Compositions and methods

Abstract

The present application relates to an isolated conjugate comprising a cell or vesicle modified with a first click component, further comprising a second click component, a pharmaceutical composition and a kit comprising said modified isolated conjugate and a second click component. The present application further relates to a method for detecting the presence and / or location of a cell or vesicle in a subject, a method for directing a cell or vesicle to a target site in a subject. The present invention also relates to the use of a modified isolated conjugate further comprising a second click component or a pharmaceutical composition comprising said modified isolated conjugate and a second click component in medicine, such as treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell to a subject.

Description

[0001] Compositions and Methods The present application relates to an isolated conjugate comprising a cell or vesicle modified with a first click component, a pharmaceutical composition and a kit comprising said isolated conjugate, a method for detecting the presence and / or location of a cell or vesicle in a subject, a method for directing a cell or vesicle to a target site in a subject, the use of an isolated conjugate or a pharmaceutical composition comprising said isolated conjugate in medicine, such as treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell to a subject. The present invention finds utility, for example, in the tracking and homing of cells or vesicles in the body of a subject. Cell-based therapies have the potential to exceed the efficacy and safety profiles of traditional drugs. The mobility and versatility of cells allows them to dynamically respond to signals from the microenvironment, offering a unique opportunity for the development of effective, long-term treatment strategies. Remarkable results have been obtained in the clinical setting with immune and stem cell therapies in blood malignancies (Weber, E. W. et al., Cell 2020, 181 (1), 46-62 and Hoang, D. M. et al., Signal Transduction and Targeted Therapy 2022, 7 (1), 272). However, the biggest challenge of cell-based therapies in general, is that the fate of the cells after injection is completely unknown. This becomes especially relevant in treatment strategies for diseases in solid organs. If cells do not reach or stay at the target site, patients may be persistently treated with ineffective therapy with a risk of side effects. By the time it is realised that the treatment is unsuccessful, it may be too late to consider alternative treatment options. New methodologies to track therapeutic cells in the body are desperately needed to determine if the cells effectively reach and / or are maintained at the target site. Furthermore, to significantly improve the clinical outcome, innovative, novel strategies need to be designed to increase the specificity and efficacy of cell-based therapies. Described herein is the use of bioorthogonal click chemistry in new strategies for localising and directing cells or vesicles with unparalleled specificity after their administration to a subject. Bioorthogonal click reactions occur between two synthetic molecules with incredible specificity towards each other and – due to their unique high-speed reaction kinetics – such reactions can be performed within a living organism. Recent developments have accelerated their exploration for molecular imaging and nuclear medicine, highly increasing specificity and reducing off-target doses (Oliveira, B. L. et al., Chem. Soc. Rev. 2017, 46 (16), 4895-4950). In known methods, a dienophile (DP) such as trans-cyclooctene (TCO) or bicyclo[6.1.0]nonyne (BCN) is conjugated to an antibody which serves as the artificial in vivo binding site for a fast-clearing diene, for example a tetrazine (Tz). The reaction between DP and diene is selective, modular and – more importantly – extremely fast, with rate constants that can exceed 105-106M−1s−1.6, (Handula, M. et al, Molecules. 2021 Jul 30;26(15):4640). Against this background, the inventors have surprisingly discovered that DP-diene click chemistry can be used in: 1) a novel strategy for the tracking of cells in a subject with high specificity, and 2) an innovative method of directing cells to a target improve the efficacy of cell-based therapies. In traditional cell tracking methods, therapeutic cells are directly labelled with imaging agents (e.g. radioisotopes, fluorescent dyes) to allow the long-term visualisation of their distribution throughout the body after injection. Cells have previously been labelled with radioactive isotopes for long-term cell tracking by positron emission tomography (PET) (Friberger, I. et al., Mol. Imaging Biol. 2021, 23 (6), 952-962 and Perrin, J. et al., Frontiers in Medicine 2020). The inventors previously demonstrated that cells could indeed be traced for at least up to two weeks. However, a disadvantage with such conventional cell tracking methodologies is that injected cells produce long-lived radioactive metabolites that cause signal interference and radiotoxicity to healthy tissues. That is, the inventors demonstrated that 29-38% of radioactivity localised to off-target organs such as liver, spleen and lungs, agreeing with clinical observations using similar cell tracking methods (Friberger, I. et al., 2020 and Lapi, S et al., J. Nucl. Med. 2022, 63 (supplement 2), 2447). So far no one has been able to prove whether such off-target signals originate from actual cells that reside at the off-target tissues or, instead, from radioactive metabolites. Against this background, an innovative cell tracking strategy with improved specificity and a minimal risk of off-target radiotoxicity, based on bioorthogonal click chemistry, is provided herein (Figure 1). Immune cell therapies are showing great promise in the clinical setting, in particular in the scope of haematological malignancies where remissions of 40-89% have been reported Martino, M et al., Int. J. Mol. Sci. [Online], 2021 and Irvine, D. J. et al., Science 2022, 378 (6622), 853-858). Despite these promising results, long-term disease-free survival is often only achieved in a minority of patients. Furthermore, in the scope of solid tumours, responses to immune cell therapies are generally poor. Inventive engineering strategies have been explored to improve their efficacy, but results have so far been limited due to the development of therapy resistance, off-target binding, insufficient tumour infiltration, short-term persistence and immune cell-associated toxicity (Sterner, R et al., Blood Cancer J. 2021, 11 (4), 69). To overcome these challenges and to substantially improve the efficacy of immune cell therapies in general, novel cell homing strategies are desperately needed. Against this background a novel strategy for directing cells using click chemistry is provided herein (Fig. 2). In a first aspect, the invention provides an isolated conjugate comprising a cell or vesicle and a first click component, wherein the first click component is covalently conjugated to the cell or vesicle surface, wherein the first click component is selected from a dienophile (DP) or a diene, and wherein the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4-triazine, optionally wherein the covalent conjugation is carried out ex vivo. By “isolated” as used herein, we include the meaning of material that is removed from its original environment (e.g., the cell is removed from