion of theCD16a binding polypeptide (as well as that the CD16a binding polypeptide sequence is C-terminus to N-terminus, left to right). For the avoidance of doubt, when used herein “[hBCMA N-terminal portion]-[hBCMA Helix 1]-[hBCMA Separating portion]-[hBCMA Helix 2]-[hBCMA C-terminal portion]” means that the hBCMA binding polypeptide sequence is N-terminus to C-terminus, left to right; and when used herein “[hBCMA C-terminal portion]-[hBCMA Helix 2]- [hBCMA Separating portion]-[hBCMA Helix 1]-[hBCMA N-terminal portion]” means that the hBCMA binding polypeptide sequence is C-terminus to N-terminus, left to right. For the avoidance of doubt, when used herein “ -[hBCMA N-terminal portion]- [hBCMA Helix 1]-[hBCMA Separating portion]-[hBCMA Helix 2]-[hBCMA C-terminalportion]” (i.e. with the “-“ prefix added) indicates that the point of attachment is onthe N-terminal portion of the hBCMA binding polypeptide (as well as that the hBCMA binding polypeptide sequence is N-terminus to C-terminus, left to right). When used herein “ -[hBCMA C-terminal portion]-[hBCMA Helix 2]-[hBCMA Separating portion]- [hBCMA Helix 1]-[hBCMA N-terminal portion]” (i.e. with the prefix added) thisindicates that the point of attachment is on the C-terminal portion of the hBCMAbinding polypeptide (as well as that the hBCMA binding polypeptide sequence is C- terminus to N-terminus, left to right).The CD16a-binding polypeptides in a CD16a-binding oligomer of the presentinvention may be separated by a linker. For example, each CD16a-bindingpolypeptide in a CD16a-binding oligomer of the present invention may be separatedby a linker. Preferably, the linker is a linker as defined herein, for example a flexible amino acid linker, a rigid amino acid linker or cleavable amino acid linker or non-amino acid linker, or a synthetic linker. Where a CD16a-binding oligomer of thepresent invention comprises more than one linker, the linkers may be the same, or may be different.Preferably, a linker for a CD16a-binding oligomer of the present invention comprisesor has a sequence of 1 to 50 (for example 1 to 25, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20); and more preferably 1 to 15) naturally occurring amino acids, for example selected from the group consisting of G, S and T (preferably G and S).In one preferred embodiment, a linker for a CD16a-binding oligomer of the presentinvention is G or comprises or has sequence GGGSG, GGGGS, GGSGG, GSGGG and / or SGGGG; for example the linker is G or comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG,GGGSGGGGSGGGGSGGGGSG, GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GGGGSGGGGSGGGGSGGGGS, GGSGG, GGSGGGGSGG, GGSGGGGSGGGGSGG, GGSGGGGSGGGGSGGGGSGGGGSGG, GSGGG, GSGGGGSGGG, GSGGGGSGGGGSGGG, GSGGGGSGGGGSGGGGSGGG, SGGGG, SGGGGSGGGG, SGGGGSGGGGSGGGG, or SGGGGSGGGGSGGGGSGGGG.In one preferred embodiment, a linker for a CD16a-binding oligomer of the presentinvention is G or comprises or has sequence GGGSG; for example the linker comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. In another embodiment, a linker for a CD16a-bindingoligomer of the present invention comprises or has sequence GGGGS; for examplethe linker comprises or has the sequence GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS or GGGGSGGGGSGGGGSGGGGS.Alternatively, CD16a-binding polypeptides in a CD16a-binding oligomer of thepresent invention may not be separated by a linker (i.e. they may be directly attached to each other). In one embodiment, a CD16a-binding oligomer does not comprise a linker.In one embodiment, the CD16a-binding oligomer of the present invention comprisesat least 2 (for example 2) CD16a-binding polypeptides, and the CD16a-bindingoligomer comprises the following structure:[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]- [linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]; wherein each N-terminal portion in the oligomer may have the same sequence or have different sequences; each C-terminal portion in the oligomer may have the same sequence or have different sequences; each separating portion in the oligomer may have the same sequence or have different sequences; each Helix 1 portion in the oligomer may have the same sequence or have different sequences; and each Helix 2 portion in the oligomer may have the same sequence or have different sequences. In such embodiments, the linker preferably comprises or has a sequence of 1 to 25 (for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20; and more preferably 1 to 15) naturally occurring amino acids, for example selected from the group consisting of G, S and T (preferably G and S). For example, the linker is G or comprises or has sequence GGGSG, GGGGS, GGSGG, GSGGG and / or SGGGG; for example wherein the linker is G or comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG, GGGSGGGGSGGGGSGGGGSG, GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GGGGSGGGGSGGGGSGGGGS, GGSGG, GGSGGGGSGG, GGSGGGGSGGGGSGG, GGSGGGGSGGGGSGGGGSGGGGSGG, GSGGG, GSGGGGSGGG, GSGGGGSGGGGSGGG, GSGGGGSGGGGSGGGGSGGG, SGGGG, SGGGGSGGGG, SGGGGSGGGGSGGGG, or SGGGGSGGGGSGGGGSGGGG.In one embodiment, the CD16a-binding oligomer of the present invention comprisesat least 2 (for example 2) CD16a-binding polypeptides, and the CD16a-binding oligomer comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]- [linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]- [linker]-[C-terminal portion]-[Helix 2]-[Separating portion]-[Helix 1]-[N-terminal portion], [C-terminal portion]-[Helix 2]-[Separating portion]-[Helix 1]-[N-terminal portion]- [linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], or [C-terminal portion]-[Helix 2]-[Separating portion]-[Helix 1]-[N-terminal portion]- [linker]-[C-terminal portion]-[Helix 2]-[Separating portion]-[Helix 1]-[N-terminal portion]; wherein each N-terminal portion in the oligomer may have the same sequence or have different sequences; each C-terminal portion in the oligomer may have the same sequence or have different sequences; each separating portion in the oligomer may have the same sequence or have different sequences; each Helix 1 portion in the oligomer may have the same sequence or have different sequences; and eachHelix 2 portion in the oligomer may have the same sequence or have differentsequences; andwherein the linker is attached to any amino acid of the indicated C-terminal portionand / or N-terminal portion of each CD16a binding polypeptide. Preferably the linkeris attached to the terminal amino acid of the indicated C-terminal portion and / or N- terminal portion of each CD16a binding polypeptide, for example attached to theterminus of the terminal amino acid or attached to the side chain of the terminalamino acid. In embodiments where the linker is attached to the N-terminal portion of a CD16abinding polypeptide, preferably the N-terminal portion has the sequence X1X2X3X4X5and the linker is attached at position X1 of the N-terminal portion (for example, atthe N-terminus or at the side chain of position X1(for example wherein X1is lysine)),or at the side chain of position X4 of the [N-terminal portion (for example wherein X4is lysine). In embodiments where the linker is attached to the C-terminal portion of a CD16a binding polypeptide, preferably the C-terminal portion has the sequenceX38X39QSANLLAEAKKLNDAQX56X57X58 and the linker is attached at position X58 of theC-terminal portion (for example, at the C-terminus or at the side chain of position X58(for example wherein X58 is lysine)), or at position X50 of the C-terminal portionwherein X50 is lysine. In one embodiment, the linker is a synthetic linker. For example the linker comprisesone or more groups selected from the group consisting of triazole (especially 1,4- wherein y is 1 to 10 (for example wherein y is 1 to 10 ,

[0002] wherein n is 1 to 30 (for example 1 to 24, 1 to 12, 1 to 10, 1to 8, or 2 to 8 (and especially 2, 3, 4, 8, 12 or 24), and especially 2, 3, 4 or 8). In another embodiment, the linker comprises or has a sequence of 1 to 50 (for example 1 to 25, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20; and more preferably 1 to 15) naturally occurring amino acids, for example selected from the group consisting of G, S and T (preferably G and S).In one preferred embodiment, a linker for a CD16a-binding oligomer of the presentinvention is G or comprises or has sequence GGGSG, GGGGS, GGSGG, GSGGG and / or SGGGG; for example the linker is G or comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG,GGGSGGGGSGGGGSGGGGSG, GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GGGGSGGGGSGGGGSGGGGS, GGSGG, GGSGGGGSGG, GGSGGGGSGGGGSGG, GGSGGGGSGGGGSGGGGSGGGGSGG, GSGGG, GSGGGGSGGG, GSGGGGSGGGGSGGG, GSGGGGSGGGGSGGGGSGGG, SGGGG, SGGGGSGGGG, SGGGGSGGGGSGGGG, or SGGGGSGGGGSGGGGSGGGG.In one preferred embodiment, a linker for a CD16a-binding oligomer of the presentinvention is G or comprises or has sequence GGGSG; for example the linker comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. In another embodiment, a linker for a CD16a-bindingoligomer of the present invention comprises or has sequence GGGGS; for examplethe linker comprises or has the sequence GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS or GGGGSGGGGSGGGGSGGGGS. LinkersWhere present, a linker connects together two or more functional portions (definedfurther herein below) of the polypeptides of the invention. For example, a linker may connect together two CD16a binding polypeptides of the present invention (for example in a CD16a-binding oligomer of the invention), or a linker may connect together a CD16a-binding polypeptide of the present invention and an additional functional portion of the present invention. A linker may also connect together an additional functional portion of the present invention and an additional functional portion of the present invention in embodiments where more than one additional functional portion is present. The skilled person is aware that different kinds of linkers with varying properties are known in the art, and is able to select the appropriate linker(s) depending on the properties desired. Types of linkers include, for example, flexible amino acid linkers, rigid amino acid linkers and cleavable amino acid linkers; non-amino acid linkers may also be used. For example, linkers may be selected to increase stability or improve folding, to increase expression, improve biological activity, enable targeting, or alter pharmacokinetics. A non-amino acidlinker may be referred to as a synthetic linker. An example of a synthetic linker is achemical linker. For the avoidance of doubt, in certain embodiments a linker may not connect together two CD16a binding polypeptides of the present invention (for example in a CD16a-binding oligomer of the invention), and / or a linker may not connect together a CD16a-binding polypeptide of the present invention and an additional functional portion of the present invention; and / or a linker may not connect together an additional functional portion of the present invention and an additional functional portion of the present invention in embodiments where more than one additional functional portion is present. For example, in certain embodiments two CD16a- binding polypeptides of the present invention (for example in a CD16a-binding oligomer of the invention) may be directly connected; and / or a CD16a-binding polypeptide or oligomer of the present invention may be directly connected to an additional functional portion of the present invention; and / or an additionalfunctional portion of the present invention may be directly connected to anadditional functional portion of the present invention. In one embodiment, the CD16a-binding polypeptide according to any aspect disclosed herein, or a CD16a-binding oligomer according to any aspect disclosed herein, further comprises at least one linker, such as at least one linker selected from flexible amino acid linkers, rigid amino acid linkers, cleavable amino acid linkers and synthetic linkers. In one embodiment, said linker is between two or more CD16a- binding polypeptides, for example in a CD16a-binding oligomer of the present invention, or between a CD16a-binding polypeptide or a CD16a-binding oligomer and an additional functional portion, for example an immune signalling molecule or an additional binding moiety (for example as described in further detail below). In one embodiment, the CD16a-binding oligomer according to any aspect disclosed herein comprises at least one linker, such as at least one linker selected from flexible amino acid linkers, rigid amino acid linkers, cleavable amino acid linkers, and synthetic linkers. The linker is between two or more CD16a-binding polypeptides. A further linker between a CD16a-binding polypeptide or a CD16a-binding oligomer and an additional functional portion, for example an immune signalling molecule or an additional binding moiety (for example as described in further detail below), may also be present in a CD16a-binding oligomer according to any aspect disclosed herein. A further linker between an additional functional portion (for example animmune signalling molecule) or an additional binding moiety (for example asdescribed in further detail below) and an additional functional portion (for examplean immune signalling molecule) or an additional binding moiety (for example asdescribed in further detail below), may also be present in a CD16a-binding oligomer according to any aspect disclosed herein. In embodiments and aspects of the present invention that comprise more than one linker, each linker may be the same, or may be different, or some linkers may be the same, and some may be different (for example in embodiments having 3 or more linkers (for example 3, 4, 5, 6, 7, 8 or more linkers)). Flexible linkers may be used when the linked domains require some distance and conformational freedom, and may be advantageous in some embodiments of the invention. Such linkers are generally composed of small, non-polar (for example G) or polar (for example S or T) amino acids. Some flexible linkers primarily consist of stretches of G and S residues, for example (GGGGS)p or (GGGSG)p. Other examples include (GGSGG)p, (GSGGG)p or (SGGGG)p. Adjusting the copy number “p” allows optimization of the linker in order to achieve appropriate separation between the functional moieties, or to maintain necessary inter-moiety interaction. In a preferred embodiment, the linker is (GGGSG)p, for example (GGGSG)1, (GGGSG)2or (GGGSG)3, for example (GGGSG)3. In an embodiment, the linker is (GGGGS)p, for example (GGGGS)1, (GGGGS)2or (GGGGS)3, for example (GGGGS)3. In an embodiment, the linker is (GGSGG)p, for example (GGSGG)1, (GGSGG)2 or (GGSGG)3, for example (GGSGG)3. In an embodiment, the linker is (GSGGG)p, for example (GSGGG)1, (GSGGG)2 or (GSGGG)3, for example (GSGGG)3. In an embodiment, the linker is (SGGGG)p, for example (SGGGG)1, (SGGGG)2 or (SGGGG)3, for example (SGGGG)3. In another, embodiment, the linker is G.In one embodiment, a linker of the present invention comprises or has a sequence of1 to 50 (for example 1 to 40, 1 to 30, or 1 to 25, for example 1, 2, 3, 4, 56, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20; and more preferably 1 to 15) naturally occurring amino acids, for example selected from the groupconsisting of G, S and T. In one embodiment, a linker of the present inventioncomprises or has a sequence of 1 to 50 (for example 1 to 25, for example 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25; or 1 to 20, for example 1, 5, 10, 15 or 20; or 1 to 15, for example 1, 5, 10 or 15) naturally occurring amino acids, for example selected from the group consisting of G and S. For example, a linker of the present invention is G or comprises or has sequence GGGSG; for example the linker comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. Also, for example, a linker of the present invention is G or comprises or has sequence GGGSG, GGGGS, GGSGG, GSGGG and / or SGGGG. For example, the linker is G or comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG, GGGSGGGGSGGGGSGGGGSG, GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GGGGSGGGGSGGGGSGGGGS, GGSGG, GGSGGGGSGG, GGSGGGGSGGGGSGG, GGSGGGGSGGGGSGGGGSGGGGSGG, GSGGG, GSGGGGSGGG, GSGGGGSGGGGSGGG, GSGGGGSGGGGSGGGGSGGG, SGGGG, SGGGGSGGGG, SGGGGSGGGGSGGGG, or SGGGGSGGGGSGGGGSGGGG. In one preferred embodiment, a linker of the present invention is G or comprises or has sequence GGGSG; for example the linker comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. In anotherembodiment, a linker for a CD16a-binding oligomer of the present inventioncomprises or has sequence GGGGS; for example the linker comprises or has the sequence GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS or GGGGSGGGGSGGGGSGGGGS. Most preferably, a linker of the present invention is (GGGSG)n, where n is 1, 2 or 3, and more preferably wherein n is 2 (i.e. a linker of the present invention has the sequence GGGSGGGGSG). Apart from G and S linkers, other flexible linkers are known in the art, such as G and S linkers containing additional amino acid residues, such as T and A, to maintainflexibility, as well as polar amino acid residues to improve solubility. In general, it isknown in the art that linker sequence and length may affect the characteristics of the linked moieties, and so the skilled person will be able to select an appropriate linker for use in the binding polypeptides as described herein. Other types of linkers, such as rigid and / or cleavable linkers, can also be used to connect domains in multidomain constructs to improve or control their biological activity. Such linkers are known in the art (Chen X et al, Fusion protein linkers: Property, design and functionality, Adv Drug Deliv Rev 2013:65:10:1357, doi: 10.1016 / j.addr.2012.09.039). Alternatively, the different binding moieties of the binding polypeptide as described herein (for example two or more CD16a-binding polypeptides, or a CD16a-binding polypeptide and an additional functional portion, for example an immune signalling molecule or an additional binding moiety) may be covalently linked by a chemical linker. Such a chemical linker may be produced by, for example, maleimide or ‘click’ chemistry. The skilled person will be aware of other linkers suitable for use in the binding polypeptides as described herein.A synthetic, or a chemical linker, of the present invention may, for example,comprise one or more group selected from the group consisting of triazole 5 wherein n is 1 to 30 (for example 1 to 24, 1 to 12, 1 to 10, 1 to8, or 2 to 8 (and especially 2, 3, 4, 8, 12 or 24), and especially 2, 3, 4 or 8). In further embodiments, the linker is: With regard to the description above of binding polypeptides comprising a CD16a- binding polypeptide according to the disclosure, it is to be noted that the designation of first, second and further moieties is made for clarity reasons to distinguish between CD16a-binding polypeptide or polypeptides according to the invention on the one hand, and binding moieties exhibiting other functions on the other hand. These designations are not intended to refer to the actual order of the different regions of the binding polypeptide. Similarly, the designations first and second moiety (or monomer unit) are made for clarity reasons to distinguish between said units. Thus, for example, said first moiety (or monomer unit) may without restriction appear at the N-terminal end, in the middle, or at the C-terminal end of the binding polypeptide. In embodiments of the present invention comprising an additional functional portion, the CD16a-binding polypeptide(s) and additional functional portion(s) in aCD16a-binding polypeptide or a CD16a-binding oligomer of the present inventionmay be separated by a linker. For example, each additional functional portion and CD16a-binding polypeptide in a CD16a-binding polypeptide or CD16a-bindingoligomer of the present invention may be separated by a linker. Preferably, thelinker is a linker as defined herein. More preferably, the linker is (GGGSG)n, where n is 1, 2 or 3, and even more preferably the linker is (GGGSG)n, where n is 2 (i.e. a linker has the sequence GGGSGGGGSG). Alternatively, in embodiments of the present invention comprising an additional functional portion, the CD16a-binding polypeptide(s) and additional functionalportion(s) in a CD16a-binding polypeptide or a CD16a-binding oligomer of thepresent invention may be covalently linked by a chemical linker as defined herein.For example, the CD16a-binding polypeptide comprising an additional functional portion may have the structure shown in Figure 9C as L-15 or may have the structure shown in Figure 9C as L-17. In embodiments of the present invention comprising two or more additional functional portions, the additional functional portions may be separated by a linker.Preferably, the linker is a linker as defined herein. More preferably, the linker is(GGGSG)n, where n is 1, 2 or 3, and even more preferably the linker is (GGGSG)n, where n is 2 (i.e. a linker of the present invention is GGGSGGGGSG).Where a CD16a-binding polypeptide or a CD16a-binding oligomer of the presentinvention comprises more than one linker (i.e. wherein there are at least two CD16a- binding polypeptides and at least one additional functional portion; or wherein there is at least one CD16a-binding polypeptides and at least two additional functional portion), the linkers may be the same, or may be different. Preferably, a linker for aCD16a-binding polypeptide or a CD16a-binding oligomer comprising an additionalfunctional portion comprises or has a sequence of 1 to 50 (for example 1 to 25, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20; and more preferably 1 to 15) naturally occurring amino acids, for example selected from the group consisting of G, S and T (preferably G and S). In one preferred embodiment, a linker for a CD16a-binding polypeptide or a CD16a-binding oligomer comprising an additional functional portion is G or comprises or hassequence GGGSG, GGGGS, GGSGG, GSGGG and / or SGGGG; for example the linker comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. In another embodiment, a linker for a CD16a-bindingoligomer of the present invention comprises or has sequence GGGGS; for examplethe linker comprises or has the sequence GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS or GGGGSGGGGSGGGGSGGGGS. In one very preferred embodiment, each linker for a CD16a-binding polypeptide comprising two or more additional functional portions (for example 2 additional functional portions) is G or comprises or has sequence GGGSG, GGGGS, GGSGG,GSGGG and / or SGGGG; for example, the linker comprises or has the sequenceGGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. Inanother embodiment, a linker for a CD16a-binding oligomer of the present inventioncomprises or has sequence GGGGS; for example, the linker comprises or has thesequence GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS or GGGGSGGGGSGGGGSGGGGS. More preferably, each linker is (GGGSG)n, where n is 1, 2 or 3, and more preferably wherein n is 2 (i.e. each linker has the sequence GGGSGGGGSG). Additional functional portions CD16a-binding polypeptides as disclosed herein may be attached, for example via a linker as described herein, to one or more additional functional portions. CD16a- binding oligomers as disclosed herein may be attached, for example via a linker as described hereinabove, to one or more additional functional portions. Therefore, in an embodiment, the at least one CD16a-binding polypeptide (or CD16a-binding oligomer) is attached to one or more additional functional portions, optionally via a linker as described herein. For the avoidance of doubt, a CD16a-binding polypeptide or CD16a-binding oligomer of the present invention may be directly attached to one or more additional functional portions.CD16a-binding polypeptides as disclosed herein may be connected via a linker (forexample one or more linkers) as described herein, to one or more additionalfunctional portions (preferably one or two additional functional portions, and mostpreferably two additional functional portions). CD16a-binding oligomers as disclosedherein may be connected via a linker (for example one or more linkers) as describedherein, to one or more additional functional portions. Therefore, one embodiment ofthe present invention provides a CD16a-binding polypeptide or a CD16a-bindingoligomer as described herein further comprising at least one (i.e. one or more)additional functional portions, wherein the CD16a-binding polypeptide or CD16a-binding oligomer and the additional functional portion are connected by a linker asdescribed herein. For the avoidance of doubt, the term “separated by a linker” as used herein means connected by or connected via a linker. A ‘functional portion’, as used herein, refers to a component or ‘moiety’ with a specific desired biological activity.The one or more (i.e. the at least one) additional functional portion may for examplebe a signalling molecule. Examples of suitable signalling molecules include immune signalling molecules such as cytokines, for example IL-15 and derivatives thereof. The one or more (i.e. at least one) additional functional portion may be one or moreadditional binding moiety(ies), for example one or more binding partner(s)recognising a cell surface protein or antigen, for example an immune cell surfaceprotein or a cell surface tumour antigen (also referred to as a cancer cell surfaceantigen). Cell surface tumour antigens may for example be tumour-associated antigens or tumour-specific antigens. Examples of additional functional portions include additional binding moieties thatare binding partners recognising B-cell maturation antigen (BCMA), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Programmed cell death protein 1 (PD-1),disintegrin and metalloprotease 17 (ADAM17), Programmed death-ligand 1 (PD-L1),SLAM family member 7 (SLAMF7), Epithelial Cell Adhesion Molecule (EPCAM), Epidermal growth factor receptor (EGFR / ErbB-1), Epidermal growth factor receptor variant 3(EGFRvIII),erb-b2 tyrosine kinase 2 (ERBB2 / HER2 / CD340), prostate-specific membrane antigen (PSMA), Claudin8.2 (CLDN18.2), delta like protein 3 (DLL3), mucin 16 (MUC16), mucin 17 (MUC17), mucin 1 (MUC1), Trophoblast glycoprotein (TPBG / 5T4 / WAIF1), V-set domain-containing T-cell activation inhibitor 1 (B7- H4 / VTCN1 / B7x / B7S1), cluster of differentiate 20 (CD20), B-Lymphocyte Surface Antigen B4 (CD19), Sialic Acid-Binding Ig-Like Lectin 2 (CD22), TNF receptor superfamily member 8 (CD30), Natural cytotoxicity triggering receptor 1 (NKp46), orNKG2D. Examples of additional functional portions include additional bindingmoieties that are binding partners recognising a cell surface tumour antigen orcancer cell surface target selected from the group consisting BCMA, ADAM17,SLAMF7, PD-L1, EPCAM, EGFR / ErbB-1, EGFRvIII, ERBB2 / HER2 / CD340, PSMA, CLDN18.2, DLL3, MUC16, MUC17, MUC1, TPBG / 5T4 / WAIF1 and B7- H4 / VTCN1 / B7x / B7S1. Examples of additional functional portions include additional binding moieties that are binding partners recognising an immune cell surfaceprotein or immune cell surface target selected from the group consisting of CTLA-4,PD-1, NKp46, NKG2D, CD20, CD19, CD22 and CD30. Examples of additional functionalportions include additional binding moieties that are binding partners recognising acell surface tumour antigen or cancer cell surface target expressed in haematologicalmalignancies, for example BCMA, CD20, CD19, CD22 or CD30. (For the avoidance ofdoubt, such examples of additional binding moieties, for example binding partnersrecognising cell surface proteins or antigens, are non-limiting and are specified hereby way of illustration.) The additional binding moiety as referred to in this context isnot a CD16a binding polypeptide of the present invention.In embodiments of the present invention a CD16a-binding polypeptide or CD16a-binding oligomer of the present invention further comprises at least one (i.e. one ormore) additional functional portion (for example one or more additional bindingmoiety(ies) and / or signalling molecule), wherein the CD16a-binding polypeptide orCD16a-binding oligomer and each additional functional portion are separated by alinker as described above. For example, the CD16a-binding polypeptide or CD16a-binding oligomer further comprises to one, two, three, four or more additionalfunctional portions (for example one, two, three, four or more additional bindingmoieties and / or signalling molecules). In certain preferred embodiments, the CD16a-binding polypeptide or CD16a-binding oligomer further comprises one or twoadditional functional portions (for example one or two additional binding moieties orsignalling molecules). In one preferred embodiment, the CD16a-binding polypeptideor CD16a-binding oligomer further comprises one additional functional portion (forexample one additional binding moiety or signalling molecule). In one especiallypreferred embodiment, the CD16a-binding polypeptide or CD16a-binding oligomerfurther comprises two additional functional portions (for example two additionalbinding moiety(ies) or signalling molecules).In certain preferred embodiments, an additional functional portion is a signalling molecule. A signalling molecule, for example an immune signalling molecule such asa cytokine, for example IL-15 or derivatives thereof, may be attached at the N-terminal end or the C-terminal end of a CD16a-binding polypeptide or a CD16a-binding oligomer, separated by a linker as described herein. One or more signalling molecule(s) may, alternatively, be attached between two CD16a-bindingpolypeptides in a CD16a-binding oligomer separated from each CD16a-bindingpolypeptide by a linker as described herein. Preferably, the signalling molecule(s) may be attached at the N-terminal portion (for example the N-terminus) or the C-terminal portion (for example the C-terminus) of a CD16a-binding polypeptide or aCD16a-binding oligomer via a linker as described above.In certain preferred embodiments, an additional functional portion is an additional binding moiety. For example, an additional functional portion is an additional binding moiety that is a binding partner recognising one of the following: CTLA-4, PD-1, BCMA, ADAM17, PD-L1, SLAMF7, EPCAM, EGFR / ErbB-1, EGFRvIII, ERBB2 / HER2 / CD340, PSMA, CLDN18.2, DLL3, MUC16, MUC17, MUC1, TPBG / 5T4 / WAIF1, B7-H4 / VTCN1 / B7x / B7S1, CD20, CD19, CD22 or CD30. For example, an additional functional portion is an additional binding moiety that is specific for one of the following: CTLA-4, PD-1, BCMA, ADAM17, PD-L1, SLAMF7, EPCAM, EGFR / ErbB-1, EGFRvIII, ERBB2 / HER2 / CD340, PSMA, CLDN18.2, DLL3, MUC16, MUC17, MUC1, TPBG / 5T4 / WAIF1, B7-H4 / VTCN1 / B7x / B7S1, CD20, CD19, CD22 or CD30. In certain preferred embodiments, an additional binding moiety is specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). In certain preferred embodiments, an additional binding moiety is specificfor an immune cell surface target (for example a NK cell target, for example NKp46,NKG2D, PD-1, etc).An additional binding moiety, for example a binding partner recognising the cellsurface tumour antigen BCMA, may be attached at the N-terminal portion (forexample the N-terminus) or the C-terminal portion (for example the C-terminus) of aCD16a-binding polypeptide or a CD16a-binding oligomer, separated by a linker asdescribed herein. The one or more additional binding moiety(ies) may, alternatively,be attached between two CD16a-binding polypeptides in a CD16a-binding oligomerseparated from each CD16a-binding polypeptide by a linker as described herein. Preferably, the additional binding moiety(ies), for example a binding partner recognising the cell surface tumour antigen BCMA, may be attached at the N- terminal portion (for example the N-terminus) or the C-terminal portion (for example the C-terminus) of a CD16a-binding polypeptide or a CD16a-bindingoligomer, separated by a linker as described above. More preferably, the additionalbinding moiety(ies), for example a binding partner recognising the cell surface tumour antigen BCMA, may be attached at the N-terminal portion (for example the N-terminus) or the C-terminal portion (for example the C-terminus) of a CD16a-binding polypeptide or a CD16a-binding oligomer, separated by a linker as describedabove. The present inventors have surprisingly found that a ‘dual engager’ polypeptidecomprising a CD16a-binding polypeptide of the present invention and at least oneadditional functional portion as disclosed herein, can retain its CD16a binding ability when fused to an additional binding moiety targeting the myeloma antigen BCMA. This ‘dual engager’ polypeptide comprising a CD16a-binding polypeptide as disclosedherein attached to a BCMA-binding moiety is also surprisingly capable of activatingNK cells in the presence of BCMA-expressing tumour cells and surprisingly capable ofinhibiting tumour growth in an in vivo multiple myeloma model. In one preferred embodiment, the CD16a-binding polypeptide or CD16a-binding oligomer of the present invention further comprises one or more additional functional portions, for example at least one, at least two, at least three or at least four additional functional portions. For example, in particular embodiments, the CD16a-binding polypeptide or CD16a-binding oligomer of the present inventionfurther comprises 1, 2, 