the organ from which the cell normally resides, or originates). Accordingly, it will be appreciated that by “isolated” we include the meaning that the material is not located or otherwise provided within its original environment. In the context of the present invention, the isolated conjugate is present outside of the human or animal body, in other words the cell or vesicle and a first click component are present as a conjugate ex vivo. It will be appreciated that the isolated conjugate comprising a cell or vesicle and a first click component is engineered and is non- naturally occurring. By “conjugate” we include the meaning of two molecular entities that are associated with one another by a direct covalent bond (i.e. the two molecular entities are covalently bound to each other, for example by a C-N or C-O bond). By “vesicle” we include the meaning of a structure comprising a liquid or cytoplasm enclosed by at least one lipid bilayer. We include vesicles that form naturally during the processes of secretion, for example, exosomes, and other extracellular vesicles derived from the membrane of cells, such as a matrix-bound nanovesicle (MBV) (Piening & Wachs, Cells Tissues Organs 2023, 212 (1), 111-123). We also include vesicles prepared artificially, for example, liposomes. Cells or vesicles can be provided (or isolated) from a subject, such as a patient or an animal, using any methods known in the art, for example, a laboratory procedure in which cells are separated from a sample of blood (such as apheresis), obtained from tissue biopsies or from biological swabs. It will be appreciated that the method chosen for providing cells or vesicles will depend on the type of cell or vesicle needed for a particular purpose. By "first click component" or “first click chemistry component” or “first component” we include the meaning of a fragment or portion of a first click component reagent that is attached to the surface of a cell or vesicle following the conjugation reaction between the first click component reagent and a biomolecule present on the surface of the cell or vesicle. For example, when the first click component reagent is TCO-NHS ester, the first click component is only the TCO fragment, i.e. the fragment of the TCO-NHS ester that is attached to the surface of the cell or vesicle. The first click component comprises a moiety that is reactive in IEDDA reaction and typically a linker moiety. By “first click component reagent” or “first click chemistry component reagent” or “first click reagent” or “first reagent” we include the meaning of a reactant that can partake in (i) a click chemistry reaction and (ii) a conjugation reaction to the surface of the cell or vesicle (i.e. the first click component reagent is used to install the first click component on the surface of the cell or vesicle). The first click component reagent comprises the first click component and a moiety that can be reacted to the cells or vesicles (a so-called cell- or vesicle-reactive moiety), such as an NHS ester or maleimide, and / or (e.g. or) a moiety that is a leaving group (i.e. that can be used to react the first click component to the cell or vesicle by eliminating the leaving group). For example, when the first click component reagent is an NHS ester, the first click component and the first click component reagent may be depicted as follows. In this example, the NHS ester group is the cell-reactive moiety. The skilled person will understand that this is a non-limiting example. The skilled person will be able to determine whether the term “first click component" or “first click component reagent” and the like as used herein refers to a reagent or to the fragment of the reagent that has been added to the surface of the cell or vesicle. The “second click component”, “second click component reagent”, “second component” and the like may be used interchangeably. These terms refer to an IEEDA reagent with complementary reactivity with respect to the first click component and / or reagent, i.e. are able to undergo a IEEDA reaction with the first click component and / or reagent. In certain embodiments, the second click component includes a detectable moiety. Exemplary click chemistry components and reagents are described in Stéen, E.J.L. et al., Biomaterials 2018, 179, 209-245 (in particular Figure 21 therein) which is incorporated by reference herein. For example, a strained alkyne, e.g., a cyclooctyne, is a click chemistry component, since it can partake in a strain-promoted cycloaddition. For two molecules to be conjugated via click chemistry, the click chemistry components have to be reactive with each other, for example, in that the reactive moiety of the first click chemistry component can react with the reactive moiety of the second click component to form a covalent bond. Such click chemistry component pairs that are reactive with each other are referred to herein as first click components and second click components (or first click component reagents and second click component reagents, respectively). For example, if a cyclooctene is a first click chemistry component, a 1,2,4,5- tetrazine is a second click component. The present invention includes the use of click chemistry pairs, such as Diels-Alder pairs, that include a diene and a dienophile. In an embodiment, the first and second click components are any click chemistry components that can participate in an inverse electron demand Diels-Alder cycloaddition (IEDDA) reaction. The inverse electron demand Diels- Alder cycloaddition (IEDDA) reaction of a diene (e.g., a substituted tetrazine) with a dienophile (e.g., an alkene or alkyne), produces an unstable cycloadduct which subsequently undergoes a retro-Diels-Alder cycloaddition reaction to produce dinitrogen as a byproduct and the desired dihydropyrazine (after reaction with an alkene) or pyrazine (after reaction with an alkyne) products (See Blackman et al., J. Am. Chem. Soc. 2008; 130, 13518-13519). The dihydropyrazine product may undergo an additional oxidation step to generate the corresponding pyrazine. For example, strained alkene dienophiles such as trans-cyclooctene (TCO), norbornene, or biscyclononene can be paired with a suitable tetrazine (Tz) dienophile as a click chemistry pair (See Blackman et al., J. Am. Chem. Soc. 2008; 130, 13518-13519). Such dienes and dienophiles are well known to those of skill in the art and include, but are not limited to, those described in Oliveira B. L. et al, Chem. Soc. Rev., 2017, 46, 4895- 4950 and Spicer C. et al, Nature Communications. 2014; 5:4740; the former discusses the rates of reaction between many different tetrazines and TCOs, providing a guide to selecting the most appropriate reactive pairs of click chemistry components. Unless otherwise specified, alkyl groups defined herein may be straight-chain or, when there is a sufficient number (e.g. a minimum of three) of carbon atoms, be branched-chain and / or cyclic. Alkyl groups that may be mentioned include methyl, ethyl, propyl, iso- propyl, butyl, and tert-butyl. As used herein, “alkylene” (i.e. alkanediyl) refers to a divalent alkyl group. Particular alkylene groups that may be mentioned include, for example, methylene (i.e. -CH2-). Alkenyl groups are unsaturated alkyl groups (i.e. having at least one carbon–carbon double bond). Unless otherwise specified, alkenyl groups defined herein may be straight-chain or, when there is a sufficient number (i.e. a minimum of two or three, as appropriate) of carbon atoms, be branched-chain and / or cyclic. Alkenyl groups that may be used include ethenyl, propenyl, and butenyl groups. When used herein, “alkenylene” (i.e. alkenediyl) refers to a divalent alkenyl group. Particular alkenylene groups that may be mentioned include, for example, -CH=CH-. Alkynyl groups are unsaturated alkyl groups (i.e. having at least one carbon–carbon triple bond). Unless otherwise specified, alkynyl groups defined herein may be straight-chain or, when there is a sufficient number (i.e. a minimum of two or three, as appropriate) of carbon atoms, be branched-chain and / or cyclic. Alkynyl groups that may be used include ethenyl, propenyl, and butenyl groups. When used herein, “alkynylene” (i.e. alkynediyl) refers to a divalent alkenyl group. Particular alkynylene groups that may be mentioned include, for example, -C≡C-. Heterocycloalkyl groups that may be mentioned include non-aromatic monocyclic heterocycloalkyl groups in which at least one (e.g. one to four) of the atoms in the ring system is other than carbon (i.e. a heteroatom, e.g. sulphur, oxygen or, particularly, nitrogen), and in which the total number of atoms in the ring system is from four to six. Heterocycloalkyl groups include unsaturated groups (e.g. comprising carbon-nitrogen or carbon-carbon double bonds). The point(s) of attachment of heterocycloalkyl groups may be via any atom in the ring system including (where appropriate) a heteroatom (such as a nitrogen atom), or an atom on any fused carbocyclic ring that may be present as part of the ring system. Heterocycloalkyl groups may also be in the N- or S- oxidised form (i.e. those heteroatoms may be substituted with one or two =O substituents, as appropriate). For the avoidance of doubt, optional substituents include those defined herein. Heterocycloalkyl groups that may be mentioned include, but not limited to, pyrrolidinonyl, pyrrolidinyl, pyrrolinyl, pyranyl, pyrazolidinyl, tetrahydropyranyl, piperazinyl, piperidinyl, thiolanyl, sulfolanyl, thianyl and the like. Aromatic (i.e. aryl) groups that may be mentioned include C6-14 aryl groups (e.g. C6-10 aryl groups). Such groups may be monocyclic, bicyclic or tricyclic and have between 6 and 14 ring carbon atoms, in which at least one ring is aromatic. The points of attachment of aryl groups may be via any atom of the ring system. C6-14 aryl groups include, but not limited to, phenyl, naphthyl, biphenyl, fluorenyl and the like. Unless otherwise specified, the term “heteroaryl” when used herein refers to an aromatic group containing one or more heteroatom(s) (e.g. one to four heteroatoms) preferably selected from N, O and S. Heteroaryl groups that may be mentioned include, but not limited to, pyrrolyl, imidazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl (e.g. 2-pyridiyl) and the like. As used herein, represents a point of attachment. The dienophile Dienophiles useful in the present methods and compositions are alkenes or alkynes (i.e. comprise a -C=C- or -C≡C- bond, respectively). In some embodiments, the dienophile is a highly reactive participant in the inverse electron demand Diels-Alder reaction. The skilled person will understand that a dienophile which is a highly reactive participant in a IEDDA reaction is an electron-rich dienophile. In some embodiments, the dienophile is a strained dienophile. As used herein, a "strained" dienophile has a dihedral angle that deviates from the idealized 180 degree dihedral angle. By “alkenes”, we include the meaning of an alkyl group having one or more double carbon- carbon bonds such as an ethylene, propylene or other straight chain alkene. Alkenes can also include cyclic alkenes such as cyclopropene, cyclobutene, cyclopentene, cyclohexene and cyclooctene, and ring-strained alkenes such as cyclopropene, cyclobutene, trans- cyclooctene or norbornene carrying a double bond which induces significant ring strain and is thus highly reactive. Alkenes can also include more complex structures such as indoles and azaindoles, enamines (such as electron rich enamines). The skilled person will understand that when the dienophile is an alkene, the dienophile does not comprise a further double bond conjugated with said alkene (i.e. the dienophile is not also a diene). In some embodiments, the alkene is a strained alkene such as norbornene or trans- cyclooctene. In some preferred embodiments, the dienophile is an eight-membered non- aromatic cyclic alkenylene group (i.e. a non-aromatic eight-membered ring comprising a carbon-carbon double bond in the ring structure), particularly a trans-cyclooctene (TCO) group. In an embodiment, the dienophile comprises a non-aromatic 8-membered cycloalkenyl or heterocycloalkenyl ring (i.e. including one or more hetero-atoms). The skilled person is familiar with the fact that the dienophile activity is not necessarily dependent on the presence of all carbon atoms in the ring, since also heterocyclic monoalkenylene eight- membered rings are known to possess dienophile activity. Thus, in general, the invention is not limited to strictly trans-cyclooctene as a dienophile. The person skilled in organic chemistry will be aware that other eight-membered ring-based dienophiles exist, which comprise the same endocyclic double bond as the trans-cyclooctene, but which may have one or more heteroatoms elsewhere in the ring i.e., the invention generally pertains to dienophiles comprising an eight-membered non-aromatic cyclic alkenylene moieties, preferably a cyclooctene moiety, and more preferably a trans-cyclooctene moiety. Examples of TCO include TCO comprising a hydroxyl group at the 5-position, known as 5- hydroxy-trans-cyclooctene (5-OH-TCO). The skilled person will understand that when this type of TCO is used in the present invention, the TCO is attached to the surface of the cell or vesicle via the O atom of the OH group, i.e. a group present on the surface of the cell or vesicle replaces the H of the OH group of the TCO. The skilled person will also understand that the cell or vesicle may be attached to the 5-OH-TCO via a linker, i.e. the H of the OH of the TCO is replaced by a linker and the linker itself attaches to the surface of the cell or vesicle. Suitable linker moieties are defined herein. Further examples of dienophiles include those described in Figure 3 of Handula et al., Molecules. 2021 Aug; 26(15): 4640, incorporated herein by reference in its entirety. In a preferred embodiment, the dienophile is a strained dienophile. By “a strained dienophile” we include the meaning of a molecule that acts as the electron-deficient partner in a Diels-Alder reaction and contains structural features that impart significant ring strain. This strain enhances the reactivity of the dienophile, making it more susceptible to participate in the cycloaddition reaction with a diene. In a preferred embodiment, the dienophile comprises a non-aromatic eight-membered ring, such as a cyclooctene ring (CO). More preferably, the dienophile is a trans- cyclooctene (TCO) or bicyclononyne. Examples of suitable trans-cyclooctenes include conformationally strained trans- cyclooctenes such as 5-OH-TCO, d-TCO and s-TCO, and also trans-5-oxocene (oxoTCO). In certain embodiments, the dienophile is of formula (I) or formula (II) wherein X is O or N, for example X is O; when present (i.e. for formula II), ring A is a 3- to 6-membered fused cycloalkyl or 3- to 6-membered fused heterocycloalkyl ring; R1and R2are independently a direct bond or a suitable linker, wherein