3, 4 or 5 additional functional portions. In especially preferredembodiments, the CD16a-binding polypeptide or CD16a-binding oligomer of the present invention further comprises one, two or three additional functional portions,and more preferably one or two, and most especially two additional functionalportions. In especially preferred embodiments, the CD16a-binding polypeptide orCD16a-binding oligomer of the present invention further comprises one or two (preferably two) additional functional portions, wherein each additional functionalportion is a BCMA-binding polypeptide. In very especially preferred embodiments,the CD16a-binding polypeptide of the present invention further comprises one or two (preferably two) additional functional portions, wherein each additional functional portion is a BCMA-binding polypeptide. In embodiments wherein the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least two, at least three or at least four additional functional portions (for example 2, 3, 4 or 5 additional functional portions), each additional functional portion may be the same, or may be different, or some additional functional portionsmay be the same, and some additional functional portions may be different (forexample in embodiments having at least 3 or at least 4 additional functional portions (for example 3, 4, 5, 6 or more additional functional portions)). In embodiments wherein the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least two, at least three or at least four additional functional portions (for example 2, 3, 4 or 5 additional functional portions), each additional functional portion may have the same function, or may have different functions, or someadditional functional portions may have the same function, and some may havedifferent functions (for example in embodiments having at least 3 or at least 4 additional functional portions (for example 3, 4, 5, 6 or more additional functional portions)). In embodiments wherein the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least two, at least three or at least four additional functional portions(for example 2, 3, 4 or 5 additional functional portions), a first additional functionalportion may comprise an additional binding moiety (for example an additionalbinding moiety specific for a cancer cell surface target, for example a myeloma cellsurface antigen, for example BCMA, or that is specific for an immune cell target, forexample a NK cell target); and a second additional functional portion may comprisean immune signalling molecule, for example a cytokine, for example IL-15 orderivatives thereof. For example, in one preferred embodiment, a first additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA) and a second additional functional portion may comprise a cytokine, for example IL-15 or derivatives thereof. In particular, a first additional functional portion maycomprise an additional binding moiety specific for BCMA; and a second additionalfunctional portion may comprise a cytokine, for example IL-15 or derivatives thereof.Alternatively, for example, in one preferred embodiment, a first additional functionalportion may comprise an additional binding moiety specific for an immune cell target(for example a NK cell target) and a second additional functional portion may comprise a cytokine, for example IL-15 or derivatives thereof. In particular, a first additional functional portion may comprise an additional binding moiety specific for a NK cell target; and a second additional functional portion may comprise a cytokine, for example IL-15 or derivatives thereof. The inventors have surprisingly found that heterotrimeric CD16a-binding polypeptides disclosed herein (i.e. comprising a CD16a-binding polypeptide disclosed herein and two additional functional portions which are hBCMA-binding polypeptides as disclosed herein) are particularly effective in engaging NK cells and triggering ADCC-mediated cancer cell killing, compared to corresponding heterodimeric CD16a-binding polypeptides (i.e. comprising the same CD16a-binding polypeptide and one additional functional portion which is an hBCMA-binding polypeptide as disclosed herein). This effect is particularly pronounced for heterotrimeric CD16a-binding polypeptides of the invention compared to comparator heterotrimeric CD16a-binding polypeptides.Therefore, in a very preferred embodiment, a first additional functional portion maycomprise an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen,for example BCMA, or specific for an immune cell target, for example a NK celltarget); and a second additional functional portion may comprise an additional binding moiety (for example an additional binding moiety specific for a cancer cellsurface target, for example a myeloma cell surface antigen, for example BCMA, orspecific for an immune cell target, for example a NK cell target). For example, a first additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA); and a second additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). In particular, a first additional functional portion may comprise an additional binding moiety specific for BCMA; and a second additional functional portion may comprise an additional binding moiety specific for BCMA. Alternatively, for example, a first additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA); and a second additional functional portion may comprise an additional binding moiety specific for an immunecell surface target (for example a NK cell target). In particular, a first additionalfunctional portion may comprise an additional binding moiety specific for BCMA; and a second additional functional portion may comprise an additional binding moiety specific for a NK cell target. In another embodiment, a first additional functional portion may comprise animmune signalling molecule, for example a cytokine, for example IL-15 or derivativesthereof; and a second additional functional portion may comprise an immunesignalling molecule, for example a cytokine, for example IL-15 or derivatives thereof.When present (for example in embodiments wherein the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least three or at least four additionalfunctional portions (for example 3, 4 or 5)), a third additional functional portion maycomprise an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or specific for an immune cell target, for example a NK cell target), or comprises an immune signalling molecule, for example a cytokine, forexample IL-15 or derivatives thereof. Preferably, when present, a third additionalfunctional portion may comprise an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or specific for an immune celltarget, for example a NK cell target; and especially an additional binding moietyspecific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA). When present (for example in embodiments wherein the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least four additional functional portions (forexample 4 or 5)), a fourth additional functional portion may comprise an additionalbinding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or specific for an immune cell target, for example a NK cell target), or comprise animmune signalling molecule, for example a cytokine, for example IL-15 or derivativesthereof. Preferably, when present, a fourth additional functional portion may comprise an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or specific for an immune cell target, for example a NK cell target; and especially an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA). When present (for example in embodiments wherein the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least five additional functional portions (forexample 5 or 6)), a fifth additional functional portion may comprise an additionalbinding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or is specific for an immune cell target, for example a NK cell target), or comprises an immune signalling molecule, for example a cytokine, for example IL-15 or derivatives thereof.In one preferred embodiment, in which the CD16a-binding polypeptide or CD16a-binding oligomer comprises at least three (for example 3, 4 or 5) additional functional portions, a first additional functional portion may comprise an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or specific for an immune cell target, for example a NK cell target); a second additional functional portion may comprise an immune signalling molecule, for example acytokine, for example IL-15 or derivatives thereof; and a third additional functionalportion may comprise an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or specific for an immune cell target, for example a NK cell target). In one embodiment, a first additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA); and a second additional functional portion maycomprise a cytokine, for example IL-15 or derivatives thereof; and a third additionalfunctional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA)or an immune cell target (for example a NK cell target). In particular, a first additionalfunctional portion may comprise an additional binding moiety specific for BCMA; anda second additional functional portion may comprise a cytokine, for example IL-15 orderivatives thereof; and a third additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). In another embodiment, a first additional functional portion may comprise an additional binding moiety specific for BCMA; and a second additional functional portion may comprise a cytokine, for example IL-15 or derivatives thereof; and a third additional functional portion may comprise an additional binding moiety specific for an immune cell target (for example a NK cell target). For example, a first additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA); and a second additional functional portion maycomprise an additional binding moiety specific for a cancer cell surface target (forexample a myeloma cell surface antigen, for example BCMA); and a third additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA)or an immune cell target (for example a NK cell target). In particular, a first additionalfunctional portion may comprise an additional binding moiety specific for BCMA; and a second additional functional portion may comprise an additional binding moiety specific for BCMA; and a third additional functional portion may comprise an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). In another embodiment, a first additional functional portion may comprise an additional binding moiety specific for BCMA; and a second additional functional portion may comprise an additional binding moiety specific for BCMA; and a third additional functional portion may comprise an additional binding moiety specific for an immune cell target (for example a NK cell target).In one embodiment, a CD16a-binding polypeptide or CD16a-binding oligomercomprising an additional binding moiety of the present invention has an additional binding moiety separated from the CD16a-binding polypeptide or the CD16a-binding oligomer by a linker. A linker may be any linker defined hereinabove. For example, a linker selected from flexible amino acid linkers, rigid amino acid linkers, cleavableamino acid linkers and synthetic linkers.Preferably, a linker for a CD16a-binding polypeptide or CD16a-binding oligomercomprising an additional binding moiety comprises or has a sequence of 1 to 50 (for example 1 to 25, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20; and more preferably 1 to 15) naturally occurring amino acids, for example selected from the group consisting of G, S and T (preferably G and S).In one preferred embodiment, a linker for a CD16a-binding polypeptide or CD16a-binding oligomer comprising an additional binding moiety of the present invention is G or comprises or has the sequence GGGSG, GGGGS, GGSGG, GSGGG and / or SGGGG; for example the linker is G or comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSGGGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GGGGSGGGGSGGGGSGGGGS, GGSGG, GGSGGGGSGG, GGSGGGGSGGGGSGG, GGSGGGGSGGGGSGGGGSGGGGSGG, GSGGG, GSGGGGSGGG, GSGGGGSGGGGSGGG, GSGGGGSGGGGSGGGGSGGG, SGGGG, SGGGGSGGGG, SGGGGSGGGGSGGGG, or SGGGGSGGGGSGGGGSGGGG.In one preferred embodiment, a linker for a CD16a-binding polypeptide comprisingan additional binding moiety of the present invention is G or comprises or has thesequence GGGSG; for example, the linker comprises or has the sequence GGGSG,GGGSGGGGSG, GGGSGGGGSGGGGSG or GGGSGGGGSGGGGSGGGGSG. In anotherembodiment, a linker for a CD16a-binding oligomer of the present inventioncomprises or has the sequence GGGGS; for example, the linker comprises or has thesequence GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS or GGGGSGGGGSGGGGSGGGGS. More preferably, the linker is (GGGSG)n, where n is 1, 2 or 3, and even more preferably the linker is (GGGSG)n, where n is 2 (i.e. a linker hasthe sequence GGGSGGGGSG). Alternatively, in one embodiment, a CD16a-bindingpolypeptide or CD16a-binding oligomer comprising an additional binding moiety of the present invention has an additional binding moiety that is not separated from the CD16a-binding polypeptide or the CD16a-binding oligomer by a linker (i.e. theCD16a-binding polypeptide or CD16a-binding oligomer is directly attached to anadditional binding moiety).In one embodiment, a CD16a-binding polypeptide or CD16a-binding oligomercomprising an additional binding moiety of the present invention does not comprisea linker. In one embodiment, the CD16a-binding polypeptide or CD16a-bindingoligomer is directly attached to an additional binding moiety.In certain embodiments, a CD16a-binding polypeptide of the present inventioncomprising an additional functional portion comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]; [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]; [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]- [additional functionalportion], (for example [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C- terminal portion]-[linker]-[additional functional portion]-[linker]-[additional functional portion]); [additional functional portion]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], (for example [additional functional portion]-[linker]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]- [C-terminal portion]); or [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]; wherein, when more than one additional functional portion is present, each additional functional portion may be the same, or may be different.In such embodiments, the linker (or linkers) preferably comprises or has a sequenceof 1 to 25 (for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurring amino acids; and preferably 1 to 20 (for example 1, 5, 10, 15, or 20; and more preferably 1 to 15) naturally occurring amino acids, for example selected from the group consisting of G, S and T (preferably G andS). For example, the linker is G or comprises or has the sequence GGGSG, GGGGS,GGSGG, GSGGG and / or SGGGG; for example the linker is G or comprises or has the sequence GGGSG, GGGSGGGGSG, GGGSGGGGSGGGGSG, GGGSGGGGSGGGGSGGGGSG, GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GGGGSGGGGSGGGGSGGGGS, GGSGG, GGSGGGGSGG, GGSGGGGSGGGGSGG, GGSGGGGSGGGGSGGGGSGGGGSGG, GSGGG, GSGGGGSGGG, GSGGGGSGGGGSGGG, GSGGGGSGGGGSGGGGSGGG, SGGGG, SGGGGSGGGG, SGGGGSGGGGSGGGG, or SGGGGSGGGGSGGGGSGGGG. Alternatively, the linker may be absent, i.e. the CD16a-binding polypeptide or CD16a-binding oligomer comprises the following structure:[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[additional functional portion]; [additional functional portion]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]; [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[additional functional portion]- [additional functional portion];[additional functional portion]-[additional functional portion]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]; or [additional functional portion]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[additional functional portion].More preferably the CD16a-binding polypeptide comprises the following structure:[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]; [additional functional portion]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], (for example [additional functional portion]-[linker]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]- [C-terminal portion]); or [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]; or comprises the following structure: [additional functional portion]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] [additional functional portion]-[additional functional portion]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], (for example [additional functional portion]-[linker]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]- [C-terminal portion]); or[additional functional portion]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[additional functional portion]). In such embodiments, preferably each additional functional portion is an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). Most preferably each additional functional portion is an additional binding moiety specific for BCMA.Even more preferably, the CD16a-binding polypeptide comprises the followingstructure: [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]; or [additional functional portion]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], (for example [additional functional portion]-[linker]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]- [C-terminal portion]). In such embodiments, preferably each additional functional portion is an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). Most preferably each additional functional portion is an additional binding moiety specific for BCMA, In one very especially preferred embodiment of the invention the CD16a-binding polypeptide comprises the following structure: [additional functional portion]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion].For example the CD16a-binding polypeptide comprises the following structure:[additional functional portion]-[linker]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]. In such embodiments, preferably each additional functional portion is an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). Most preferably each additional functional portion is an additional binding moiety specific for BCMA. Optionally, in such embodiments, the linker may be absent. In another very especially preferred embodiment of the invention the CD16a-binding polypeptide consists of the following structure: [additional functional portion]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion].For example, the CD16a-binding polypeptide consists of the following structure:[additional functional portion]-[linker]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]. In such embodiments, preferably each additional functional portion is an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). Most preferably each additional functionalportion is an additional binding moiety specific for BCMA. Optionally, in suchembodiments, the linker may be absent.In certain embodiments, a CD16a-binding polypeptide of the present inventioncomprising an additional functional portion comprises the following structure:[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]; [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]; [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]-[additional functional portion], (for example [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C- terminal portion]-[linker]-[additional functional portion]-[linker]-[additional functional portion]); [additional functional portion]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], (for example [additional functional portion]-[linker]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]- [C-terminal portion]); or[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion];wherein, the linker, or each linker, is a linker as described herein;wherein when more than one additional functional portion is present, eachadditional functional portion may be the same, or may be different; andwherein the linker, or each linker, is attached to any amino acid of the indicated [C-terminal portion] and / or [N-terminal portion] of the CD16a-binding polypeptide.The linker, or a linker (for example each linker), may be a linker as defined herein.For example an amino acid linker as defined herein (for example a linker that preferably comprises or has a sequence of 1 to 25 (for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) naturally occurringamino acids) or a synthetic linker as described herein. The linker, or a linker, may beattached to the terminal amino acid of the indicated [C-terminal portion] and / or [N- terminal portion] of the CD16a-binding polypeptide, for example attached to the terminus of the terminal amino acid or attached to the side chain of the terminal amino acid (for example attached to the side chain of a terminal lysine). In embodiments where the linker is attached to the [N-terminal portion] of a CD16a- binding polypeptide, preferably the N-terminal portion has the sequence X1X2X3X4X5and the linker is attached at position X1of the [N-terminal portion] (for example, at the N-terminus or at the side chain of position X1(for example wherein X1is lysine)), or at the side chain of position X4of the [N-terminal portion] (for example wherein X4is lysine). In embodiments where the linker is attached to the [C-terminal portion] of a CD16a- binding polypeptide, preferably the C-terminal portion has the sequenceX38X39QSANLLAEAKKLNDAQX56X57X58 and the linker is attached at position X58 of the[C-terminal portion] (for example, at the C-terminus or at the side chain of position X58(for example wherein X58is lysine)), or at position X50of the [C-terminal portion] wherein X50is lysine.In one embodiment the linker, or a linker (for example each linker), is attached to anon-terminal amino acid of the indicated [C-terminal portion] and / or [N-terminal portion] of the CD16a-binding polypeptide, for example attached to the side chain of a non-terminal amino acid (for example attached to the side chain of a non-terminal lysine, for example a lysine at X4 of the [N-terminal portion] in embodiments whereinthe [N-terminal portion] has the sequence X1X2X3X4X5, or for example a lysine at X50of the [C-terminal portion] in embodiments wherein the [C-terminal portion] has thesequence X38X39QSANLLAEAKKLNDAQX56X57X58). When more than one additional functional portion is present and the additionalfunctional portions are attached (i.e. the CD16a-binding polypeptide comprises thestructure “[additional functional portion]-[additional functional portion]”), theadditional functional portions may be separated by a linker (i.e connected by orconnected via a linker), and preferably separated by a linker of the present invention. When more than one linker is present, each linker may be the same, or may be different.Most preferably, the CD16a-binding polypeptide of the present invention comprisestwo additional functional portions and comprises the following structure: [additional functional portion]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion].For example, CD16a-binding polypeptide of the present invention comprises twoadditional functional portions and comprises the following structure: [additional functional portion]-[linker]-[additional functional portion]-[linker]- [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion].In such embodiments, preferably the [Helix 1]-[Separating portion]-[Helix 2] is SEQ IDNO: 1. In such embodiments, preferably no residues in the sequence are replaced byan alternative residue.Alternatively, in such embodiments, preferably the [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] is SEQ ID NO: 2 or 3. In suchembodiments, preferably no residues in the sequence are replaced by an alternative residue.In one very especially preferred embodiment, the CD16a-binding polypeptide of thepresent invention comprises two additional functional portions and comprises the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5).In such an embodiment, preferably no residues in the sequence are replaced by an alternative residue.In another very especially preferred embodiment, the CD16a-binding polypeptide ofthe present invention comprises two additional functional portions and has thesequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5).In such an embodiment, preferably no residues in the sequence are replaced by an alternative residue.In another preferred embodiment, the CD16a-binding polypeptide of the presentinvention comprises two additional functional portions and comprises the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 6).In such an embodiment, preferably no residues in the sequence are replaced by an alternative residue.In another preferred embodiment, the CD16a-binding polypeptide of the presentinvention comprises two additional functional portions and has the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 6).In such an embodiment, preferably no residues in the sequence are replaced by an alternative residue.In another embodiment, the CD16a-binding polypeptide comprises the followingstructure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]; or [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion];and even more preferably comprises the following structure:[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]; wherein, the linker is a linker as described herein; andwherein the linker is attached to any amino acid of the indicated [C-terminal portion]or [N-terminal portion] of the CD16a-binding polypeptide. Preferably the linker is attached to the terminal amino acid of the indicated [C- terminal portion] or [N-terminal portion] of the CD16a-binding polypeptide, for example attached to the terminus of the terminal amino acid or attached to the side chain of the terminal amino acid (for example attached to the side chain of a terminal lysine). In another embodiment the linker is attached to a non-terminal amino acid of the indicated [C-terminal portion] or [N-terminal portion] of the CD16a-binding polypeptide, for example attached to the side chain of a non-terminal amino acid (for example attached to the side chain of a non-terminal lysine, for example a lysine at X4 of the [N-terminal portion] in embodiments wherein the [N-terminal portion] has the sequence X1X2X3X4X5, or for example a lysine at X50 of the[C-terminal portion] in embodiments wherein the [C-terminal portion] has thesequence X38X39QSANLLAEAKKLNDAQX56X57X58). In embodiments wherein a CD16a-binding polypeptide of the present inventioncomprises an additional functional portion and comprises the following structure:[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]; [additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]; [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion]-[additional functional portion], (for example N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C- terminal portion]-[linker]-[additional functional portion]-[linker]-[additional functional portion]; [additional functional portion]-[additional functional portion]-[linker]-[N- terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion], (for example [additional functional portion]-[linker]-[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]- [C-terminal portion]); or[additional functional portion]-[linker]-[N-terminal portion]-[Helix 1]- [Separating portion]-[Helix 2]-[C-terminal portion]-[linker]-[additional functional portion];each additional functional portion may preferably be an additional binding moietyspecific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA). More preferably each additional functional portion is an additional binding moiety specific for BCMA. Even more preferably, each additional functional portion is an additional bindingmoiety specific for hBCMA that is a hBCMA-binding polypeptide, and whichcomprises at least one motif that binds to hBCMA, wherein said polypeptide comprises the following structure: [hBCMA N-terminal portion]-[hBCMA Helix 1]-[hBCMA Separating portion]- [hBCMA Helix 2]-[hBCMA C-terminal portion]; the hBCMA binding motif being the portion [hBCMA Helix 1]-[hBCMA Separating portion]-[hBCMA Helix 2]. Even more preferably, such a hBCMA-binding polypeptideis a hBCMA-binding polypeptide as defined in International Application No.PCT / EP2023 / 064625, the contents of which are incorporated herein by reference. For example, in one very especially preferred embodiment, the present inventionprovides a CD16a-binding polypeptide which comprises the following structure:[BCMA-binding polypeptide]-[Linker 1]-[BCMA-binding polypeptide]-[Linker 2]-[CD16a-binding polypeptide]; wherein: each of the BCMA-binding polypeptides comprises the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide comprises the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or comprises the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 has the sequence (GGGSG)n, where n is 1, 2 or 3. In such embodiments, preferably n is 2. Additionally, or alternatively, preferably the CD16a-binding polypeptide comprises the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2).Also preferably, in such embodiments no residues in the sequence are replaced byan alternative residue.Also, for example, in another very especially preferred embodiment, the presentinvention provides a CD16a-binding polypeptide which comprises the followingstructure: [BCMA-binding polypeptide]-[Linker 1]-[BCMA-binding polypeptide]-[Linker 2]-[CD16a-binding polypeptide]; wherein: each of the BCMA-binding polypeptides consists of the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide consists of the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or consists of the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 consists of the sequence (GGGSG)n, where n is 1, 2 or 3. In such embodiments, preferably n is 2. Additionally, or alternatively, preferably the CD16a-binding polypeptide consists of the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2).Also preferably, in such embodiments no residues in the sequence are replaced byan alternative residue.In one preferred embodiment, the CD16a-binding polypeptide comprises or has thesequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5);or the polypeptide comprises or has the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 6).In such an embodiment, preferably no residues in the sequence are replaced by analternative residue.More preferably, the CD16a-binding polypeptide comprises or has the sequence:VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5).In such an embodiment, preferably no residues in the sequence are replaced by analternative residue.Even more preferably, the CD16a-binding polypeptide has the sequence:VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP KGGGSGGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5).In such an embodiment, preferably no residues in the sequence are replaced by analternative residue. In the above embodiments defining the structure of the CD16a-binding polypeptide or CD16a-binding oligomer comprising an additional functional portion, each additional functional portion may be any one described herein. For example, each additional functional portion may be independently selected from: an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA, or an immune cell target, for example a NK cell target); and an immune signalling molecule, for example a cytokine, for example IL-15 orderivatives thereof. For example, each additional functional portion may be independently selected from: an additional binding moiety specific for a cancer cell surface target (for example a myeloma cell surface antigen, for example BCMA); an additional binding moiety specific for an immune cell target (for example a NK cell target); andan immune signalling molecule, for example a cytokine, for example IL-15 orderivatives thereof. For example, each additional functional portion may be independently selected from: an additional binding moiety specific for BCMA; an additional binding moiety specific for a NK cell target; andan immune signalling molecule, for example a cytokine, for example IL-15 orderivatives thereof. For example, each additional functional portion may be independently selected from: an additional binding moiety specific for BCMA; and an additional binding moiety specific for a NK cell target; anda cytokine, for example IL-15 or derivatives thereof.For example, each additional functional portion may be independently selected from: an additional binding moiety specific for BCMA; and an additional binding moiety specific for a NK cell target; andIL-15 or derivatives thereof.In one preferred embodiment, each additional functional portion may be independently selected from: an additional binding moiety specific for BCMA; and an additional binding moiety specific for a NK cell target; anda cytokine, for example IL-15 or derivatives thereof. In one preferred embodiment, each additional functional portion may be independently selected from: an additional binding moiety specific for BCMA; and an additional binding moiety specific for a NK cell target. In one preferred embodiment, each additional functional portion is an additional binding moiety specific for BCMA. In the above embodiments defining the structure of the CD16a-binding polypeptide or CD16a-binding oligomer comprising an additional functional portion, each additional functional portion may be an additional binding moiety (for example an additional binding moiety specific for a cancer cell surface target, for example a myeloma cell surface antigen, for example BCMA). For example, each additional functional portion may be an additional binding moiety for BCMA. In a preferred embodiment, an additional binding moiety for BCMA is a hBCMA- binding polypeptide which comprises at least one motif that binds to hBCMA, wherein said hBCMA-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion]; the hBCMA binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]. For example, the hBCMA-binding polypeptide is a hBCMA-binding polypeptide as defined in the International Application No. PCT / EP2023 / 064625. The contents of that PCT application are herein incorporated by reference. In particular, the hBCMA-binding polypeptide is one wherein: i) Helix 1 comprises the sequence X9X10X11ADX14EIX17X18and Helix 2 comprises the sequence FX25QKWAFX31RX33LX35, wherein, independently from each other, a) X9and X10are any naturally occurring amino acid; X11is E, F, H, Q, T or Y; X14is any naturally occurring amino acid; X17is A, E, Q, S, T or V; X18is any naturally occurring amino acid; X25is F or Y; X31is I, M, or V; X33is K or S; X35is I, L, M, or V; or ii) Helix 1 and Helix 2 are defined as in i), wherein within Helix 1 and Helix 2, at least 1 and no more than 5 (for example at least 1 and no more than 3) of the Xn residues are replaced by an alternative residue, and / or at least 1 and no more than 5 (for example at least 1 and no more than 3) of the residues not labelled as Xnare replaced by an alternative residue. For example, the hBCMA-binding polypeptide is one with hBCMA binding efficacy is of at least 1% of the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4). In a very preferred embodiment, the hBCMA-binding polypeptide is the polypeptide of SEQ ID NO: 4. In another very preferred embodiment, the hBCMA-binding polypeptide is a polypeptide comprising (or having) a sequence selected from the group consisting ofSEQ ID NO: 23 to 31 (Example ID 1027-1035) of Figure 4 and a sequence of Table 3below, or a derivative thereof (for example wherein from 1 to 5 (for example 1, 2 or3) amino acid residues are replaced by an alternative residue, for example a differentnaturally occurring amino acid or a different unnatural amino acid; or a different naturally occurring amino acid excluding methionine or a different unnatural amino acid). Table 3: hBCMA-binding polypeptide sequences SEQ ID NO:Name Sequence39 Fa-G6VDNKFNKEETFADLEISNLPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK 41-E6VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK 40 Fa-G6 E9AGSSHHHHHHYYLEVDNKFNKEATFADLEISNLPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 41 Fa-G6 T10AGSSHHHHHHYYLEVDNKFNKEEAFADLEISNLPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 42 Fa-G6 F11AGSSHHHHHHYYLEVDNKFNKEETAADLEISNLPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 43 Fa-G6 D13AGSSHHHHHHYYLEVDNKFNKEETFAALEISNLPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 44 Fa-G6 L14AGSSHHHHHHYYLEVDNKFNKEETFADAEISNLPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 45 Fa-G6 S17AGSSHHHHHHYYLEVDNKFNKEETFADLEIANLPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 46 Fa-G6 N18AGSSHHHHHHYYLEVDNKFNKEETFADLEISALPNLNFYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 47 Fa-G6 F24AGSSHHHHHHYYLEVDNKFNKEETFADLEISNLPNLNAYQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK 48 Fa-G6 Y25AGSSHHHHHHYYLEVDNKFNKEETFADLEISNLPNLNFAQKWAFIRSL MDDPSQSANLLAEAKKLNDAQAPKFa-G6 K27AGSSHHHHHHYYLEVDNKFNKEETFADLEISNLPNLNFYQAWAFIRSL MDDPSQSANLLAEAKKLNDAQAPK Fa-G6 VDNKFNKEETFADLEISNLPNLNFYQKAAFIRSLMDDPSQSANLLAE W28A AKKLNDAQAPKFa-G6 I31AGSSHHHHHHYYLEVDNKFNKEETFADLEISNLPNLNFYQKWAFARS LMDDPSQSANLLAEAKKLNDAQAPKFa-G6 R32AGSSHHHHHHYYLEVDNKFNKEETFADLEISNLPNLNFYQKWAFIASL MDDPSQSANLLAEAKKLNDAQAPK Fa-G6 GSSHHHHHHYYLEVDNKFNKEETFADLEISNLPNLNFYQKWAFIRSL M35A ADDPSQSANLLAEAKKLNDAQAPK 1-E1VDNKFNKEEIFADREIAFLPNLNFYQKWAFIRKLMDDPSQSANLLAE AKKLNDAQAPK 1-A5VDNKFNKESQFADEEIEALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 1-A7VDNKFNKEQEFADYEIATLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 1-F9VDNKFNKEDSFADTEIAKLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 1-F10GDNKFNKEEIFADQEIEALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 2-B1VDNKFNKEDYFADYEIATLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 2-C4VDNKFNKEEQFADEEIAHLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 2-D3VDNKFNKESMFADIEITKLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 2-H2VDNKFNKEEVFADEEIASLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 2-A7VDNKFNKEVREADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 2-E5VDNKFNKEHQFADYEIAMLPNLNFYQKWAFIRSLMDDPSQSANLL AEAKKLNDAQAPK 2-E6VDNKFNKEHFFADKEIAKLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 2-G5VDNKFNKEKAFADTEIVNLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 2-A10VDNKFNKESEFADAEIANLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 2-B10GDNKFNKEENFADHEIALLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 2-C5VDNKFNKEDSHADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 2-D10VDNKFNKESKFADEEIAKLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 1-E2VDNKFNKESSADLEIAHLPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK1-A2VDNKFNKEQQFADEEIAMLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK1-B1VDNKFNKEHHFADIEISHLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-B2VDNKFNKESQFADQEIAALPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK1-B3VDNKFNKEEYFADSEIAQLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-C1VDNKFNKEEKFADVEIAYLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-C2VDNKFNKETEFADSEIVRLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-C3VDNKFNKETTFADQEIASLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-D1VDNKFNKEYKFADYEIVALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-D2VDNKFNKEFQFADIEIAELPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK1-D3VDNKFNKEQTFADQEIAELPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-E3VDNKFNKETSFADKEIALLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-F1VDNKFNKERMFADIEIQQLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-F2VDNKFNKEIMFADQEIVSLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-F3VDNKFNKETQFADQEIAFLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-G1VDNKFNKELDFADQEIAYLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-G2VDNKFNKELIFADEEIVALPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK1-H1VDNKFNKEHFFADSEIAALPNLNFYQKWAFVRSLMDDPSQSANLL AEAKKLNDAQAPK1-H2VDNKFNKEHNFADQEIANLPNLNFYQKWAFIRSLMDDPSQSANLL AEAKKLNDAQAPK1-A4VDNKFNKEMEFADIEIQSLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-A6VDNKFNKETWFADSEIAQLPNLNFYQKWAFIRSLMDDPSQSANLL AEAKKLNDAQAPK1-B4VDNKFNKEETFADKEIAELPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-B6VDNKFNKEQEFADVEIATLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-C4VDNKFNKEEHFADIEIASLPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK1-C5VDNKFNKEFQFADREIAVLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-C6VDNKFNKEITFADSEIASLPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK1-D4VDNKFNKEMEFADQEIVVLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK1-D5VDNKFNKEKSFADNEIAELPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-E4VDNKFNKETHFADKEIANLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-E5VDNKFNKEEQFADMEIASLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK1-F4VDNKFNKEHSFADNEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-F5VDNKFNKEATFADLEIEALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-G3VDNKFNKEENFADNEIASLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-G4VDNKFNKESAFADIEIASLPNLNFYQKWAFIRKLMDDPSQSANLLAE AKKLNDAQAPK1-G5VDNKFNKEELFADQEIANLPNLNFYQKWAFMRSLMDDPSQSANLL AEAKKLNDAQAPK1-H3VDNKFNKEAVFADEEITNLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-H5VDNKFNKETLFADHEIANLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-A8VDNKFNKEKHFADEEIAKLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-B7VDNKFNKEERFADLEISVLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-B8VDNKFNKEMTFADYEISVLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-C7VDNKFNKEVQFADEEIAMLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK1-C8VDNKFNKEELFADEEIQALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-D6VDNKFNKEDKFADEEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-D7VDNKFNKEEHFADEEIASLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-D8VDNKFNKEERFADEEIASLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-E7VDNKFNKEYRFADTEIADLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-E8VDNKFNKEQSFADEEIAFLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-F8VDNKFNKEELFADTEIAQLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-G6VDNKFNKENQFADIEIAYLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-H6VDNKFNKEHFFADTEIAFLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-H7VDNKFNKEAVFADHEIAFLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-H8VDNKFNKENEFADEEIALLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-A9VDNKFNKEDDFADEEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-A10VDNKFNKETDFADVEIVALPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 1-C9VDNKFNKEERFADMEISNLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-C11VDNKFNKEEAFADTEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-D10VDNKFNKEETEADMEISNLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-D11VDNKFNKEQKFADDEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 1-E9VDNKFNKEEAFADMEIERLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK1-E10VDNKFNKEINFADEEIAYLPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK1-H10VDNKFNKEEQFADQEIALLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 2-B2VDNKFNKEHAFADQEIAILPNLNFYQKWAFIRSLVDDPSQSANLLAE AKKLNDAQAPK1-B12VDNKFNKEDTFADNEIAFLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK2-D1VDNKFNKEQYFADYEIAHLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK1-D12VDNKFNKEEHFADLEISALPNLNFYQKWAFIRSLLDDPSQSANLLAE AKKLNDAQAPK1-F11VDNKFNKEISFADQEIATLPNLNFYQKWAFIRSLMDDPSQSANLLAE AKKLNDAQAPK2-G1VDNKFNKESNFADYEIAQLPNLNFYQKWAFIRKLIDDPSQSANLLAE AKKLNDAQAPK1-G11VDNKFNKEYDFADEEITALPNLNFYQKWAFIRKLLDDPSQSANLLAE AKKLNDAQAPK2-A4VDNKFNKEAQFADIEISFLPNLNFYQKWAFIRSLVDDPSQSANLLAE AKKLNDAQAPK 2-B3VDNKFNKEVDFADEEIAQLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK141 2-B4VDNKFNKEKEHADEEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 142 2-C3VDNKFNKEEWFADNEIAELPNLNFYQKWAFIRSLMDDPSQSANLL AEAKKLNDAQAPK 143 2-D4VDNKFNKEEQFADQEITNLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 144 2-E3VDNKFNKEESFADTEIANLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 145 2-G2VDNKFNKEDVEADKEIAQLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK 146 2-G3VDNKFNKERYYADVEIAKLPNLNFFQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 147 2-H4VDNKFNKENEFADEEIAELPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 148 2-A5VDNKFNKEQFQADMEIAQLPNLNFYQKWAFIRSLMDDPSQSANLL AEAKKLNDAQAPK 149 2-A6VDNKFNKEFAFADEEIAQLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 150 2-B7VDNKFNKEYKFADVEITDLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 151 2-D6VDNKFNKEFQADMEISHLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 152 2-F6VDNKFNKEEETADMEIARLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 153 2-D9VDNKFNKEKQQADEEIAHLPNLNFYQKWAFIRSLMDDPSQSANLL AEAKKLNDAQAPK 154 2-H8GDNKFNKEDQFADTEIAALPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 155 2-E10VDNKFNKEVRFADTEIAYLPNLNFYQKWAFIRSLMDDPSQSANLLA EAKKLNDAQAPK 156 2-H10VDNKFNKEDMFADMEIATLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK 157 2-C11VDNKFNKEQSFADEEIAILPNLNFYQKWAFVRSLMDDPSQSANLLA EAKKLNDAQAPK 158 2-G12VDNKFNKEEQYADVEIAYLPNLNFYQKWAFIRKLMDDPSQSANLLA EAKKLNDAQAPK 159 2-F11VDNKFNKEESFADWEIQKLPNLNFYQKWAFIRKLMDDPSQSANLL AEAKKLNDAQAPK In another very preferred embodiment, the hBCMA-binding polypeptide is apolypeptide comprising a sequence selected from the group consisting of SEQ ID NO:32 to 38 (Example ID 1036 to 1042 of Figure 5 and a sequence of Table 4 below, or aderivative thereof (for example wherein from 1 to 5 (for example 1, 2 or 3) aminoacid residues are replaced by an alternative residue, for example a different naturally occurring amino acid or a different unnatural amino acid; or a different naturally occurring amino acid excluding methionine or a different unnatural amino acid). Table 4: hBCMA-binding motif sequences SEQ ID NO: Sequence160 ETFADLEISNLPNLNFYQKWAFIRSLM161 NQFADEEIAALPNLNFYQKWAFIRKLM162 EIFADREIAFLPNLNFYQKWAFIRKLM163 SQFADEEIEALPNLNFYQKWAFIRSLM164 QEFADYEIATLPNLNFYQKWAFIRSLM165 DSFADTEIAKLPNLNFYQKWAFIRSLM166 EIFADQEIEALPNLNFYQKWAFIRSLM167 DYFADYEIATLPNLNFYQKWAFIRSLM168 EQFADEEIAHLPNLNFYQKWAFIRSLM169 SMFADIEITKLPNLNFYQKWAFIRKLM170 EVFADEEIASLPNLNFYQKWAFIRSLM171 VREADEEIAALPNLNFYQKWAFIRKLM172 HQFADYEIAMLPNLNFYQKWAFIRSLM173 HFFADKEIAKLPNLNFYQKWAFIRSLM174 KAFADTEIVNLPNLNFYQKWAFIRSLM175 SEFADAEIANLPNLNFYQKWAFIRKLM176 ENFADHEIALLPNLNFYQKWAFIRKLM177 DSHADEEIAALPNLNFYQKWAFIRKLM178 SKFADEEIAKLPNLNFYQKWAFIRSLM179 QQFADEEIAMLPNLNFYQKWAFIRKLM180 HHFADIEISHLPNLNFYQKWAFIRSLM181 SQFADQEIAALPNLNFYQKWAFIRKLM182 EYFADSEIAQLPNLNFYQKWAFIRKLM183 EKFADVEIAYLPNLNFYQKWAFIRKLM184 TEFADSEIVRLPNLNFYQKWAFIRSLM185 TTFADQEIASLPNLNFYQKWAFIRKLM186 YKFADYEIVALPNLNFYQKWAFIRKLM187 FQFADIEIAELPNLNFYQKWAFIRSLM188 QTFADQEIAELPNLNFYQKWAFIRKLM189 TSFADKEIALLPNLNFYQKWAFIRKLM190 RMFADIEIQQLPNLNFYQKWAFIRSLM191 IMFADQEIVSLPNLNFYQKWAFIRSLM192 TQFADQEIAFLPNLNFYQKWAFIRKLM193 LDFADQEIAYLPNLNFYQKWAFIRSLM194 LIFADEEIVALPNLNFYQKWAFIRSLM195 HFFADSEIAALPNLNFYQKWAFVRSLM196 HNFADQEIANLPNLNFYQKWAFIRSLMMEFADIEIQSLPNLNFYQKWAFIRSLMTWFADSEIAQLPNLNFYQKWAFIRSLMETFADKEIAELPNLNFYQKWAFIRKLMQEFADVEIATLPNLNFYQKWAFIRKLMEHFADIEIAS LPNLNFYQKWAFIRSLMFQFADREIAVLPNLNFYQKWAFIRSLMITFADSEIASLPNLNFYQKWAFIRSLMMEFADQEIVVLPNLNFYQKWAFIRKLMKSFADNEIAELPNLNFYQKWAFIRKLMTHFADKEIANLPNLNFYQKWAFIRSLMEQFADMEIASLPNLNFYQKWAFIRKLMHSFADNEIAALPNLNFYQKWAFIRSLMATFADLEIEALPNLNFYQKWAFIRKLMENFADNEIASLPNLNFYQKWAFIRSLMSAFADIEIASLPNLNFYQKWAFIRKLMELFADQEIANLPNLNFYQKWAFMRSLMAVFADEEITNLPNLNFYQKWAFIRSLMTLFADHEIANLPNLNFYQKWAFIRSLMKHFADEEIAKLPNLNFYQKWAFIRKLMERFADLEISVLPNLNFYQKWAFIRKLMMTFADYEISVLPNLNFYQKWAFIRSLMVQFADEEIAMLPNLNFYQKWAFIRKLMELFADEEIQALPNLNFYQKWAFIRSLMDKFADEEIAALPNLNFYQKWAFIRSLMEHFADEEIASLPNLNFYQKWAFIRKLMERFADEEIASLPNLNFYQKWAFIRKLMYRFADTEIADLPNLNFYQKWAFIRKLMQSFADEEIAFLPNLNFYQKWAFIRSLMELFADTEIAQLPNLNFYQKWAFIRSLMNQFADIEIAYLPNLNFYQKWAFIRSLMHFFADTEIAFLPNLNFYQKWAFIRKLMAVFADHEIAFLPNLNFYQKWAFIRKLMNEFADEEIALLPNLNFYQKWAFIRSLMDDFADEEIAALPNLNFYQKWAFIRSLMTDFADVEIVALPNLNFYQKWAFIRKLMERFADMEISNLPNLNFYQKWAFIRSLMEAFADTEIAALPNLNFYQKWAFIRSLMETEADMEISNLPNLNFYQKWAFIRSLMQKFADDEIAALPNLNFYQKWAFIRSLMEAFADMEIERLPNLNFYQKWAFIRSLMINFADEEIAYLPNLNFYQKWAFIRSLMEQFADQEIALLPNLNFYQKWAFIRKLM239 HAFADQEIAILPNLNFYQKWAFIRSLV240 DTFADNEIAFLPNLNFYQKWAFIRSLM241 QYFADYEIAHLPNLNFYQKWAFIRKLM242 EHFADLEISALPNLNFYQKWAFIRSLL243 ISFADQEIATLPNLNFYQKWAFIRSLM244 SNFADYEIAQLPNLNFYQKWAFIRKLI245 YDFADEEITALPNLNFYQKWAFIRKLL246 AQFADIEISFLPNLNFYQKWAFIRSLV247 VDFADEEIAQLPNLNFYQKWAFIRSLM248 KEHADEEIAALPNLNFYQKWAFIRSLM249 EWFADNEIAELPNLNFYQKWAFIRSLM250 EQFADQEITNLPNLNFYQKWAFIRSLM251 ESFADTEIANLPNLNFYQKWAFIRSLM252 DVEADKEIAQLPNLNFYQKWAFIRKLM253 RYYADVEIAKLPNLNFFQKWAFIRKLM254 NEFADEEIAELPNLNFYQKWAFIRSLM255 QFQADMEIAQLPNLNFYQKWAFIRSLM256 FAFADEEIAQLPNLNFYQKWAFIRSLM257 YKFADVEITDLPNLNFYQKWAFIRSLM258 EETADMEIARLPNLNFYQKWAFIRSLM259 KQQADEEIAHLPNLNFYQKWAFIRSLM260 DQFADTEIAALPNLNFYQKWAFIRSLM261 VRFADTEIAYLPNLNFYQKWAFIRSLM262 DMFADMEIATLPNLNFYQKWAFIRKLM263 QSFADEEIAILPNLNFYQKWAFVRSLM264 EQYADVEIAYLPNLNFYQKWAFIRKLM265 ESFADWEIQKLPNLNFYQKWAFIRKLMCD16a binder-drug conjugatesAlternatively or additionally, a CD16a-binding polypeptide or CD16a-bindingoligomer as disclosed herein may be attached to a therapeutic agent to form aCD16a binder-drug conjugate. Therefore, in an embodiment, the at least one CD16a-binding polypeptide or CD16a-binding oligomer is typically covalently attached to one or more therapeutic agent(s), optionally via a linker or linkers, for example alinker or linkers as described above. Non-limiting examples of such therapeuticagents include cytotoxic drugs, for example mitomycin C, desmethyltopotecan, SN- 38, MMAE, MMAF, doxorubicin, pyrrolobenzodiazepine, amanitin, maytansinoids (for example maytansinoid DM1 or maytansinoid DM4), or duostatins (for example duostatin 5.2). For the avoidance of doubt, during the generation of a CD16a binder-drug conjugate according to the invention, the one or more therapeutic agent(s) (for example MMAF) is necessarily modified by the reaction between the functional group at the point of attachment (for example –NH, –OH or –SH (for example in a Cys)) and any attachment groups or linkers used. The skilled person will therefore understand thatthe therapeutic agent in a CD16a binder-drug conjugate (for example a CD16abinder-MMAF conjugate) comprises such a modification.Polypeptide-oligonucleotide conjugatesAlternatively or additionally, a CD16a binding polypeptide or CD16a-binding oligomeras disclosed herein may be attached to an oligonucleotide. The oligonucleotide canbe a single- or double-stranded DNA, RNA or PNA molecule. The function of theoligonucleotide could be as a messenger, antisense, interference or guide to be usedfor gene expression regulation or specific gene editing purposes.Polypeptide productionThe polypeptides and oligomers of the invention can be manufactured usingmethods known in the art. For example, they can be prepared by chemical synthesismethods or by recombinant protein production techniques in, for example, bacterial,yeast, insect, fungal, plant or mammalian cells. Synthetic linkers of the presentinvention may be synthesised according to methods known in the art, for example asdescribed in Bird, R. E., et al, Bioconjugate Chem, 2021, 32, 2457–2479; Forte, N., etal, DDTEC 2018, 562; Neumann, S., et al, Marcomol. Rapid Commun. 