when the dienophile is the first click component, the cell or vesicle is attached to the dienophile via the R1or R2group (such as via any of the linker moieties comprised by the R1or R2group described below); and when the dienophile is the second click component, a detectable moiety is attached to the dienophile via the R1or R2group (such as via any of the linker moieties comprised by the R1or R2group described below). The skilled person will understand that when R1is a direct bond and the dienophile is the first click component, the X group is directly attached to the surface of the cell. Similarly, when the R1is a direct bond and the dienophile is the second click component, the X group is directly attached to the detectable moiety. The skilled person will understand that in formula II, ring A is fused with the cyclooctene ring of formula II. In some embodiments, the suitable linker comprises a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties. In some embodiments, the linker moieties are straight or branched chains comprising any combination of alkyl (e.g. C1-alkyl), alkylene, alkenyl, alkenylene chains, heterocycloalkyl, or aromatic groups (aryl and heteroaryl), and heteroatoms (e.g., -O-, -S-, -NH-, -P(O)-, - P(O)2-, etc. such as -O- and -NH-), which alkyl, alkylene, alkenyl, alkenylene, heterocycloalkyl, and aromatic groups are optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from the group consisting of, as appropriate, - OH, =O, -C(O)OH, -C(O)O(C1-4alkyl), -NH2, =NH, -C(O)NH, -C(O)N(C1-4alkyl), -SH, - C(S)(C1-4 alkyl), -S(O)2NH2, -S(O)2(C1-4 alkyl), and thiosuccinimide fragment (i.e. Particular examples of heteroaryl that may be mentioned are pyridinyl (e.g. 2-pyridinyl, 3- pyridinyl, or 4-pyridinyl), thiophenyl (e.g. 2-thiophenyl) or pyrimidinyl (e.g. 2-pyrimidinyl). In some embodiments, the linker moieties may comprise one or more ethylene glycol groups (i.e. -PEG-). Therefore, in particular embodiments, the linker may comprise or consist of from 1 to 50 -PEG- groups. In particular embodiments, the linker may comprise or consist of from 3 to 9 -PEG- groups, such as 3 -PEG- groups, 4 -PEG- groups, 5 -PEG- groups, 6 -PEG- groups, 7 -PEG- groups, 8 -PEG- groups or 9 -PEG- groups. In more particular embodiments, the linker may comprise or consist of 3 PEG groups (e.g. –(PEG)3-). In alternative particular embodiments, the linker may comprise or consist of 9 PEG groups (e.g. –(PEG)9-). In some embodiments, the linker moieties may comprise one or more amino acids (e.g. serine, leucine, glutamate, arginine, proline, alanine, asparagine, tyrosine, aspartate, valine and threonine). In more particular embodiments, each linker moiety may be independently selected from the group consisting of C1-4 alkylene (e.g. -CH2- or –(CH2)3-), C2-4 alkenylene (e.g. -CH=CH- ), -O-, -C(O)-, -NH-, -NH(O)-, -S-, -S(O)-, -S(O)2-, -(PEG)1-20- (e.g. -(PEG)1-10-, such as - Particular linker moieties that may be mentioned include -(CH2)-, -(CH2)3-, -(PEG)1-20-, - In some embodiments, the linker may comprise or consist of a moiety selected from ethylene, -(CH2)5C(O)NH(CH2)2OCH2-, -(CH2)2NH-, −(CH2)2NC(O)O-, −(CH2)2N(−CH2CH2−)2N-, -(CH2)2CH2N(−CH2CH2−)2NC(O)O-, −(CH2)2N+(CH3)2(CH2)2NH-, −(CH2)2N+(CH3)(−CH2CH2−)2N-, −(CH2)2CH2N+(CH3)(−CH2CH2−)2N-, −CH2C(O)NH(CH2)2NH-, −CH2C(O)NH(CH2)2NHC(O)-aryl-, −(CH2)2C(O)NH(CH2)2NH-, −(CH2)2SO2(CH2)3C(O)NH(CH2)2OCH2-, −CH2CC-, −CH(CF3)CH2C(O)NH(CH2)2NH-, −CH(CH2SCH3)C(O)NH(CH2)2OCH2-, −(CH2)2O(CH2)2O-, and −CH(CO2H)(CH2)2NH-. In some embodiments, the linker may comprise or consist of a moiety selected from For example, in certain embodiments, the dienophile may be selected from the group consisting of:

[0002] wherein the wavy line represents the attachment point to the surface of the cell or vesicle (when the dienophile is the first click component) or the attachment point to a detectable moiety (when the dienophile is the second click component). In some embodiments, the dienophile is an internal alkyne, terminal alkyne, or cyclic alkyne such as cyclooctyne. By “alkyne” we include the meaning of unsaturated alkyl groups (i.e. having at least one carbon–carbon triple bond). In some embodiments, the dienophile is a bicyclononyne (also known as BCN). In particular embodiments, the dienophile is a bicyclononyne of formula (III) wherein R3is a direct bond or a suitable linker (such as a linker comprising a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties), wherein when the dienophile is the first click component, the cell or vesicle is attached to the dienophile via the R3group (such as via any of the linker moieties comprised by the R3group described below); and when the dienophile is the second click component, a detectable moiety is attached to the dienophile via the R3group (such as via any of the linker moieties comprised by the R3group). The linker moieties are independently selected from the linker moieties defined with respect to R1above (including all specific embodiments thereof). Similarly, the skilled person will understand that R3may represent any of the linkers defined with respect to R1above (including all embodiments and combinations thereof). In more particular embodiments, the dienophile is a bicyclononyne selected from the group consisting of: The diene In some embodiments, the diene can be a substituted 1,2,4,5-tetrazine or other heteroaromatic ring system with at least two nitrogens adjacent to each other and which is a highly reactive participant in the inverse electron demand Diels-Alder reaction. The skilled person will understand that a diene which is a highly reactive participant in a IEDDA reaction is an electron-poor diene. Dienes useful in the present disclosure include tetrazines, such as those described in Figure 2 of Handula et al., Molecules. 2021 Aug; 26(15): 4640, incorporated herein by reference. By "tetrazine" we include the meaning of a six-membered aromatic ring containing four nitrogen atoms with the molecular formula C2H2N4, wherein one or two of the H atoms may be replaced with an R4or R5substituent as defined herein (e.g. formula (IV) below). The name tetrazine is used in the nomenclature of derivatives of this compound. Three core- ring isomers exist: 1,2,3,4- tetrazines, 1,2,3,5-tetrazines and 1,2,4,5-tetrazines. In the present invention, the tetrazine is a 1,2,4,5-tetrazine. In some embodiments, the diene may be a 1,2,4,5-tetrazine of formula (IV). wherein R4and R5may independently be: (ii) a direct bond; or (iii) a suitable linker (such as a linker comprising a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties), wherein when the diene (i.e. 1,2,4,5-tetrazine) is the first click component, the cell or vesicle is attached to the diene (i.e. 1,2,4,5-tetrazine) via the R4or R5groups (such as via any of the linker moieties comprised by the R4or R5groups described below); and when the diene (i.e. 1,2,4,5-tetrazine) is the second click component, a detectable moiety is attached to the diene via the R4or R5groups (such as via any of the linker moieties comprised by the R4or R5groups described below). The linker moieties are independently selected from the linker moieties defined with respect to R1above (including all specific embodiments thereof). The skilled person will understand that R4or R5, as appropriate, may represent any of the linkers defined with respect to R1above (including all embodiments and combinations thereof). In some embodiments, at least one of R4and R5comprises or consists of an electron- withdrawing group (e.g. -CF3). The skilled person will understand that the presence of an electron-withdrawing substituent on the 1,2,4,5-tetrazine would increase the rate of the IEDDA reaction. In particular embodiments, R5represents H,C1-12 alkyl optionally substituted by one or more fluoro (such as C1-6 or C1-4 alkyl optionally substituted by one or more fluoro, for In more particular embodiments, R5represents H or C1-6 alkyl optionally substituted by one or more fluoro (such as C1-6 or C1-4 alkyl, for example C1 alkyl i.e. methyl). In particular embodiments, R4comprises a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties selected from phenyl, pyridinyl (e.g. 