2020, 41,1900359; and Blackman, M. L., et al, J. Am. Chem. Soc. 2008, 130, 13518-13519.Polypeptides and oligomers of the invention may also be fused, via recombinant or chemical synthesis techniques as described above, to a different molecule with therapeutic potential, for example an immunoglobulin with therapeutic potential. Derivatives, Salts and Solvates The present invention provides polypeptides and oligomers, derivatives of such polypeptides and oligomers, and salts or solvates of such polypeptides and oligomers and derivatives thereof.Whilst in some embodiments, the invention relates to a polypeptide or oligomer ofthe invention and is not a derivative, in other embodiments the invention relates toa derivative of a polypeptide and oligomer of the invention. The derivative may forexample comprise one or more derivatisations selected from amidation and / oracylation.In certain embodiments it is preferred that the polypeptides and oligomers of theinvention may be amidated at their C-terminal. Such a modification is very commonin nature with approximately half of naturally occurring peptides being susceptible toamidation at their C-terminal. The present invention encompasses all of the genericand specific sequences disclosed herein, including in the sequence listing anddrawings and examples, in both amidated and non-amidated forms, the amidationwhere present being especially preferred on the C-terminal of the peptide sequence.In certain embodiments it is preferred that the polypeptides and oligomers of theinvention may be acylated at their N-terminal. The present invention encompassesall of the generic and specific sequences disclosed herein, including in the sequencelisting and drawings and examples, in both acylated and non-acylated forms, theacylation where present being especially preferred on the N-terminal of the peptidesequence. Salt forms of the polypeptides and oligomers of the invention, and of derivatives of such polypeptides and oligomers, also form part of the invention. In someembodiments the salt is a salt of a polypeptide or oligomer of the invention. In otherembodiments the salt is a salt of a derivative of a polypeptide or oligomer of the invention.Salts of polypeptides or oligomers of the invention include those which arepharmaceutically acceptable, i.e. which are suitable for use in medicine. However, salts having non-pharmaceutically acceptable counterions are also within the scope of the present invention, for example, for use as intermediates in the preparation ofthe polypeptides or oligomers of the invention.Suitable salts according to the invention include those formed with organic or inorganic acids or bases. Pharmaceutically acceptable acid addition salts include those formed with hydrochloric, hydrobromic, sulphuric, nitric, citric, tartaric, acetic, phosphoric, lactic, pyruvic, acetic, trifluoroacetic, succinic, perchloric, fumaric, maleic, glycolic, salicylic, oxaloacetic, methanesulfonic, ethanesulfonic, p- toluenesulfonic, formic, benzoic, malonic, naphthalene-2-sulfonic, benzenesulfonic, and isethionic acids. Other acids such as oxalic acid may be useful as intermediates in obtaining the compounds of the invention in final form. Pharmaceutically acceptable salts with bases include ammonium salts, alkali metal salts, for example potassium and sodium salts, alkaline earth metal salts, for example calcium and magnesium salts, and salts with organic bases, for example dicyclohexylamine and N-methyl-D-glucomine. More preferably, the salt of a polypeptide, oligomer or derivative of the present invention is the hydrochloride salt, trifluoroacetate salt or acetate salt (i.e. theaddition salt formed from hydrochloric acid, trifluoroacetic acid or acetic acid). Morepreferably, the salt is the acetate salt. Those skilled in the art of organic and / or medicinal chemistry will appreciate that many organic compounds can form complexes with solvents in which they are reacted or from which they are precipitated or crystallized. Such complexes are known as "solvates". For example, a complex with water is known as a "hydrate". The invention also encompasses solvates of the polypeptides and oligomers of the present invention, solvates of derivatives of the polypeptides and oligomers of the present invention, and solvates of salts of the derivatives. Those skilled in the art of organic and / or medicinal chemistry will also appreciatethat many organic compounds can exist in different forms, including as amorphousmaterial and / or in one or more crystalline forms. Different physical forms of organic compounds are known as polymorphs. The invention also encompasses all such different physical forms of the polypeptides and derivatives of the invention, as well as different physical forms of their derivatives and salts.Modulation of polypeptide propertiesThe pharmacokinetic properties of the polypeptides of the invention can bemodulated by methods known in the art. For example, they can be linked to amoiety extending the plasma half-life, such as a polyethylene glycol polymer, anunstructured polypeptide (such as XTEN or PAS), or an FcRn-binding ligand such asserum albumin or the Fc domain of an immunoglobulin. FormulationsPolypeptides according to the invention (for example, a CD16a-binding polypeptideor CD16a-binding oligomer of the present invention, or a CD16a binder-drugconjugate) may be present in a formulation and particularly in a pharmaceuticalformulation. In certain embodiments, the invention provides a nucleic acid molecule encoding the CD16a-binding polypeptide or CD16a-binding oligomer of the invention. Such a nucleic acid molecule encoding the CD16a-binding polypeptide or CD16a-bindingoligomer of the invention may be used as a medicament, for example may be usedfor the treatment of cancer. The nucleic acid molecule may, for example, be a DNAor an RNA molecule, for example a mRNA molecule. Nucleic acid molecules according to the invention may be present in a formulation and particularly in a pharmaceutical formulation. As such, the present invention further provides aformulation and particularly a pharmaceutical formulation of a nucleic acid molecule(for example, a DNA or RNA, and in particular a mRNA molecule) encoding the CD16a-binding polypeptide or CD16a-binding oligomer of the invention.Pharmaceutical formulations include for example those suitable for oral, parenteral(including subcutaneous, intradermal, intraosseous infusion, intramuscular,intravascular (bolus or infusion), and intramedullary), or intraperitonealadministration, although the most suitable route may depend upon, for example, thecondition and disorder of the subject under treatment. In one embodiment of the invention, a CD16a-binding polypeptide or CD16a-binding oligomer (in particular a CD16a binder-drug conjugate) or nucleic acids (for example DNA or RNA molecules of the present invention, for example an mRNA molecule) according to the invention is administered as a pharmaceutical formulation suitable for oral or parenteral (including subcutaneous, intradermal, intraosseous infusion, intramuscular, intravascular (bolus or infusion), and intramedullary) administration. Pharmaceutical formulations suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. Peptides of the invention may also be presented as a bolus, electuary or paste. Various pharmaceutically acceptable carriers and their formulation are described in standard formulation treatises, e.g., Remington's Pharmaceutical Sciences by E. W. Martin. See also Wang, Y. J. and Hanson, M. A., Journal of Parenteral Science and Technology, Technical Report No. 10, Supp.42:2S, 1988. Formulations for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may includesuspending agents and thickening agents. Preferably, the formulations may bepresented in unit dosage or divided dosage containers, for example sealed ampoules and vials. The formulation may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example saline, a physiologically acceptable solution or water-for-injection, immediately prior to use. Extemporaneous injection and infusion solutions and suspensions may be prepared from sterile powders, granules or other dry compositions. Exemplary compositions for parenteral administration include injectable solutions or suspensions which can contain, for example, suitable non-toxic, parenterally acceptable diluents or solvents,such as mannitol, 1,3-butanediol, water, Ringer’s solution, an isotonic sodiumchloride solution, or other suitable dispersing or wetting and suspending agents,including synthetic mono- or diglycerides, and fatty acids, including oleic acid, orCremaphor.Dosage regimensA CD16a-binding polypeptide or CD16a-binding oligomer (in particular a CD16abinder-drug conjugate) of the invention, and a pharmaceutical formulationcomprising such a polypeptide, oligomer or binder-drug conjugate, or nucleic acid molecules of the invention (for example, DNA or RNA molecules of the present invention, for example a mRNA molecule of the present invention), andpharmaceutical formulations comprising those nucleic acid molecules, find use in thetreatment and / or prophylaxis of cancer, for example multiple myeloma.The amount of a CD16a-binding polypeptide or CD16a-binding oligomer (in particulara CD16a binder-drug conjugate) or nucleic acid molecule, required to achieve atherapeutic effect will vary with the particular route of administration and thecharacteristics of the subject under treatment, for example the species, age, weight, sex, medical conditions, the particular disease and its severity, and other relevant medical and physical factors. An ordinarily skilled physician can readily determine and administer the effective amount of the CD16a-binding polypeptide, CD16a-binding oligomer, CD16a binder-drug conjugate and / or composition comprising thesame, or nucleic acid molecule and / or composition comprising the same, required for treatment and / or prophylaxis of cancer. A CD16a-binding polypeptide, CD16a-binding oligomer (in particular a CD16a binder- drug conjugate) or nucleic acid molecule of the invention, or a pharmaceutical formulation thereof, may for example be administered daily, weekly, every second, third or fourth week or even as a high single dose depending on the subject and severity of the cancer to be treated.A CD16a-binding polypeptide, CD16a-binding oligomer (in particular a CD16a binder-drug conjugate) or nucleic acid molecule of the invention, or a pharmaceutical formulation thereof, may for example be administered as a parenteral or oral dosage. Parenteral administration includes intravenous (into a vein, for example a central or a peripheral vein, bolus or infusion), intra-arterial (into an artery, for example a central or a peripheral artery), intraosseous infusion (into the bone marrow), intra-muscular (into muscle), intradermal (into the dermis), and subcutaneous (under the skin) administration. In one preferred embodiment, the dosage of the present invention is administered intravenously or intra-arterially, and more preferably by intravenous infusion (for example central intravenous infusion or peripheral intravenous infusion). In another preferred embodiment, the dosage of the present invention is administered by subcutaneous injection. As such, pharmaceutical formulations especially useful for the present invention are those suitable for intravenous administration, more especially intravenous infusion, or subcutaneous administration. A CD16a-binding polypeptide, CD16a-binding oligomer (in particular a CD16a binder- drug conjugate) or nucleic acid molecule of the invention, and pharmaceuticalformulations thereof, may be administered as part of a treatment cycle. In atreatment cycle, said polypeptides may be administered on day 1 of the cycle,wherein the cycle lasts X days, with no further administration of the CD16a-bindingpolypeptides or CD16a-binding oligomers of the invention for the next X-1 days. Xmay be, for example, from 1 to 42, for example from 2 to 14 days. Alternatively, theCD16a-binding polypeptides or CD16a-binding oligomers may be administered as asplit dose, for example on for example on days 1 and 2 of the cycle. The cycle may be repeated one or several times depending on the category, class or stage of the cancer to be treated. For example, the cycle may be repeated from 1 to100 times, for example from 2 to 50 times, for example 8 to 40 times, for example 8or 16 times. For example, the CD16a-binding polypeptides or CD16a-bindingoligomers or nucleic acid molecules of the invention may be administered for 8repeats of a 7 day cycle, followed by 16 repeats of a 14 day cycle, optionally followedby further repeats of a 28 day cycle. An ordinarily skilled physician or clinician can readily determine the number of cycles of CD16a-binding polypeptide (for example CD16a binder-drug conjugate) required to prevent, counter or arrest the progress of the cancer. Combination treatments Whilst a CD16a-binding polypeptide or CD16a-binding oligomer (in particular a CD16a binder-drug conjugate) or nucleic acid molecules disclosed herein may be used as the sole active ingredient in the present invention, it is also possible for it to be used in combination with one or more further therapeutic agent(s), and the use of such combinations provides one embodiment of the invention. Such further therapeutic agents may be agents useful in the treatment and / or prophylaxis of cancer, or other pharmaceutically active materials. Such agents are known in the art. Non-limiting examples of further therapeutic agents for use in the present inventionmay include proteasome inhibitors (PIs) (for example carfilzomib, bortezomib orixazomib), immunomodulatory agents (IMiDs) (for example lenalidomide,thalidomide or pomalidomide), alkylators (for example cyclophosphamide,melphalan, bendamustine or melflufen), anthracyclines (for example doxorubicin),steroids (for example dexamethasone, prednisone or prednisolone), BCL-2 inhibitors(for example venetoclax), histone deacetylase (HDAC) inhibitors (for example panobinostat), anti-CD38 agents (for example daratumumab or isatuximab), immune checkpoint inhibitors (for example a CTLA-4 inhibitor, a PD-1 inhibitor, or a PD-L1inhibitor), or ADAM17 inhibitors. For example, further therapeutic agents may beselected from proteasome inhibitors (for example carfilzomib or bortezomib), immunomodulatory agents (for example lenalidomide or thalidomide), alkylators(for example melphalan or melfufen), steroids (for example dexamethasone orprednisone), anti-CD38 agents (for example daratumumab), an immune checkpoint inhibitor (for example a CTLA-4 inhibitor, a PD-1 inhibitor, or a PD-L1 inhibitor), and an ADAM17 inhibitor. The one or more further therapeutic agent(s) may be used simultaneously, sequentially or separately with / from the administration of the dosage of CD16a- binding polypeptides, CD16a-binding oligomers, CD16a binder-drug conjugates, or nucleic acid molecules of the invention. The individual components of such combinations can be administered separately at different times during the course oftherapy, or concurrently in divided or single combination forms. In an embodiment of the invention, the one or more further therapeutic agent(s) are selected from a PI, an IMiD, and a steroid. For example, the one or more further therapeutic agents are a PI (for example bortezomib or carfilzomib), an IMiD (forexample lenalidomide, thalidomide or pomalidomide), and / or a steroid (for example,prednisone, prednisolone or dexamethasone). Preferably, the one or moretherapeutic agents are bortezomib, thalidomide, and / or dexamethasone.In an embodiment of the invention, the one or more further therapeutic agent(s) are selected from a PI, an alkylator, and a steroid. For example, the one or more further therapeutic agents are a PI (for example bortezomib or carfilzomib), an alkylator (forexample cyclophosphamide, melphalan, melflufen or bendamustine), and / or asteroid (for example, prednisone, prednisolone and dexamethasone). Preferably, the one or more therapeutic agents are bortezomib, melphalan, melflufen, and / or prednisone. In an embodiment of the invention, the one or more further therapeutic agent(s) are selected from a PI and a steroid. For example, the one or more therapeutic agentsare a PI (for example bortezomib or carfilzomib), and / or a steroid (for example,prednisone, prednisolone or dexamethasone). Preferably, the PI is bortezomib andthe steroid is dexamethasone.In an embodiment of the invention, the one or more further therapeutic agent(s) are selected from an IMiD and a steroid. For example, the one or more therapeuticagents are an IMiD (for example lenalidomide, thalidomide or pomalidomide),and / or a steroid (for example, prednisone, prednisolone or dexamethasone).Preferably, the IMiD is lenalidomide and the steroid is dexamethasone. In another embodiment of the invention, the one or more therapeutic agent(s) may be selected from an NK cell-based or T cell-based therapy. Alternatively, a CD16a-binding polypeptide or CD16a-binding oligomer (in particulara CD16a binder-drug conjugate) or nucleic acid molecule according to the inventionmay be combined with a therapeutic procedure such as a stem cell transplantation procedure, for example an autologous stem cell transplant or an allogenic stem cell transplant. Therefore, in an embodiment of the invention, a CD16a-binding polypeptide disclosed herein may be combined with an autologous stem cell transplantation procedure. In another embodiment of the invention, a CD16a-binding polypeptide disclosed herein may be combined with an allogenic stem celltransplantation procedure. The simultaneous, sequential or separate administration of one or more further therapeutic agent(s) or therapeutic procedure with the CD16a-binding polypeptides, CD16a-binding oligomers, CD16a binder-drug conjugates or nucleic acid molecules of the invention further enhances their effectiveness in the treatment and / or prophylaxis of cancer. Kits The present invention provides a kit comprising a CD16a-binding polypeptide, CD16a-binding oligomer (in particular a CD16a binder-drug conjugate) or nucleic acid molecule as disclosed herein, and one or more further therapeutic agents that are useful in the treatment and / or prophylaxis of cancer. Non-limiting examples of further therapeutic agents for use in a kit of the presentinvention may include proteasome inhibitors (PIs) (for example carfilzomib,bortezomib or ixazomib), immunomodulatory agents (IMiDs) (for example lenalidomide, thalidomide or pomalidomide), alkylators (for examplecyclophosphamide, melphalan, melflufen or bendamustine), anthracyclines (forexample doxorubicin), steroids (for example dexamethasone, prednisone or prednisolone), BCL-2 inhibitors (for example venetoclax), histone deacetylase (HDAC) inhibitors (for example panobinostat), anti-CD38 agents (for example daratumumab or isatuximab), immune checkpoint inhibitors (for example a CTLA-4 inhibitor, a PD-1inhibitor, or a PD-L1 inhibitor), or ADAM17 inhibitors. The one or more furthertherapeutic agents may for example be selected from proteasome inhibitors (forexample carfilzomib or bortezomib), immunomodulatory agents (for examplelenalidomide or thalidomide), alkylators (for example melphalan or melflufen),steroids (for example dexamethasone or prednisone), anti-CD38 agents (for example daratumumab), an immune checkpoint inhibitor (for example a CTLA-4 inhibitor, a PD-1 inhibitor, or a PD-L1 inhibitor), and an ADAM17 inhibitor. In one embodiment of the invention, the kit of the present invention finds use in thetreatment and / or prophylaxis of cancer.For the avoidance of doubt, a CD16a-binding polypeptide, CD16a-binding oligomer(in particular a CD16a binder-drug conjugate) or nucleic acid molecule as disclosedherein is present in a kit according to the present invention in a form and quantity suitable for use according to the present invention. Suitable pharmaceutical formulations are described herein. The skilled person can readily determine a quantity of the CD16a-binding polypeptide or oligomer (for example in the form of a CD16a binder-drug conjugate) or nucleic acid molecule as disclosed herein suitable for the use according to the present invention. CancersCD16a-binding polypeptides or CD16a-binding oligomers of the present invention (inparticular CD16a binder-drug conjugates), or nucleic acid molecules of the presentinvention, as well as pharmaceutical formulations or kits of the present invention comprising said CD16a-binding polypeptides, CD16a-binding oligomers, CD16abinder-drug conjugates or nucleic acid molecules, find use in medicine, for examplein the treatment and / or prophylaxis of cancer in a subject. Non-limiting examples ofcancers include: solid cancers, such as bladder cancer, breast cancer, colorectalcancer, CNS cancers, endometrial cancer, kidney cancer, liver cancer, lung cancer, skin cancer, ovarian pancreatic cancer, prostate cancer, or thyroid cancer; and blood cancers, such as leukaemias (for example acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia, or chronic lymphocytic leukaemia), lymphomas (for example Hodgkin lymphoma, non-Hodgkin lymphoma,cutaneous T-cell lymphoma, small lymphocytic lymphoma, and other high-grade B-cell lymphomas), or plasma cell neoplasms and myelomas (for example, MGUS,plasmacytoma, smouldering myeloma, multiple myeloma, light chain myeloma, or non-secretory myeloma). Preferably, CD16a-binding polypeptides or CD16a-binding oligomers of the present invention (in particular CD16a binder-drug conjugates) or nucleic acid molecules of the present invention, as well as pharmaceutical formulations or kits of the present invention comprising said CD16a-binding polypeptides, oligomers, binder-drugconjugates or nucleic acid molecules, find use in the treatment and / or prophylaxis ofblood cancers, such as leukaemias (for example acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia, or chronic lymphocytic leukaemia), lymphomas (for example Hodgkin lymphoma, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, small lymphocytic lymphoma, and other high-grade B- cell lymphomas), or plasma cell neoplasms and myelomas (for example, MGUS, plasmacytoma, smouldering myeloma, multiple myeloma, light chain myeloma, ornon-secretory myeloma). Preferably, CD16a-binding polypeptides or CD16a-bindingoligomers of the present invention, as well as pharmaceutical formulations or kits ofthe present invention comprising said CD16a-binding polypeptides or CD16a-bindingoligomers, find use in the treatment and / or prophylaxis of myelomas (for example,MGUS, plasmacytoma, smouldering myeloma, multiple myeloma, light chainmyeloma, or non-secretory myeloma). Most preferably, CD16a-binding polypeptides,CD16a-binding oligomers, CD16a binder-drug conjugates or nucleic acid molecules of the present invention, as well as pharmaceutical formulations or kits of the present invention comprising said CD16a-binding polypeptides, CD16a-binding oligomers, CD16a binder-drug conjugates or nucleic acid molecules, find use in the treatment and / or prophylaxis of multiple myeloma. In certain embodiments the CD16a-binding polypeptides or CD16a-binding oligomers of the present invention (in particular CD16a binder-drug conjugates) or nucleic acid molecules of the present invention, as well as pharmaceutical formulations or kits of the present invention comprising said CD16a-binding polypeptides, oligomers, binder-drug conjugates or nucleic acid molecules, find use as anti-cancer immunotherapeutics; for example anti-cancer immunotherapeutics for use in the treatment of cancers, and in particular blood cancers, for example a blood cancer as described herein, and in particular multiple myeloma. Alternatively or additionally, polypeptides or nucleic acid molecules of the present invention, as well as pharmaceutical formulations or kits of the present inventioncomprising a hBCMA-binding polypeptide, hBCMA-binding oligomer, hBCMA binder-drug conjugate or nucleic acid molecules, may also find use in the treatment and / or prophylaxis of an autoimmune disorder in a subject. Non-limiting examples of autoimmune disorders include Addison’s disease, coeliac disease, dermatomyositis, Graves disease, Hashimoto’s thyroiditis, multiple sclerosis and optic neuritis, myasthenia gravis, pernicious anemia, reactive arthritis or rheumatoid arthritis, Sjögren’s syndrome, systemic lupus erythematosus, or Type I diabetes, in particular autoimmune disorders in which hBCMA signalling is implicated, for example systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and optic neuritis and Sjögren’s syndrome. Whilst the present invention has been described and illustrated with reference to particular embodiments, it will be appreciated by those of ordinary skill in the art that the invention lends itself to many different variations not specifically illustrated herein. Where in the foregoing description, integers or elements are mentioned which have known, obvious or foreseeable equivalents, then such equivalents are herein incorporated as if individually set forth. Reference should be made to the claims for determining the true scope of the present invention, which should be construed so as to encompass any such equivalents. It will also be appreciated by the reader that integers or features of the invention that are described as preferable, advantageous, convenient or the like are optional and do not limit the scope of the independent claims. Moreover, it is to be understood that such optional integers or features, whilst of possible benefit in some embodiments of the invention, may not be desirable, and may therefore be absent, in other embodiments.

[0003] Examples The following Examples illustrate the invention.Preparative Example 1:Synthesis of heterotrimeric hBCMA × hCD16a dual engagers of the invention (Q1 andQ2) CD16a-binding polypeptides of the present invention that are heterotrimeric hBCMA× hCD16a dual engagers having the sequences shown in Table 5 below (‘Q1’ and‘Q2’) were expressed as soluble gene products in E. coli (DE3).The cDNA coding for each hBCMA × hCD16a dual engager harbouring a stop codonwas synthesized and ligated into the Nde1 Xho1 restriction sites of the pET29 vector.E. coli BL21(DE3) was transformed with vector under Kanamycin selection andconstructs were expressed by induction of IPTG at an OD of 0.6 and harvested 16hlater. The cell pellet was resuspended in 1 x PBS and sonicated for 3 minutes withintervals of 30 seconds on and 30 seconds off. The sonicated cell lysate was heat-denatured at 96°C for 6 min and cooled down on ice for 5 min. The supernatant wascollected by centrifugation at 13,000 rpm for 10 min. Further purification was achieved by RP-HPLC and identity / purity was confirmed by SDS-PAGE and analysis by LC-MS / MS. Table 5 Example SEQ ID CD16a binder Sequence Compound NO:SEQ ID NO:Q1 SEQ ID SEQ ID NO: 2 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDNO: 5PSQSANLLAEAKKLNDAQAPKGGGSGGGGSGVDNKF NKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSA NLLAEAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQ QIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEA KKLNDAQAPK Q2 SEQ ID SEQ ID NO: 3 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDNO: 6PSQSANLLAEAKKLNDAQAPKGGGSGGGGSGVDNKF NKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSA NLLAEAKKLNDAQAPKGGGSGGGGSGVDNKFNKEQ QIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEA KKLNDAQAPK Biological Example 2:CD16a activation by heterotrimeric hBCMA × hCD16a dual engagers of PreparativeExample 1The functionality of the CD16a polypeptides of the invention synthesised inPreparative Example 1 (Q1 & Q2; SEQ ID NO: 5 and SEQ ID NO: 6), which areheterotrimeric hBCMA × hCD16a dual engagers, were assessed in a cell based CD16activation Jurkat-Lucia™ Luciferase reporter assay.CD16 activation Jurkat-Lucia™ Luciferase reporter assayThe propensity of the hBCMA × hCD16a dual engagers to stimulate CD16 activationwas assessed in a Lucia Luciferase reporter assay and compared to the antibodydependent cellular cytotoxicity (ADCC) potency of Elotuzumab (clinical grade a- SLAMF7 monoclonal antibody) through evaluation of CD16a activation. Jurkat-Lucia™NFAT-CD16 cells (effector cells; InvivoGen) were seeded with MM.1S cells (targetcells) at an effector to target (E:T) ratio of 2:1 in a 96-well flat-bottom plate (Assaysetup A) or 384-well flat-bottom plate (Assay setup B). In total, 3x105cells in 200 μl per well were treated with 20 or 200 nM of the engager of interest for 24h. Alternatively, the seeded cells were treated with 10 concentrations in the range 0.002–100 nM, using in total 3x105cells in 200 μl per well (Assay setup A) or with 11 concentrations in the range 0.002-200 nM, using in total 0.9x105cells in 30 µL per well (Assay setup B). The supernatant was harvested, and Lucia luciferase activity,which reflects the induced ADCC response, was assessed using QUANTI Luc™ Gold(InvivoGen™). Responses were normalized to the maximal response of Elotuzumab.ResultsThe results are shown in Tables 6 and 7 below, and in Figure 2. From Tables 6 and 7and Figure 2 it can be seen that the hBCMA × hCD16a dual engagers of the presentinvention (i.e. Q1 & Q2, SEQ ID NO: 5 and SEQ ID NO: 6), which are composed of thepolypeptides of SEQ ID NO: 4 (for hBCMA) and SEQ ID NO: 2 or SEQ ID NO: 3 (forhCD16a), induced CD16 activation in the Lucia Luciferase reporter assay in the presence of BCMA expressing MM.1S cells. Thus, the engagers of the present invention have been shown to have functional domains targeting both CD16a and BCMA.Table 6: hCD16a activation of the hBCMA × hCD16a dual engager trimeric syntheticconstructs, when tested at 2 different concentrationsausing Assay setup A. Example SEQ ID % activationn SD % activation at n SDCompound No at 20 nM 200 nM Q1 5 96.3 2 4.8 90.9 2 3.2Q2 6 90.2 7 6.5 97.9 7 8.0aNote: this table contains average values per dual engager (i.e. values from different batches of the dual engagers, different samples of the dual engagers and different assay occasions have been combined).Table 7: CD16a activation of the hBCMA × hCD16a dual engager trimeric syntheticconstructs, when tested at 10 concentrations using Assay setup A.ExampleSEQ ID No Mean EC50 (nM)Compound Q1 5 0.3917Q2 6 0.3283Biological Example 3 NK cell mediated cell killing by heterotrimeric hBCMA × hCD16a dual engagerssynthesised in Preparative Example 1The functionality of the CD16a polypeptides of the invention synthesised inPreparative Example 1 (Q1 & Q2, SEQ ID NO: 5 and SEQ ID NO: 6), which areheterotrimeric hBCMA × hCD16a dual engagers, were assessed in a cell killing assay.Calcein-release-based in vitro cytotoxicity assayNK cell cytotoxic activity was assessed in calcein-release-based cytotoxicity assay previously described by Gauthier et al, 2023 PMID 36635380. In brief, MM.1S target cells were pre-labelled with Calcein-AM (Biolegend) and co-cultured with NK cells at a 1:1 ratio in 96-well v-bottom plate. Engagers were added to the co-culture after seeding the effector cells and before seeding the target cells. After 4h of co-culture, supernatant was collected and transferred to black flat-bottom 96-well plate. Fluorescent signal of calcein-released by dead MM.1S cells was quantified in SpectraMax i3x (Molecular Devices). Percent specific lysis is calculated in Microsoft Excel (Microsoft) using target cells alone for spontaneous release as the minimum value and target cells with detergent for maximum release. ResultsThe results are shown in Table 8 below, and Figure 3. The results show that theheterotrimeric hBCMA × hCD16a dual engagers of the present invention activate hCD16a. The engagers induced NK cell mediated killing of MM.1S cells. A firm activation leading to NK mediated cell killing was seen for all engagers investigated. The heterotrimeric hBCMA × hCD16a dual engagers of the invention performed better than an anti-BCMA targeting multiple myeloma antibody (results not shown).Table 8: NK mediated cell killing of the heterotrimeric hBCMA × hCD16a dualengagers. ExampleSEQ ID NO: EC50 (nM) Top plateauCompound (%) Q1 SEQ ID NO: 5 0.03086 67.11Q2 SEQ ID NO: 6 0.03501 67.13 Biological Example 4 CD16a activation by a heterotrimeric hBCMA × hCD16a dual engager of theinvention is not inhibited by IgGThe functionality of a CD16a polypeptide of the present invention synthesised inPreparative Example 1 (Q1; SEQ ID NO: 5), which is a heterotrimeric hBCMA ×hCD16a dual engager, was assessed in a cell based CD16 activation Jurkat-Lucia™Luciferase reporter assay in the presence of IgG1 monoclonal antibody.CD16 activation Jurkat-Lucia™ Luciferase reporter assayThe propensity of the hBCMA × hCD16a dual engager to stimulate CD16 activation was assessed in a Lucia Luciferase reporter assay and compared to the antibody dependent cellular cytotoxicity (ADCC) potency of two different monoclonalantibodies: Elotuzumab (clinical grade anti-SLAMF7 monoclonal antibody) andBelantamab (research grade anti-BCMA monoclonal antibody). Jurkat-Lucia™ NFAT-CD16 cells (InvivoGen) were seeded with MM.1S cells at an effector to target (E:T) ratio of 2:1 in a 96-well flat-bottom plate.3x105cells in 200 μl per well were treated with 0, 2, 20 or 200 nM of the reagent of interest for 24h. Experiments were performed in the presence of 1mg / mL of either effector competent Trastuzumab(Clinical grade a-Her2 monoclonal antibody) or an effector free (LALAPG mutated) Fcsilent variant of Trastuzumab. Conditions without addition of IgG (‘vehicle’ condition) was also evaluated. The supernatant was harvested, and Lucia luciferase activity,which reflects the induced ADCC response, was assessed using QUANTI Luc™ Gold(InvivoGen). Responses were normalized to the maximal response of Elotuzumab. ResultsThe results are shown in Figure 6. It can be seen that the hBCMA × hCD16a dualengager of the present invention induced CD16 activation in the Lucia Luciferase reporter assay in the presence of BCMA expressing MM.1S cells. The activity was not affected by the presence of 1 mg / ml of the IgG antibody Trastuzumab. In contrast, both Elotuzumab and Belantamab activity was significantly inhibited by effector competent Trastuzumab. The effector free Trastuzumab did not impact activity of Elotuzumab or Belantamab, indicating that the inhibition is a direct consequence of competitive binding to the CD16 receptor. The lack of competitive binding with the Fc domain of any endogenous IgG, here represented by the IgG1 monoclonalTrastuzumab, is a beneficial feature of the present invention. The normal range ofIgG in human plasma ranges from 4-30 mg / mL and these natural concentrations are therefore assumed to dampen the specific response of a therapeutic monoclonalantibody against a tumour associated target. It is also documented that certaincancer forms can express IgG and thereby reduce ADCC potential of therapeuticmonoclonal antibodies (Front Immunol. 2021 Mar 24;12:613530. doi:10.3389 / fimmu.2021.613530). This obstacle associated with monoclonal antibody therapy is circumvented by the present invention. Biological Example 5:In vivo tumor growth inhibition by a heterotrimeric hBCMA × hCD16a dual engagerof the invention in a mouse model of multiple myelomaThe activity of a heterotrimeric hBCMA × hCD16a dual engager of the presentinvention synthesised in Biological Example 1 (Q1; SEQ ID NO: 5) was evaluated in anin vivo model using the NSG-Tg(Hu-IL15) Jackson (NOD.C8-Prkdcscid Il2rgtm1WjlTg(IL15)1Sz / SzJ) mouse.500,000 MM.1S cells containing a luciferase gene wereinoculated by i.v. infusion. 4 days after inoculation, mice were randomized into threegroups based on initial bioluminescence and Group 1 received vehicle whereas micein groups 2 and 3 received 1 million peripheral blood NK cells isolated from a healthydonor. Administration was by i.v. infusion. Daily, on day 4 to 13, animals in group 3received 6.9 mg / kg of the engager (Q1; SEQ ID NO: 5) whereas animals in group 1and 2 received vehicle. Administration was by s.c. injection. Bioluminescence signalwas measured on day 0, 4, 11, 16, 23, 27, 29 and at the end of the study on day 33. Results MM.1S cell expansion in bone and soft tissue was apparent by live animal bioluminescence measurements. Data show that i.v. administration of 1 million NKcells has an inhibitory effect on growth of the multiple myeloma cell line in the NSG-TG(Hu-IL15) model. Notably, addition of NK cells in combination with theheterotrimeric hBCMA × hCD16a dual engager (Q1; SEQ ID NO: 5) resulted in evenmore pronounced growth inhibition (Figure 7). Thus, it can be concluded that theengager of the invention (Q1; SEQ ID NO: 5) has in vivo pharmacological activity inthe multiple myeloma animal model. Preparative Example 6 Production of comparative engagers for evaluation of the invention (Comp1 & Comp2) Comparative heterotrimeric hBCMA × hCD16a dual engagers ‘Comp1’ and ‘Comp2’ (SEQ ID NOs: 7 and 8 respectively) were expressed as soluble gene products in E. coli (DE3). Cloning, expression and isolation of engagers were performed as described inPreparative Example 1. Comp1 (SEQ ID NO: 7) and Comp2 (SEQ ID NO: 8) (seesequences listed in Table 9 below) are engagers described in Example 12 of patentpublication WO2023 / 232911, where they are listed as Example compounds SEQ ID NO: 128 and 129 respectively.Table 9: Sequences of comparative compounds Comp1 and Comp2.Comparator Descriptive ID Sequence No. / SEQ ID CD16a binder NO: Comp1 H_aBCMA-1- VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLM E6_10aa_aBCMA- DDPSQSANLLAEAKKLNDAQAPKGGGSGGGGSGV SEQ ID NO: 7 1- DNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMD E6_10aa_aCD16- DPSQSANLLAEAKKLNDAQAPKGGGSGGGGSGVD NKFNKEVQMAQFEIRKLPNLNHHQSFAFIKSLMDD A10_OH PSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 1 in WO2023 / 232911) Comp2 H_aBCMA-1- VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLM E6_10aa_aBCMA- DDPSQSANLLAEAKKLNDAQAPKGGGSGGGGSGV SEQ ID NO: 8 1- DNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMD E6_10aa_aCD16- DPSQSANLLAEAKKLNDAQAPKGGGSGGGGSGVD NKFNKELQYAQKEIRRLPNLNHHQVFAFINKLIDDP A10(2a-E06)_OH SQSANLLAEAKKLNDAQAPK (SEQ ID NO: 17 in WO2023 / 232911) Biological Example 7: NK cell activation by heterotrimeric hBCMA × hCD16a dual engagers in the presence or absence of target cells The functionality of heterotrimeric hBCMA × hCD16a dual engagers of the invention Q1, Q2 (SEQ ID NOs: 5 & 6), as well as comparators Comp1 (SEQ ID NO: 7) and Comp2 (SEQ ID NO: 8) (see Preparative Example 6), were assessed in a cell-based assay using isolated NK cells from peripheral blood. PBMCs were isolated from buffy coats of healthy blood donors through density gradient isolation with Lymphoprep (Stemcell Technologies, Cambridge, UK). Untouched NK cell isolation was carried out on an autoMACS Pro separator (Miltenyi Biotec, Bergisch Gladbach, Germany). NK cells were then cultured overnight in RPMI-1640 (Sigma-Aldrich, Darmstadt, Germany) containing IL-15 (5 ng / mL) (Miltenyi Biotec, Bergisch Gladbach, Germany),before the start of in vitro assays. Engagers, at the concentration of 100nM, wereincubated with NK cells with or without multiple myeloma cell lines. For Q2 (SEQ IDNO: 6), as well as comparators Comp1 (SEQ ID NO: 7), and Comp2 (SEQ ID NO: 8)MM.1S and AMO-1 at an effector to target ratio of 1:1 for 5h was used. In a separate experiment, Q1 (SEQ ID NO:5) was evaluated using MM.1S and genetically engineered BCMA-MM.1S at an effector to target ratio of 1:1 for 6 h. The fraction of NK cells positive for the degranulation marker CD107a and the cytokine IFNg was evaluated by flow cytometry.Antibodies H4A3 and 4S.B3 were used for CD107a and interferon ^ staining,respectively (both from BD Biosciences, San Jose, USA), according to the supplier's recommendations. GolgiStop (BD Biosciences, San Jose, USA) was added after 1 hourat a concentration of 1 / 1500.Results Results are shown in Figure 8. All heterotrimeric hBCMA × hCD16a dual engagers Q1& Q2 (SEQ ID NOs: 5 & 6), Comp1 (SEQ ID NO: 7), and Comp2 (SEQ ID NO: 8), showedrobust activation of NK cells in the presence of the BCMA-expressing myeloma cell lines. Induction of interferon ^^or CD107a in the absence of target cells was negligible for Q1 and Q2 (SEQ ID NOs: 5 & 6). The low percentage of NK cells positive for interferon ^^or CD107a in the presence of Q1 and BCMA negative MM.1S further illustrate the dependence of BCMA target for activity. In contrast, comparator compounds Comp1 and Comp2 showed a greater degree of spontaneous activation in the absence of BCMA positive target cells. A reduced level of non-specific, spontaneous activation in the absence of target cells means that the risk of potentially harmful off-target effects in the clinic is reduced. Thus, Q1 and Q2 (SEQ ID NOs: 5 and 6) showed preferred properties as compared to the other evaluated engagers. Biological Example 8CD16 receptor activation by heterotrimeric hBCMA × hCD16a dual engagers in theabsence of target cells The functionality of the CD16a polypeptides of the invention synthesised inPreparative Example 1 (Q1 and Q2; SEQ ID NOs: 5 and 6), which are heterotrimerichBCMA × hCD16a dual engagers, were assessed in a cell based CD16 activationJurkat-Lucia™ Luciferase reporter assay in the absence of MM.1S multiple myelomacells to evaluate the potential for non-specific activation at high saturatingconcentrations. Comparator engagers Comp1 (SEQ ID NO: 7), and Comp2 (SEQ IDNO: 8), described in Preparative Example 6 above, were also tested in the same assay as comparators.CD16 activation Jurkat-Lucia™ Luciferase reporter assayThe propensity of the hBCMA × hCD16a dual engagers of the invention to stimulateCD16 activation in absence of MM.1S multiple myeloma cells was assessed in a Lucia Luciferase reporter assay according the method in Biological Example 2. ResultsThe results are shown in Table 10. It can be seen that the comparative hBCMA ×hCD16a dual engagers tested induced CD16 activation in the Lucia Luciferasereporter assay in the absence of BCMA expressing MM.1S cells to some degree. ForQ1 and Q2 (SEQ ID NOs: 5 & 6) non-specific activation in the absence of targets cellswas negligible whereas Comp1 and Comp2 (SEQ ID NOs: 7 & 8) showed a small butsignificant activation in the absence of target cells. Thus, Q1 and Q2 show a moreadvantageous activation profile with strict dependency on the presence of target cells.Table 10: Level of non-specific CD16a activation in absence of target cells forcompounds of the invention and comparators. CD16 receptor activation at 200nM in the absence of target cells Compound Activity (%) SD (%) Replicates (n)Q1 -0.4 3.2 4Q2 0.7 1.4 8Comp1 7 2 12Comp2 14.7 5.2 4Biological Example 9 Plasma stability of heterotrimeric hBCMA × hCD16a dual engagers of the invention The stability of CD16a-binding polypeptides of the present invention that areheterotrimeric hBCMA × hCD16a dual engagers, Q1 and Q2 (SEQ ID NOs: 5 and 6) inplasma from three different species was evaluated by liquid chromatography massspectrometry (LC-MS) analysis. The polypeptides were incubated in mouse,cynomolgus monkey and human plasma. Preparation of incubated samples prior to LC-MS analysisPlasma was spiked with Q1 or Q2 (SEQ ID NOs: 5 and 6) to a final concentration of 1mg / mL. The plasma samples were subsequently incubated at 37°C. Aliquots of 20 µL spiked plasma were removed after 0, 24, and 48 hours. PBS (20 µL) was added to the samples prior to heat treatment at 90°C for 5 minutes in an Eppendorf Thermomixerwith gentle stirring at 450 rpm (to precipitate plasma proteins, but not thepolypeptides under investigation). The samples were transferred to a precooledcentrifuge (4°C) and centrifuged for 20 minutes at 13500 x g. The supernatants (20µL) were carefully transferred to a 96-well plate and diluted with 80 µL PBS. Injection of each sample into the LC-MS System was subsequently performed. LC-MS analysis LC-MS analysis was performed using an Agilent 1290 Infinity II LC system coupled to an Agilent 6545 quadrupole-time-of-flight (Q-TOF) mass spectrometer. A Phenomenex bio-Zen intact XB-C8 column (2.1x100 mm, 3.6 µm) was used for the LC separation. The mobile phase buffer A consisted of 0.1% formic acid in ultrapure water, and buffer B consisted of 0.1% formic acid in acetonitrile (LC-MS grade). Gradient conditions were 1-90% B during 10 min. The mobile phase flow rate was 0.5 mL / min. An injection volume of 3 µL was injected into the LC-MS system. The detection was accomplished using Dual AJS electrospray ionization in positive ion mode, with the scanning range from 500 to 3000 m / z. Data collection was performed using Agilent MassHunter WorkStation software. The data analysis algorithm Maximum entropy charge deconvolution was used for the determination of molecular mass of the intact proteins. Results The results are shown in Table 11. Deconvoluted peak heights, corresponding to intact polypeptides (aa1-194), were compared within each sample after 0, 24, and 48hours incubation in plasma. Q1 was found to be more stable than Q2 in monkeyplasma, while both polypeptides showed high stability in human plasma. Q1 washighly stable in both human plasma (decrease from 97% intact protein to 96% after48 hours incubation) and in monkey plasma (no decrease observed), while in mouseplasma a decrease from 98 to 84% was observed. Q2 was highly stable in humanplasma (no decrease observed after 48 hrs incubation). In both monkey and mouseplasma, a decrease of intact Q2 was observed (from 95% to 87% in monkey plasmaand from 94% to 80% in mouse plasma). However, the magnitude of this decreasefor Q2 was much less in monkey plasma, i.e. the compound was more stable inmonkey plasma than in mouse plasma. Stability in monkey plasma is a potentially useful property in pre-clinical testing of therapeutic compounds, as primates are physiologically more similar to humans and therefore more clinically relevant as a model in some contexts. Stability in humanplasma is especially important for compounds that will be used in treatment ofhuman patients in the clinic. Dual engagers of the invention Q1 and Q2 (SEQ ID NOs:5 & 6) were both advantageously found to be highly stable in human plasma.Table 11: Plasma stability over time for dual engagers of the invention (Q1 and Q2,SEQ ID NOs.5 and 6). Q1 Mouse plasma Monkey plasma Human plasmaIncubation time % intact protein % intact protein aa1- % intact protein aa1-194 (hrs) aa1-194 194 098 98 9724 91 98 9748 84 98 96Q2 Mouse plasma Monkey plasma Human plasmaIncubation time % intact protein % intact protein aa1- % intact protein aa1-194 (hrs) aa1-194 194 094 95 9524 89 87 9548 80 87 95Preparative Example 10Preparation of 6-His-tagged heterotrimeric hBCMA × hCD16a dual engager of theinventionTable 12: Sequence of His-tagged example compound Q2 (‘Q3’).Example CD16a Sequence Compound / binder SEQ Seq ID NoID NO:Q3SEQ ID NO: 3 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPKGGGSGGGG SEQ ID NO: 9 SGVDNKFNKENQFADEEIAALPNLNFYQKWAFIR KLMDDPSQSANLLAEAKKLNDAQAPKGGGSGG (His-tagged GGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAF version of Q2) IKSLLDDPSQSANLLAEAKKLNDAQAPKYYLEHHH HHHA 6-His-tagged CD16a-binding polypeptide of the present invention that is aheterotrimeric hBCMA × hCD16a dual engager (‘Q3’), having the sequence shownabove (SEQ ID NO: 9), was expressed as a soluble gene product in E. coli (DE3).Cloning, expression and isolation of the engager was performed as described in Preparative Example 1. The Q3 engager prepared in this Example is a C-terminal 6- His-tagged version of the dual engager Q2 (SEQ ID NO: 6). Biological Example 11Selective binding of an engager of the invention: screening of a library of 6111 full-length human secreted and plasma membrane proteins The Retrogenix Cell Microarray Technology platform was used to screen for specificoff-target binding interactions of the His-tagged protein Q3 (SEQ ID NO: 9;synthesised in Example 10 above, also referred to in this report as “test article”). Investigation of the levels of binding of the test article to fixed untransfected HEK293 cells, and to cells over-expressing TNFRSF17 (BCMA), FCGR3A (CD16A) or FCGR3B (CD16B), showed 2 µg / mL of test article to be a suitable screening concentration. Therefore, in a library screen, 2 µg / mL of test article and 2 µg / mL of an isotype negative control lacking CD16a and hBCMA binding activity (or “null”) was screenedfor binding against fixed HEK293 cells, individually expressing 6111 full-length humanplasma membrane proteins, secreted and cell surface-tethered human secretedproteins plus a further 403 human heterodimers. This revealed 6 library interactionsaltogether. Each library interaction was re-expressed, along with a requested receptor (FCGR3A [CD16A] tethered secreted form) and 2 control receptors and re- tested with test article or control treatments. This was performed on both fixed and live cells. Test article Q3 (SEQ ID NO: 9) showed a significant specific interaction with primary targets TNFRSF17 (BCMA) and FCGR3B (CD16B, tethered secreted form) on both fixed and live cell microarrays, and with FCGR3B (CD16B, plasma membrane form) on the live cell microarray only. Although classed as non-specific, the SNR values for primary target FCGR3A (CD16A), expressed alone or as part of a heterodimer with FCER1G or CD247, were markedly greater than those for the negative controls, indicating specific binding over and above the negative controls. No additional interactions were observed for the test article on either fixed or livecell microarrays, indicating high specificity of test article Q3 (SEQ ID NO: 9) for its primary targets. A summary of signal to noise ratios for the different interactions is presented in Table 13.Table 13: Target-specific interactions of a C-terminal 6-His-tagged dual engager ofthe invention compared to isotype negative control. ExampleGene ID UniProtUnique Signal to noise ratios Comp / ID clone # (SNR) SEQ ID in Library Confirmation Confirmation Comment NO screen screen screen fixed screen live fixed cells cells cells Median Median Median (n=8) (n=4) (n=4) Q3TNFRSF17 Q02223- 172Q 5.84 8.29 5.19 PlasmaSEQ ID 1 membrane NO: 9FCGR3B O75015- 2117 5.92 10.82 3.03 GPI1 anchored FCGR3B O75015- 5038 4.65 3.70 5.78 Secreted -1 anchored FCGR3A6071 2.19 2.48 6.00 Heterodimer+FCER1G FCGR3A6072 4.56 4.22 3.37 Heterodimer+CD247 FCGR3A C9JC71 1968 7.37 5.11 2.15 Plasmamembrane IsotypeTNFRSF17 Q02223- 172Q -0.02 -0.03 Single passnegative 1 Membrane control protein FCGR3B O75015- 2117 0.12 -0.15 GPI1 anchored FCGR3B O75015- 5038 -0.08 -0.24 Secreted -1 anchored FCGR3A6071 2.66 -2.1 Heterodimer+FCER1G FCGR3A6072 -0.07 0.25 Heterodimer+CD247 FCGR3A C9JC71 1968 0.71 -0.73 Plasmamembrane Preparative Example 12Conjugation of a fluorescent label to a heterotrimeric hBCMA × hCD16a dualengager of the inventionAn Alexa FluorTM 647-tagged version of the hBCMA x hCD16a dual engager of thepresent invention Q1 (with SEQ ID NO: 5), termed ‘Q4’, was prepared as follows:Table 14: Sequence of Alexa FluorTM647-tagged example compound Q1 (‘Q4’). Example Label + Attach- Binder Sequence Compound ment point + Attachment pointQ4 Alexa Fluor™hBCMA, VDNKFNKENQFADEEIAALPNLNFYQKW 647 hBCMA, AFIRKLMDDPSQSANLLAEAKKLNDAQA hCD16a PKGGGSGGGGSGVDNKFNKENQFADEE IAALPNLNFYQKWAFIRKLMDDPSQSAN COOH LLAEAKKLNDAQAPKGGGSGGGGSGVD N-term NKFNKEQQIAQYEIRRLPNLNHHQTFAFI KSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5) Synthesis of example compound Q4Example compound Q4 was synthesized as follows: A solution of example compoundQ1 (SEQ ID NO: 5) (8.0 mg) in DMF (1.0 mL) was treated with a solution of AlexaFluor™ 647 NHS ester (0.4 mg) in DMF (200 µL) followed by DIPEA (1 µL). AlexaFluor™ 647 NHS ester was obtained from ThermoFisher Scientific, catalogue no.A2006. The resulting mixture was kept stirring at room temperature for 2 h, in thedark, and monitored by LCMS analysis. After 2 h, additional Alexa Fluor™ 647 NHSester (0.4 mg, dissolved in 200 µL DMF) was added followed by DIPEA (1 µL), and theresulting mixture was allowed to stir for a further 2 h. The crude material waspurified by prep-HPLC (TFA condition) and the final product was lyophilized from 0.1 % TFA in water to afford the trifluoroacetate salt (1.8 mg, 10% yield) as a blue solid.High-Res MS: calculated average mass (neutral) from measured values (m / z) showeda mixture of 0:1:2:3-labels at a ratio of 22:47:22:9 = 21194 Da, 22035 Da, 22876 Da, 23717 Da. Preparative Example 13Conjugation of biotin tag to a heterotrimeric hBCMA × hCD16a dual engager of theinventionA biotinylated version of the hBCMA x hCD16a dual engager of the present inventionQ1 (with SEQ ID NO: 5) was prepared as follows:Table 15: Sequence of biotinylated example compound Q1 (‘Q5’).Example Compound Label + Attach-Binder Sequence ment point + Attachment pointQ5 EZ-Link™hBCMA, VDNKFNKENQFADEEIAALPNLNFY Sulfo-NHS- hBCMA, QKWAFIRKLMDDPSQSANLLAEAK Biotin hCD16a KLNDAQAPKGGGSGGGGSGVDNK FNKENQFADEEIAALPNLNFYQKWA COOH N-term FIRKLMDDPSQSANLLAEAKKLNDA QAPKGGGSGGGGSGVDNKFNKEQ QIAQYEIRRLPNLNHHQTFAFIKSLLD DPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5) Synthesis of example compound Q5Example compound Q5 was synthesized as follows: the TFA salt of examplecompound Q1 (SEQ ID NO: 5) (5.0 mg) was dissolved in PBS buffer pH 7.4 (1.0 mL),and the solution pH was adjusted with 1 M NaOH until reaching pH 6. After placing the reaction vessel in an ice-bath, the previous solution was treated with a sufficient volume of 10 mM NHS-Biotin (solution in DMF) to achieve a 5-fold molar excess ofbiotin over the peptide in solution. NHS-Biotin reagent was EZ-Link™ Sulfo-NHS-Biotin, obtained from ThermoFisher Scientific, catalogue number 21217. The resulting mixture was kept stirring at room temperature for 80 min. The crude material was purified by prep-HPLC (TFA condition) and the final product was lyophilized from 0.1% TFA in water to afford the trifluoroacetate salt (1.5 mg, 13% yield) as a white solid. High-Res MS: calculated average mass (neutral) from measured values (m / z) showed a mixture of 0:1:2:3-labels at a ratio of 5.6:45.1:40.3:9 = 21194 Da, 21421 Da, 21647 Da, 21873 Da. Preparative Example 14Production of further recombinant engagers for evaluation of the presentinvention Additional CD16a-binding polypeptides of the present invention that are heterotrimeric hBCMA × hCD16a dual engagers having the sequences shown in Table16 below were expressed as soluble gene products in E. coli (DE3). Cloning,expression and isolation of engagers were performed as described in Preparative Example 1. Mass spectrometry analysis of a subset of these recombinant engagers, together with two engagers of the invention (Q1 and Q2, SEQ ID NOs: 5 & 6) and the compounds produced in Preparative Examples 10, 12 and 13 (Q3, Q4 and Q5), wasperformed using an Agilent 1290 Infinity II LC system coupled to an Agilent 6545quadrupole-time-of-flight (Q-TOF) mass spectrometer. A Phenomenex bio-Zen intact XB-C8 column (2.1x100 mm, 3.6 µm) was used for the LC separation. The data analysis algorithm Maximum entropy charge deconvolution was used for the determination of molecular mass of the intact proteins. A further set of ‘comparator’ recombinant engagers, Comp3, Comp4, Comp5 andComp6 (SEQ ID NOs. 12, 13, 14 and 15 respectively), which are described in Examples11 and 14 of patent publication WO2023 / 232911 as SEQ ID NOs. 103, 88, 94 and121, were also produced as described above.Sequences of all recombinant engagers are shown in Table 16 below and results ofthe mass spectrometry characterisation are shown in Table 17.Table 16: Details of recombinant engagers for evaluation of the present invention.Example CD16a Sequence Compound / binder SEQ ComparatorID NO:SEQ ID Q6SEQ ID NO: 2 GSSHHHHHHYYLEVDNKFNKENQFADEEIAALPNLSEQ ID NO: 10NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKENQFADEEIAALPNL NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNL NHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAP KGGGSGPSRLEEELRRRLTE Q7SEQ ID NO: 3 GSSHHHHHHYYLEVDNKFNKENQFADEEIAALPNLSEQ ID NO: 11NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKENQFADEEIAALPNL NFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNL NHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAP KGGGSGPSRLEEELRRRLTE Comp3 MMVDNKFNKENQFADEEIAALPNLNFYQKWAFIR SEQ ID NO: 12KLMDDPSQSANLLAEAKKLNDAQAPKGGGSGGG (Seq ID NO: GSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIR 103 in WO KLMDDPSQSANLLAEAKKLNDAQAPKGGGSGGG GSGVDNKFNKEVQMAQFEIRKLPNLNHHQSFAFIK 2023 / 232911) SLMDDPSQSANLLAEAKKLNDAQAPKYYHHHHHH Comp4 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLM SEQ ID NO: 13DDPSQSANLLAEAKKLNDAQAPKGGGSGGGGSG (SEQ ID NO: 88 GGGSGVDNKFNKEVQMAQFEIRKLPNLNHHQSFA in WO FIKSLMDDPSQSANLLAEAKKLNDAQAPKYYHHHH HH 2023 / 232911) Comp5 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLM SEQ ID NO: 14DDPSQSANLLAEAKKLNDAQAPKGGGSGGGGSG (SEQ ID NO: 94 GGGSGVDNKFNKELQYAQKEIRRLPNLNHHQVFA in WO FINKLIDDPSQSANLLAEAKKLNDAQAPKYYHHHH HH 2023 / 232911) Comp6 VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLM SEQ ID NO: 15DDPSQSANLLAEAKKLNDAQAPKGGGSGGGGSG (SEQ ID NO: GGGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAF 121 in WO IKSLLDDPSQSANLLAEAKKLNDAQAPKYYHHHHH H 2023 / 232911)Table 17: Mass spectrometry characterization of dual engagers of the invention,engagers described in Preparative Examples 10, 12 and 13, and further recombinant engagers for evaluation of the invention. ExampleChemical Formula CalculatedCalculated average Compound Molecular mass (neutral) No. / SEQ weight ID Q2 (SEQ IDC935H1458N264O294S2 21165.6 21166.0NO: 6) Q1 (SEQ IDC935H1458N266O294S2 21193.6 21194.0NO: 5) Q6 (SEQ IDC1093H1694N322O343S2 24897.6 24898.1NO: 10) Q3 (SEQ IDC1000H1536N286O308S2 22557.1 22557.6NO: 9) Q7 (SEQ IDC1093H1694N320O343S2 24869.6 24870.1NO: 11) Q5 C945H1472N268O296S3 21420.0 21420.9Q4 C971H1502N268O307S6 22034.6 22035.0Biological Example 15 Tagged and labelled versions of the engagers of the invention retain biological activity The impact of introducing additional tag-sequences into engagers of the inventionwas assessed in a cell-based CD16 activation Jurkat-Lucia™ Luciferase reporter assayin the presence or absence of MM.1S multiple myeloma cells.CD16 activation Jurkat-Lucia™ Luciferase reporter assayThe propensity of the hBCMA × hCD16a dual engager to stimulate CD16 activation was assessed in a Lucia Luciferase reporter assay and compared to the antibody dependent cellular cytotoxicity (ADCC) potency of Elotuzumab (clinical grade a-SLAMF7 monoclonal antibody) through evaluation of CD16a activation according tothe method in Biological Example 2. Results The results are shown in Table 18. It can be seen that the tagged and labelled hBCMA × hCD16a dual engagers of the present invention induced CD16 activation in the Lucia Luciferase reporter assay in the presence of BCMA expressing MM.1S cells. It can be seen that the mean EC50remains low in the tagged variants and biologicalactivity is retained. Thus, it can be concluded that a His-tag at the N-terminus or C-terminus of the polypetides does not interfere with biological function. The same applies for a biotin tag, a fluorescent tag, a C-terminal alfa tag and adding two additional methionines at the N-terminus. Therefore, it can be concluded that adding a variety of tag moieties to compounds of the invention does not impair their biological activity.Table 18: CD16a activation of tagged / labelled hBCMA × hCD16a heterotrimeric dualengagers of the invention, when tested at 10 concentrations ExampleMean EC50 (nM) Tag - Modification Assay SetupCompound / SEQ ID No Q60.44 N-terminal His tag andA SEQ ID NO: 10 C-terminal Alfa tag on Example Compound Q1 (SEQ ID NO: 5) Q5 0.06 Biotin on ExampleB Compound Q1 (SEQ ID NO: 5) Q4 1.34 Alexa647 on ExampleB Compound Q1 (SEQ ID NO: 5) Q3 SEQ ID0.10 C-terminal His tag onB NO: 9 Example compound Q2 SEQ ID NO: 6 Q7 SEQ ID 92% at 200 nM N-terminal His tag and A, conducted with 2 NO: 11 75% at 20 nM C-terminal Alfa tag on concentrations Example compound instead of full dose Q2 SEQ ID NO: 6 response