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl), thiophenyl (e.g. 2-thiophenyl), pyrimidinyl (e.g. 2- pyrimidinyl), C1-4 alkylene (optionally substituted by one or more fluoro (e.g. -CH2- or – (CH2)3-)), -O-, -C(O)-, -NH-, -NH(O)-, and -S(O)2-. In more particular embodiments, R4represents -C1-6 alkyl (optionally substituted by one or In some embodiments, R4represents a suitable linker (such as defined herein) and R5represents H. In more particular embodiments, the diene is the following structure: . The skilled person will appreciate that tetrazines may comprise different electron withdrawing groups at the three and six position of the 1,2,4,5-tetrazine core (i.e. R4and / or R5are electron withdrawing groups) to increase their reactivity and at the same time ensuring modest stability in aqueous solutions, and that such tetrazines are included in the present invention. In alternative embodiments, the diene may be a 1,2,4-triazine, for example a 1,2,4-triazine as described in Kamber, Chem Sci 2019, 10, p. 9109 which is incorporated herein by reference. In alternative embodiments, the diene may be a 1,2,4-triazine, for example a 1,2,4-triazine as described in Zhang et al, Chem Rev, 2021, 121, 14555-14593 which is incorporated herein by reference. In particular embodiments, the diene may be a 1,2,4-triazine of formula (VI). wherein R8, R9and R10may independently be: (ii) a direct bond; or (iii) a suitable linker (such as a linker comprising a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties), wherein when the diene (i.e. 1,2,4-triazine) is the first click component, the cell or vesicle is attached to the diene (i.e. 1,2,4-triazine) via one of the R8or R9or R10group (such as via any of the linker moieties comprised by the R8or R9or R10groups described below, as appropriate); and when the diene (i.e. 1,2,4-triazine) is the second click component, a detectable moiety is attached to the diene via one of the R8or R9or R10groups (such as via any of the linker moieties comprised by the R8or R9or R10groups, as appropriate). The linker moieties are independently selected from the linker moieties defined with respect to R1above (including all specific embodiments thereof). The skilled person will understand that R8, R9or R10, as appropriate, may represent any of the linkers defined with respect to R1above (including all embodiments and combinations thereof). In some embodiments, at least one of (e.g. one) R8, R9and R10is or comprises (e.g. comprises) an electron-withdrawing group. The skilled person will understand that the presence of an electron-withdrawing substituent on the triazine would increase the rate of the IEDDA reaction. In particular embodiments, at least one of (e.g. one) R8, R9and R10may represent H, C1- 12 alkyl (optionally substituted by one or more fluoro (such as C1-6 or C1-4 alkyl optionally substituted by one or more fluoro, for example C1 alkyl i.e. methyl or -CF3)), In particular embodiments, at least one of (e.g. one) R8, R9and R10may represent H or C1- 6 alkyl optionally substituted by one or more fluoro (such as C1-6 or C1-4 alkyl, for example C1 alkyl i.e. methyl). In particular embodiments, at least one of (e.g. one) R8, R9and R10comprises a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties selected from phenyl, pyridinyl (e.g. 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl), thiophenyl (e.g. 2-thiophenyl), pyrimidinyl (e.g. 2-pyrimidinyl), C1-4 alkylene (optionally substituted by one or more fluoro (e.g. -CH2- or –(CH2)3-)), -O-, -C(O)-, -NH-, -NH(O)-, and -S(O)2-. In particular embodiments, at least one of (e.g. one) R8, R9and R10represents -C1-6 alkyl optionally substituted by one or more fluoro (e.g. methyl or -CF3), , In alternative embodiments, R8, R9and R10may independently be hydrogen, halogen, - OH, -N(H)C1-12alkyl, -C(O)OH, -C(O)OC1-12alkyl, -C(O)N(H)-aryl, -C(O)N(H)C1-12alkyl, optionally substituted C1-12alkyl (e.g. -CF3), optionally substituted aryl (e.g. phenyl), optionally substituted heteroaryl (e.g. pyridyl such as 2-pyridyl), -SH, -SC1-12alkyl. In particular embodiments, the 1,2,4-triazine may be selected from the group consisting of: . The linker The presence of a linker in the first click component is beneficial for the sustained presence of the click components on the cell surface. Without wishing to be bound by theory, the inventors believe that this may be due to the linker preventing or hampering internalisation of the click component, for example due to the added steric bulk of the linker. The linker may chemically stabilise the click component (for example by preventing the isomerisation of reactive trans-cyclooctene (TCO) to unreactive cis-cyclooctene (CCO)). Advantageously, the presence of a linker may therefore lead to a higher presence of the first click component on the cell or vesicle surface, thus allowing the isolated conjugate of the invention to be used for methods defined herein (e.g. detecting or directing cells or vesicles) for longer periods of time. For the avoidance of doubt, in the isolated conjugate, the linker connects the cell or vesicle to the diene or dienophile as defined herein. In the first click component reagent, the linker connects the cell- or vesicle-reactive moiety vesicle to the diene or dienophile as defined herein. In some embodiments (such as certain embodiments defined above), the first click component comprises a suitable linker. The suitable linker may be selected from the linkers defined above in respect of R1(including all embodiments thereof). For example, the suitable linker may comprise a series of 1 to 10 (for example 1 to 5, 1 to 4, or 1 to 3, such as one or two) connected linker moieties. In some embodiments, the linker moieties are straight or branched chains comprising any combination of alkyl (e.g. C1-alkyl), alkylene, alkenyl, alkenylene chains, heterocycloalkyl, or aromatic groups (aryl and heteroaryl), and heteroatoms (e.g., -O-, -S-, -NH-, -P(O)-, - P(O)2-, etc. such as -O- and -NH-), which alkyl, alkylene, alkenyl, alkenylene, heterocycloalkyl, and aromatic groups are optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from the group consisting of, as appropriate, - OH, =O, -C(O)OH, -C(O)O(C1-4 alkyl), -NH2, =NH, -C(O)NH, -C(O)N(C1-4 alkyl), -SH, - C(S)(C1-4 alkyl), -S(O)2NH2, -S(O)2(C1-4 alkyl), and thiosuccinimide fragment (i.e. Particular examples of heteroaryl that may be mentioned are pyridinyl (e.g. 2-pyridinyl, 3- pyridinyl, or 4-pyridinyl), thiophenyl (e.g. 2-thiophenyl) or pyrimidinyl (e.g. 2-pyrimidinyl). In some embodiments, the linker moieties may comprise one or more ethylene glycol groups (i.e. -PEG-). Therefore, in particular embodiments, the linker may comprise or consist of from 1 to 50 -PEG- groups. In particular embodiments, the linker may comprise or consist of between 3 and 9 -PEG- groups, such as 3 -PEG- groups, 4 -PEG- groups, 5 -PEG- groups, 6 -PEG- groups, 7 -PEG- groups, 8 -PEG- groups or 9 -PEG- groups. In more particular embodiments, the linker may comprise or consist of 3 PEG groups (e.g. –(PEG)3-). In alternative particular embodiments, the linker may comprise or consist of 9 PEG groups (e.g. –(PEG)9-). In some embodiments, the linker moieties may comprise one or more amino acids (e.g. serine, leucine, glutamate, arginine, proline, alanine, asparagine, tyrosine, aspartate, valine and threonine). In more particular embodiments, each linker moiety may be independently selected from the group consisting of C1-4 alkylene (e.g. -CH2- or –(CH2)3-), C2-4 alkenylene (e.g. -CH=CH- ), -O-, -C(O)-, -NH-, -NH(O)-, -S-, -S(O)-, -S(O)2-, -(PEG)1-20- (e.g. -(PEG)1-10-, such as - . Particular linker moieties that may be mentioned include -(CH2)-, -(CH2)3-, -(PEG)1-20-, - By “modification is carried out ex vivo” we include the meaning that the modification of the cell or vesicle surface (i.e. the covalent conjugation) takes place outside of an organism (e.g. patient). It will therefore be appreciated that the modification reaction (i.e. the covalent conjugation) is carried out on isolated cells in an external environment. By “covalently conjugated” as used herein, we include the meaning of a chemical conjugation reaction between a first click component reagent and a native biomolecule located at the surface of the cell or vesicle, so that the first click component and native biomolecule are joined by a covalent bond. In other words, the first click component reagent (and the first click component) is present extracellularly. In the context of the present invention, the native biomolecule is one that is endogenous to the cell or vesicle. By “native biomolecule” as used herein, we include the meaning of any endogenous molecule composed of smaller molecular building blocks that are the constituents of macromolecular structures situated in the extracellular membrane, in particular nucleic acids, proteins, glycans and lipids. Examples of a biomolecule include an enzyme, a (non- catalytic) protein, a polypeptide, a peptide, an amino acid, an oligonucleotide, a monosaccharide, an oligosaccharide, a polysaccharide, a glycan, a lipid and a hormone. In the context of the present invention, the native biomolecule will be of a wild type origin. In other words, the native biomolecule will not comprise any components that are synthetic or that were introduced to the cell or vesicle from an exogenous source. By "sugar" we include the meaning of a monosaccharide, for example glucose (Glc), galactose (Gal), mannose (Man) and fucose (Fuc). The term "sugar derivative" is herein used to indicate a derivative of a monosaccharide sugar, i.e. a monosaccharide sugar comprising substituents and / or functional groups. Examples of a sugar derivative include amino sugars and sugar acids, e.g. glucosamine (GlcNH2), galactosamine (GalNH2) N- acetylglucosamine (GlcNAc), N- acetylgalactosamine (GalNAc), sialic acid (Sia) which is also referred to as N-acetylneuraminic acid (NeuNAc), and N-acetylmuramic acid (MurNAc), glucuronic acid (GlcA) and iduronic acid (ldoA). A sugar without further substitution is understood to be a monosaccharide. A sugar may be further substituted with at one or more of its hydroxyl groups, and then it is understood to be a disaccharide or an oligosaccharide. A disaccharide contains two monosaccharide moieties linked together. An oligosaccharide chain may be linear or branched, and may contain from 3 to 10 monosaccharide moieties. It will be appreciated that it is a native biomolecule, such as a protein, peptide, lipid or sugar associated with the surface of the cell or vesicle that is conjugated to the first click component. In particular embodiments, the covalent conjugation is between an amino acid located at the surface of the cell or vesicle and the first click component reagent. In more particular embodiments, the direct and covalent conjugation is between a thiol group located at the surface of the cell or vesicle and the first click component reagent. Accordingly, in the first step, a cell or vesicle is modified ex vivo (using a simple bioconjugation process also referred to as “functionalisation”) with a first click component. Functionalisation of cells or vesicles (i.e. the covalent conjugation) with a first click component reagent can be achieved via a functionalisation reaction involving functional groups of native biomolecules at the surface of the cell or vesicle, such as functional groups in the membrane of the cell or vesicle. Suitable functionalisation reactions include substitution reactions (e.g. SN2), conjugate additions, among others. The first click component is therefore covalently attached to the surface of the cell or vesicle by forming a C-N (e.g. amide), C-O, C-S, etc covalent bond. By “functional group” we include the meaning of a group atoms and bonds in a molecule that is responsible for the characteristic chemical reactions of this molecule. Therefore, provided herein is also a method of generating an isolated conjugate comprising a cell or vesicle and a first click component, wherein the method comprises contacting ex vivo a cell or vesicle with a first click component reagent to form a conjugate comprising a cell or vesicle and a first click component, wherein the first click component is covalently conjugated (i.e. covalently bound) to the cell or vesicle surface, and wherein the first click component is selected from a dienophile (DP) or a diene, wherein the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4-triazine. There is also provided an isolated conjugate comprising a cell or vesicle and a first click component obtained or obtainable by the method described herein. By “contacting ex vivo” we include the meaning that the contacting of the cell or vesicle with the first click component reagent takes place outside of an organism, typically in a laboratory setting. It will therefore be appreciated that contacting is carried out on isolated cells in an external environment. In some embodiments, the method comprises a reducing step comprising treating the cell or vesicle with a reducing agent (such as tris(2-carboxyethyl)phosphine (TCEP)), optionally wherein the reducing step is carried out prior to contacting the cell or vesicle with the first click component reagent. The reducing step may be used in order to reduce disulphide bonds and thus create additional thiol groups at the surface of the cell or vesicle. Therefore, the reducing step may be used in particular in embodiments wherein the conjugation is carried out via a thiol on the surface of the cell or vesicle. In an embodiment, contacting a cell or vesicle with a first click component reagent is performed at 0-40°C, such as at room temperature (18-25°C), or at 4-8°C. In an embodiment, the cell or vesicle is contacted with a first click component reagent for less than 1 hour, such as within 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes. In an embodiment, the cell or vesicle is contacted with a first click component reagent for less than 45 minutes. In an embodiment, the cell or vesicle is contacted with a first click component reagent for less than 30 minutes. As can be seen in the accompanying Examples, the inventors surprisingly found that the first click component is covalently bound to the external surface of the cell or vesicle following contacting for less than 