[0004] Preparative Example 16 Production of synthetic heterodimeric CD16a binding polypeptides for evaluation of the present invention Synthesis, purification and analysis of monomeric hBCMA and hCD16a binding polypeptides General method for synthesis of monomeric hBCMA and hCD16a binding polypeptides The monomeric hBCMA and hCD16a binding polypeptides were constructed by means of linear solid-phase peptide synthesis (SPPS), starting from the C-terminus amino acid. The method of synthesis employed Fmoc solid-phase peptide synthesis, on a Symphony X peptide synthesizer from Gyros Protein Technologies. A pre-loadedWang resin was used to obtain an acid substrate. Standard Fmoc-amino acids wereemployed with appropriate side chain protecting groups, including the modified Fmoc-amino acid building blocks and the following special building blocks containing alkyne or azide functionalities: Standard coupling conditions were used to synthesise each polypeptide. In some instances, pseudoproline di-peptides were used. In some instances, some amino acids were double coupled. Reactions were carried out in DMF at room temperature.The general synthetic workflow on the polymeric support can be summarized in thefollowing steps: 1. Swelling of the resin with DMF; 2. Cleavage of the temporary protecting Fmoc group; 3. Washing of the resin with DMF; 4. Coupling of the second Fmoc-amino acid to a pre-loaded Wang resin; 5. Capping of any unreacted amino group; 6. Cleavage of the temporary protecting Fmoc group; 7. Coupling of a further Fmoc-amino acid or Fmoc-dipeptide; 8. Repeating steps 5 to 7 to form the desired polypeptide sequence; 9. Coupling of the last Fmoc-amino acid of the polypeptide; 10. Cleavage of the temporary protecting Fmoc group; 11. Cleavage of the polypeptide from the resin and simultaneous removal of the side chain protecting groups. After cleavage from the resin, the polypeptides were purified by reverse phase HPLC using acetonitrile / water / TFA. The fractions were analysed by LCMS, and the appropriated fractions were pooled and lyophilized. General methods for purification and analysis Analytical HPLC was carried out on an Agilent Series 1260 system using a Kinetex XB C18 (2.6 µm, 3.0x100mm) column with 0.1% TFA in MiliQ H2O / CH3CN as mobile phase (acid conditions) (flow 0.85 mL / min), Electrospray ionization mass spectrometry (ESI-MS) was performed using an Agilent 6125 Series Liquid Chromatograph / Mass Selective Detector (MSD) to obtain the pseudo molecular [M+H]+ ion of the target molecules. Analytical size exclusion chromatography (SEC) was carried out on an Agilent Series 1100 system using a cytiva Superdex 75 Increase 10 / 300 GL column with 1X PBS pH 7.4 (Phosphate Buffered Saline) as mobile phase with a flow of 0.3mL / min and UV-detection at 220nm using an Agilent Series 1100 diode array detector. As acomparison, the following protein Mw markers were used: Conalbumin (75 kDa), Ovalbumin (44 kDa), Carbonic anhydrase (29 kDa), Ribonuclease A (13.7 kDa), and Aprotinin (6.5 kDa). Results Monomeric CD16a binding polypeptides having the sequences shown in Table 19 were synthesised and purified. Table 19: Synthetic monomeric CD16a-binding polypeptide sequences.SyntheticSequence / SEQ ID NO. CommentCompound Name / SEQ ID C1 (N3)KGSGGSGGVDNKFNKE SEQ ID NO: VQMAQFEIRKLPNLNHHQSF 16 AFIKSLMDDPSQSANLLAEAK KLNDAQAPK (SEQ ID NO: 16) “(N3)K” is C6 (N3)KVDNKFNKELQYAQKEI SEQ ID NO: RRLPNLNHHQVFAFINKLIDD 17 PSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 17) “(N3)K” is C10 (Pryoc)KVDNKFNKEQQIAQY SEQ ID NO: EIRKLPNLNHHQTFAFIKSLLD 18 DPSQSANLLAEAKKLNDAQA PK (SEQ ID NO: 18) “(Pryoc)K” is C17 6-azidohexanamide- SEQ ID NO: VDNKFNKEQQIAQYEIRRLPN ““6-azidohexanamide“ is 19 LNHHQTFAFIKSLLDDPSQSA NLLAEAKKLNDAQAPK (SEQ ID NO: 19) Monomeric hBCMA-binding polypeptides having the sequences shown in Table 20 were synthesised and purified. Table 20: Synthetic monomeric hBCMA-binding polypeptide sequences.Name / Sequence CommentSEQ ID B1 VDNKFNKENQFADEEIAALPNLNFYQ SEQ ID NO: 20 KWAFIRKLMDDPSQSANLLAEAKKLN DAQAPKGGSGGSGK(Pryoc) (SEQ ID NO: 20) “K(Pryoc)” is B3 VDNKFNKENQFADEEIAALPNLNFYQ SEQ ID NO: 21 KWAFIRKLMDDPSQSANLLAEAKKLN DAQ APKGGSGGSGK(N3) (SEQ ID NO: 21) “K(N3)” is B18 6-azidohexanamide- SEQ ID NO: 22 VDNKFNKENQFADEEIAALPNLNFYQ“6-azidohexanamide” is ;KWAFIRKLMDDPSQSANLLAEAKKLN DAQAPKGGSGGSGK(Pryoc) (SEQ ID NO: 22) “K(Pryoc)” is Assembly of functional synthetically produced hCD16a × hBCMA dual engager dimeric constructs hCD16a × hBCMA dual engager dimeric constructs were synthesised by reacting thepolypeptides of Tables 19 and 20 above in a copper-catalysed azide-alkyne clickchemistry reaction according to General Method A or B below. General method A for the synthesis of hBCMA × hCD16a dual engager dimeric constructs A mixture of compounds (alkyne)peptide (1.0 eq), (azide)peptide (1.0 eq), and BTTAA (1.5 eq) were dissolved in PBS buffer pH 7.4 (purged with N2), and then CuSO4 (1.5 eq) and sodium ascorbate (3.0 eq) were added, and the vessel was purged with N2.The reaction mixture was stirred at room temperature and monitored by LCMS analysis. The crude mixture was purified by reversed-phase HPLC chromatography using acetonitrile / water / TFA gradient on a C18 column, and fractions containing the final polypeptide product were pooled and lyophilized. General method B for the synthesis of hBCMA × hCD16a dual engager dimeric constructs A mixture of compounds (alkyne)peptide (1.2 eq), (azide)peptide (1.0 eq), and BTTAA (1.5 eq) were dissolved in PBS buffer pH 7.4 (purged with N2), and then CuSO4(1.5 eq) and sodium ascorbate (3.0 eq) were added, and the vessel was purged with N2.The reaction mixture was stirred at room temperature and monitored by LCMS analysis. The crude mixture was purified by reversed-phase HPLC chromatography using acetonitrile / water / TFA gradient on a C18 column, and fractions containing the final polypeptide product were pooled and lyophilized. Results hCD16a × hBCMA dual engager dimeric constructs having the structures shown in Table 21 below and Figure 9 were synthesised. The yield and purity of each syntheticdimeric dual engager construct is shown in Table 22 below.Table 21: aBCMA:aCD16a dimeric peptides (1:1).Compound Synthetic hBCMA hBCMA poly- hCD16a hCD16a poly- Structure / Name Method poly- peptide poly- peptide sequence peptide attachment peptide attachment starting point starting point material materialL1 A B1 C-terminus C1 N-terminus See Figure 9L8 A B1 C-terminus C6 N-terminus See Figure 9L15 A B3 C-terminus C10 N-terminus See Figure 9L17 B B1 C-terminus C17 N-terminus See Figure 9Table 22: Yield and purity of dual engager dimeric constructs.Name Yield (%) Purity HPLC (%) Purity SEC (%)L1 86 97 99L8 63 99 97L15 10 95 97L17 37 99 98Mass spectrometry of the hBCMA and hCD16a monomeric synthetic constructs andthe hBCMA × hCD16a dual engager dimeric synthetic constructs High-resolution quadrupole-time-of-flight mass spectrometry was used to characterise the hBCMA and hCD16a monomeric synthetic constructs and the hBCMA × hCD16a dual engager multimeric synthetic constructs synthesised in this example (Example 16). The conditions employed were: Mobile Phases: A: 0.1% formic acid in MilliQ water. B: Acetonitrile Flow: 0.5 mL / min Column: C8, 3.6 µm, 2.1 x 100 mm (Phenomenex bioZen intact XB-C8) LC instrument: Agilent 1290 Infinity II system MS instrument: Agilent QTOF 6545 operating in positive Dual AJS ESI mode LC gradient: 0 min: 10%B; 10 min: 60%B; 10.1-12 min: 95%B; 12.1 min: 10%B Results The mass spectrometry results for the hBCMA and hCD16a monomeric syntheticconstructs are shown in Table 23; the mass spectrometry results for the hBCMA ×hCD16a dual engager dimeric synthetic constructs are shown in Table 24.Table 23: Mass spectrometry characterization of the hBCMA and hCD16a monomericsynthetic constructs. Name / Chemical Formula CalculatedCalculated average SEQ ID Molecular weight mass (neutral) B1C324H501N89O103S 7323.1 7322.8SEQ ID NO: 20 C1C314H500N94O98S2 7224.1 7223.8SEQ ID NO: 16 B3C320H497N91O101S 7267.1 7266.7SEQ ID NO: 21 C6C304H487N91O89 6840.8 6841.3SEQ ID NO:17 C10C305H484N86O93 6843.7 6844.1SEQ ID NO:18 C17C301H479N89O91 6800.7 6801.0SEQ ID NO: 19Table 24: Mass spectrometry characterization of the hBCMA × hCD16a dual engagerdimeric synthetic constructs. Name Chemical Formula CalculatedCalculated average Molecular weight mass (neutral) L1 C638H1001N183O201S3 14547.3 14547.3L8 C628H988N180O192S 14163.9 14163.9L15 C625H981N177O194S 14110.8 14110.8L17 C625H980N178O194S 14123.8 14123.8 Biological Example 17 Comparison of biological activity of heterotrimeric engagers with corresponding heterodimeric dual engagers Heterodimeric and heterotrimeric engagers were evaluated in the cell based CD16activation Jurkat-Lucia™ Luciferase reporter assay in the presence or absence ofMM.1S multiple myeloma cells as described in Biological Examples 2 and 15.Engagers were selected to illustrate the impact of dimeric and trimeric format on activity; for each heterotrimeric engager, the corresponding dimeric engager(s) hadthe same CD16a-binding moiety. All heterotrimeric and heterodimeric engagerstested (‘trimers’ and ‘dimers’) contained hBCMA-binding moieties with the samesequence (SEQ ID NO: 4). Heterotrimeric engagers of the current invention were also compared to comparator engagers described in patent publication WO2023 / 232911.Table 25 below shows all heterotrimeric engagers and corresponding dimers testedin this Example. Responses were normalized to the maximal response of Elotuzumaband efficacy (expressed as maximal activity of engagers) was compared. The resultsare shown in Figure 10.Table 25: Heterotrimeric engagers and corresponding dimeric engagers.Trimeric dual Corresponding Corresponding dimer description / ID engager / Sourcedimer(s) Q1 (SEQ ID NO: 5)L17 Synthetic dimer described in Example 16– presentinvention Q2 (SEQ ID NO: 6) Comp6 (SEQ ID Recombinant dimer described in –presentNO: 15) Example 14 invention comparator L15 Synthetic dimer described in Example 16Comp1 (SEQ ID Comp4 (SEQ ID Recombinant dimer described in NO: 7) – NO: 13) – Example 14 comparator comparator L1) Synthetic dimer described in Example 16Comp2 (SEQ ID Comp5 (SEQ ID Recombinant dimer described in NO: 8) – NO: 14) – Example 14 comparator comparator L8 Synthetic dimer described in Example 16 ResultsAs seen in Figure 10, efficacy was increased overall when comparing heterotrimericengagers containing the CD16a-binding functional portion with their corresponding heterodimeric variants (synthetic and recombinant), as illustrated by the gain inefficacy as expressed as a ratio of maximum response of the heterotrimeric engagersto maximum response of the corresponding heterodimeric engagers. Moreover, the magnitude of this gain in efficacy was surprisingly much higher for the heterotrimeric engagers of the present invention Q1 and Q2 (i.e. containing the CD16a-bindingfunctional portion SEQ ID: 2 or 3, respectively) than for the comparator compounds.

Claims

Claims 1. A CD16a-binding polypeptide which comprises at least one motif that binds to CD16a, and wherein said CD16a-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a-binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]; wherein the CD16a-binding motif sequence is: QQIAQYEIRRLPNLNHHQTFAFIKSLL (SEQ ID NO: 1).

2. A CD16a-binding polypeptide which comprises at least one motif that binds toCD16a, and wherein said CD16a-binding polypeptide comprises the following structure: [N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the CD16a-binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2]; wherein the sequence of the CD16a-binding polypeptide is: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2).

3. A CD16a-binding polypeptide as claimed in claim 1 or 2, which further comprises one or two (preferably two) additional functional portions.

4. A CD16a-binding polypeptide as claimed in claim 3, wherein each additional functional portion is a BCMA-binding polypeptide.

5. A CD16a-binding polypeptide as claimed in claim 4, wherein each additional functional portion is a BCMA-binding polypeptide which comprises at least one motif that binds to hBCMA, wherein said hBCMA binding polypeptide comprises the following structure:[N-terminal portion]-[Helix 1]-[Separating portion]-[Helix 2]-[C-terminal portion] the hBCMA binding motif being the portion [Helix 1]-[Separating portion]-[Helix 2].

6. A CD16a-binding polypeptide as claimed in claim 4 or 5, wherein each BCMA-binding polypeptide is: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4).

7. A CD16a-binding polypeptide which comprises the following structure:[BCMA-binding polypeptide]-[Linker 1]-[BCMA-binding polypeptide]-[Linker 2]-[CD16a-binding polypeptide] wherein: each of the BCMA-binding polypeptides comprises the sequence: VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide comprises the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or comprises the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 has the sequence (GGGSG)n, where n is 1, 2 or 3.

8. A CD16a-binding polypeptide as claimed in claim 7 wherein the CD16a-binding polypeptide comprises the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2)9. A CD16a-binding polypeptide as claimed in claim 7 wherein:each of the BCMA-binding polypeptides consists of the sequence:VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAP K (SEQ ID NO: 4); the CD16a-binding polypeptide consists of the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2) or consists of the sequence: VDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 3); and wherein each of Linker 1 and Linker 2 consists of the sequence (GGGSG)n, where n is 1, 2 or 3.

10. A CD16a-binding polypeptide as claimed in claim 7 or claim 9 wherein theCD16a-binding polypeptide consists of the sequence: VDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 2)11. A CD16a-binding polypeptide as claimed in any one of claims 7 to 10, whereinn is 2.

12. A CD16a-binding polypeptide as claimed in claim 7, wherein the CD16a-binding polypeptide comprises the sequence VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPKGGGS GGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 6).

13. A CD16a-binding polypeptide as claimed in claim 7, wherein the CD16a-binding polypeptide has the sequenceVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPKGGGS GGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRKLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 6)14. A CD16a-binding polypeptide as claimed in claim 8, wherein the CD16a-binding polypeptide comprises the sequence VDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPKGGGS GGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5).

15. A CD16a-binding polypeptide as claimed in claim 8, wherein the CD16a-binding polypeptide has the sequenceVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQAPKGGGS GGGGSGVDNKFNKENQFADEEIAALPNLNFYQKWAFIRKLMDDPSQSANLLAEAKKLNDAQA PKGGGSGGGGSGVDNKFNKEQQIAQYEIRRLPNLNHHQTFAFIKSLLDDPSQSANLLAEAKKLNDAQAPK (SEQ ID NO: 5).

16. A CD16a binder-drug conjugate comprising the CD16a-binding polypeptide asclaimed in any of claims 1 to 15, and an additional therapeutic agent.

17. The CD16a binder-drug conjugate as claimed in claim 16, wherein theadditional therapeutic agent is a cytotoxic drug, for example MMAF, MMAE, doxorubicin, pyrrolobenzodiazepine, amanitin, maytansinoids, duostatins, mitomycin C, desmethyltopotecan or SN-38.

18. The CD16a binder-drug conjugate as claimed in claim 16 or claim 17, whereinthe CD16a-binding polypeptide is connected to the additional therapeutic agent via a linker.

19. A pharmaceutical composition comprising a CD16a-binding polypeptide as claimed in any of claims 1 to 15.

20. A CD16a-binding polypeptide as claimed in any of claims 1 to 15, the CD16abinder-drug conjugate as claimed in any of claims 16 to 18, and / or a pharmaceuticalcomposition as claimed in claim 19, for use in medicine.

21. A CD16a-binding polypeptide as claimed in any of claims 1 to 15, the CD16abinder-drug conjugate as claimed in any of claims 16 to 18, and / or a pharmaceuticalcomposition as claimed in claim 19, for use in the treatment of cancer.

22. A CD16a-binding polypeptide as claimed in any of claims 1 to 15, the CD16a binder-drug conjugate as claimed in any of claims 16 to 18, and / or a pharmaceutical composition as claimed in claim 19, for use as claimed in claim 21, wherein the cancer is multiple myeloma.

23. Use of a CD16a-binding and BCMA-binding polypeptide as claimed in any ofclaims 1 to 15, the CD16a binder-drug conjugate as claimed in any of claims 16 to 18, and / or a pharmaceutical composition as claimed in claim 19, for the manufacture of a medicament for the treatment of cancer.

24. A method of treating cancer, the method comprising administering to apatient in need thereof a CD16a-binding and BCMA-binding polypeptide as claimed in any of claims 1 to 15, the CD16a binder-drug conjugate as claimed in any of claims 16 to 18, and / or a pharmaceutical composition as claimed in claim 19.

25. A kit comprising a CD16a-binding polypeptide as claimed in any of claims 1 to 11, the CD16a binder-drug conjugate as claimed in any of claims 16 to 18, or apharmaceutical composition as claimed in claim 19 and, optionally, one or morefurther therapeutic agent(s).

26. The kit as claimed in claim 25, wherein the one or more further therapeuticagent(s) is selected from a proteasome inhibitor (for example carlfizomib or bortezomib), an immunomodulatory agent (for example lenalidomide or thalidomide), an alkylator (for example melphalan or melflufen), a steroid (forexample dexamethasone or prednisone), an anti-CD38 agent (for example daratumumab), an immune checkpoint inhibitor (for example a CTLA-4 inhibitor, a PD-1 inhibitor, or a PD-L1 inhibitor), and an ADAM17 inhibitor.

27. The kit as claimed in claim 25 or claim 26, for use in medicine, for example inthe treatment of cancer, and especially in the treatment of multiple myeloma.

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