45 minutes. In a preferred embodiment of the method: i. the first click component reagent is a dienophile and the second click component is a diene; or ii. the first click component reagent is a diene and the second click component is a dienophile. In an embodiment, the first click component was contacted to the cell or vesicle at a concentration that does not affect cell viability. Suitable “first click component reagents” include the first click components described herein (i.e. dienes or dienophiles) further comprising a suitable group capable of being conjugated to the surface of the cell or vesicle also referred to herein as a “cell- or vesicle- reactive moiety” (i.e. to a biomolecule present on the surface of the cell or vesicle). The skilled person will understand that once the conjugation reaction occurs, i.e. a new covalent bond forms, the cell- or vesicle-reactive moiety is converted into its conjugated form. Based on the structure of the cell- or vesicle-reactive moiety, the skilled person will be able to determine the structure of the cell- or vesicle-reactive moiety conjugate, and vice versa. For instance, in some embodiments, the cell- or vesicle-reactive moiety of the first click component reagent is capable of reacting with an NH2 group, e.g., on a side chain of a lysine, the N terminus of a protein, or a membrane lipid. An example of a cell- or vesicle- reactive moiety capable of reacting with an NH2 group is an Imidoester, active ester, or Hydroxymethyl phosphine. In some embodiments, the cell- or vesicle-reactive moiety is capable of reacting with an imidazoyl (such as an imidazoyl of a histidine). An example of a cell- or vesicle-reactive moiety capable of reacting with an imidazoyl group is an active ester. In some embodiments, the cell- or vesicle-reactive moiety is capable of reacting with a carboxyl, e.g., on a side chain of aspartic acid or glutamic acid or the C-terminus of a protein. An example of a cell- or vesicle-reactive moiety capable of reacting with a carboxyl is an amine (optionally mediated by a carbodiimide such as (1-Ethyl-3-(3- dimethylaminopropyl)carbodiimide (also known as EDC)). In some embodiments, the cell- or vesicle-reactive moiety is capable of reacting with a sulfhydryl (thiol) of a protein, e.g., on a side chain of cysteine. An example of a cell- or vesicle-reactive moiety capable of reacting with a sulfhydryl is Maleimide, Haloacetyl (e.g., Bromo- or Iodo-), Pyridyldisulfide, Thiosulfonate, Vinylsulfone, or alkyl halides. The skilled person will understand that once such cell- or vesicle-reactive moieties have reacted with a thiol, the newly formed moiety may be referred to as a “thiol conjugate”, e.g. upon reacting with thiol, the cell- or vesicle- reactive moiety maleimide forms a “maleimide conjugate” (which may also be referred to as a “thiol-maleimide conjugate”). Further examples of cell- or vesicle-reactive moieties capable of reacting with a sulfhydryl (thiol) of a protein are aziridines, acryloyls, and arylation agents. In some embodiments, the cell- or vesicle-reactive moiety is selected from aziridine, acryloyl, and arylation agent. In some embodiments, the cell- or vesicle-reactive moiety is capable of reacting with a carbonyl on the cell or vesicle surface. For instance, a ketone or aldehyde group can be created in glycoproteins, e.g., by oxidizing the polysaccharide post-translational modifications, for instance with sodium meta-periodate. An example of a cell- or vesicle- reactive moiety capable of reacting with a carbonyl is a hydrazide or alkoxyamine or a ketone or aldehyde group e.g. in a glycoprotein. Particular cell- or vesicle-reactive moieties capable of being conjugated to the surface of the cell or vesicle (i.e. to a biomolecule present on the surface of the cell or vesicle) include, but are not limited to: carboxylic acids and derivatives thereof (e.g. -C(O)OR10and -C(O)Cl, wherein R10may be alkyl, aryl, or heteroaryl; isocyanate (i.e. -NCO); isothiocyanate (i.e. -NCS); thiol (i.e. -SH); a thioester (i.e. -C(O)SR11, wherein R11may be alkyl, aryl or heteroaryl); a maleimidyl group an iodoacetamidyl group In some embodiments, the first click component has been (or is) conjugated to the cell or vesicle via (i.e. using or by means of) (i) a thiol-reacting moiety present as part of the first click component reagent; and (ii) a thiol present on the surface of the cell or vesicle, to form a thiol conjugate. In some embodiments, the first click component has been (or is) conjugated to the cell or vesicle via (i.e. using or by means of) a moiety selected from maleimide, vinylsulfone, haloacetyl, pyridyldisulfide or thiosulfonate. The skilled person will understand that in such embodiments, the first click component reagent (i.e. the reagent used to conjugate the first click component to the cell or vesicle) comprises a cell- or vesicle reactive moiety selected from maleimide, vinylsulfone, haloacetyl, pyridyldisulfide and thiosulfonate. In such embodiments, the first click component is covalently conjugated to the cell or vesicle surface via (i.e. using or by means of) a conjugate of maleimide, vinylsulfone, haloacetyl, pyridyldisulfide or thiosulfonate. As used herein, the terms “maleimide” and “maleimidyl” may be used interchangeably. The skilled person will understand what chemical structures these terms refer to, based on the context. Therefore, in particular embodiments, the cell- or vesicle-reactive moieties capable of being conjugated to the surface of the cell or vesicle is a maleimide group. The skilled person will understand that in such embodiments, the first click component is conjugated to the surface of the cell or vesicle via a “thiol-maleimide conjugate”. The “thiol-maleimide conjugate” may be represented by the following formula (IA): wherein the wavy bond adjacent to the N is attached to the (remainder of) the first click component and the wavy bond adjacent to the S is attached to the (remainder of) the cell or vesicle. As discussed herein, it has been found that the presence of a linker as part of the first click component is beneficial for the sustained presence of the click components on the cell or vesicle surface. Without wishing to be bound by theory, this is believed to be because the linker might prevent or hamper internalisation of the click component. However, as can be seen from the Examples, surprisingly, the combination of a linker and the cell- or vesicle-reactive moiety being a maleimide leads to an increased tolerance of the functionalisation, i.e. the functionalised cell viability is significantly improved (see e.g. the higher viability of cells when functionalised with TCO-PEG3-maleimide vs the lower viability of the cells when functionalised with TCO-PEG3-NHS ester, as shown in Examples 1 and 2). The skilled person may determine cell or vesicle viability using any suitable methods known in the art. In some embodiments, the use of the isolated conjugate leads to increased cell or vesicle viability, such as wherein the viability is measured at around 3 days after the conjugation step. As seen in the examples, particularly good concentrations (that also lead to good visualisation of cell viability) are from 0.02 mM to 0.1 mM of the first click component reagent. The skilled person will appreciate that the optimal concentrations may be different depending on the cell type. Therefore, in some embodiments: the first click component comprises a linker (such as a linker comprising at least one -PEG- group, e.g. comprising a –(PEG)3- or –(PEG)9- group); and the first click component is covalently conjugated to the cell or vesicle surface via a thiol- maleimide conjugate (i.e. the conjugated cell isolate comprises a thiol-maleimide conjugate of formula (IA): wherein the wavy bond adjacent to the N is attached to the (remainder of) the first click component and the wavy bond adjacent to the S is attached to the (remainder of) the cell or vesicle). In particular such embodiments, the linker may be selected from (i.e. comprise or consist of any one of): In further particular embodiments, the first click component comprises: maleimide conjugate (i.e. succinate); a linker comprising or consisting of 3 to 9 –(PEG)- groups, such as –(PEG)3- or –(PEG)9-; and trans-cyclooctene (i.e. dienophile). In alternative particular embodiments, the first click component comprises: maleimide conjugate (i.e. succinate); a linker comprising or consisting of 3 to 9 –(PEG)- groups, such as –(PEG)3- or –(PEG)9-; and a 1,2,4,5-tetrazine. In alternative particular embodiments, the first click component comprises: maleimide conjugate (i.e. succinate); a linker comprising or consisting of 3 to 9 –(PEG)- groups, such as –(PEG)3- or –(PEG)9-; and bicyclo[6.1.0]nonyne (BCN). Suitable “first click component reagents” also include the first click components described herein (i.e. dienes or dienophiles) further comprising a suitable leaving group, such that a biomolecule on the surface of the cell or vesicle may essentially replace the leaving group to form a covalent bond between the first click component and the surface of the cell or vesicle (i.e. covalent bond between the first click component and a biomolecule present on the surface of the cell or vesicle). The skilled person will understand that once the covalent bond is formed, the leaving group is no longer attached to the first click component reagent. Particular leaving groups include, but are not limited to: halogen (e.g. Cl, Br, I); sulphonates such as tosylate (i.e. p-Me-Ph-SO2-); pentafluorophenyl ester; and an active ester (e.g. phenol ester or N-hydroxysuccinimide ester (NHS ester), e.g. For example, the “first click component reagents” may include TCO-NHS ester, TCO-PEG3- NHS ester, TCO-PEG3-maleimide, Tz-NHS ester or BCN-NHS ester. The structures of these reagents are shown below. It will be appreciated that alternative functional groups of native biomolecules at the surface of the cell or vesicle (for example, alcohols, carboxyls, amines, carbonyl, aldehydes, phosphates, etc.) can be functionalised with the first click component using any bioconjugation chemistry, such as those listed in Ertl, Altmann, McKenna; The Most Common Functional Groups in Bioactive Molecules and How Their Popularity Has Evolved over Time, J Med Chem 2020, 63(15), p. 8408, which is incorporated by reference in its entirety. As demonstrated in the accompanying Examples, the functionalisation of cells with click components can be obtained using a variety of functional groups of native biomolecules at the surface of the cell or vesicle. In addition, according to the accompanying Examples, the click components remained available on the membrane of a cell or vesicle following the bioorthogonal click reaction for several days. In some embodiments, conjugation of the first click component to the cell or vesicle surface can be achieved in at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours. Preferably conjugation of the first click component to the cell or vesicle surface can be achieved in less than 1 hour. In some embodiments, conjugation of the first click component to the cell or vesicle surface can be achieved in less than 1 hour, such as within 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes. As demonstrated in the accompanying Examples, the invention allows short cell handling times, which will benefit the cells’ survival and therapeutic efficacy. It will be appreciated that such a short handling time is of interest when using cells or vesicles that can only survive in laboratory conditions for short periods of time (such as less than 12 hours), for example when using primary cells such as freshly harvested lymphocytes for donor lymphocyte infusion (DLI). In an embodiment, the cell is a therapeutic cell and / or the vesicle is a therapeutic vesicle. By “therapeutic cell” we include the meaning of any cell that is intended to be administered to a subject and is suitable for use in medical purpose, such as to diagnose, treat, prevent and / or manage a disease or condition. In an embodiment, the cell is a mammalian cell. In an embodiment, the cell is derived from the same species as the subject. In an embodiment, the cell is a primary cell. By “primary cell” we include the meaning of a cell that is isolated or harvested directly from living tissue or organs. In a preferred embodiment, the cell is a stem cell or progenitor cell (such as Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs), Hematopoietic Stem Cells (HSCs)), Mesenchymal Stem Cells (MSCs) or Neural Stem Cells) or an immune cell (such as macrophages, lymphocytes, T-cells (including Chimeric Antigen Receptor T Cells (CAR- T Cells), Natural-Killer (NK) cells, NK-like T-cells or Tumor infiltrating lymphocytes (TILs), bone marrow cells, and Dendritic Cells). Therapeutic cells applicable to the present invention may include one or more selected from the group comprising: cells for regeneration (for example, stem or progenitor cells for regeneration of tissue in organs such as heart, brain, liver, kidney, lungs, pancreas etc. (such as Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs) or Neural Stem Cells)), cells for treatment of cancer (for example, T-cells (such as Chimeric Antigen Receptor T Cells (CAR-T Cells)), Natural-Killer (NK) cells, NK-like T-cells or Tumor infiltrating lymphocytes (TILs)), bone marrow cells (for example, Hematopoietic Stem Cells (HSCs)), immune cells (for example, Dendritic Cells, Donor Lymphocytes) or cells for modulation of immune responses (for example, macrophages, Mesenchymal Stem Cells (MSCs), decimal cells), Pancreatic Islet Cells or Genetically Modified Cells. It will be appreciated that the methods of the invention as described herein can be used for any type of cell that needs to be tracked or directed to a target site in a subject, but are typically therapeutic in nature. In an embodiment, the cell is autologous (i.e. is a cell originating from the subject). It will be appreciated that the cell could be modified. For example, the cell could be a CAR- T cell, or a cell that has been modified by gene editing, or a cell that comprises modified oligonucleotides. In an embodiment, the vesicle is selected from the group comprising: extracellular vesicles, organelles, exosomes, small extracellular vesicles, microvesicles, medium extracellular vesicles, liposomes and combinations thereof. In an embodiment, the vesicle is an exosome. By “exosome” we include the meaning of an extracellular vesicle generated by a cell. In some embodiments the vesicle is a synthetic vesicle. In a preferred embodiment, the vesicle is a naturally occurring vesicle. In an embodiment, the vesicle is derived from a cell, such as a mammalian cell. The mammalian cell can be a healthy or diseased mammalian cell. In an embodiment, the vesicle is derived from the same species as the subject and is therefore an autologous vesicle. The vesicle may be derived from the membrane of a tumour cell, an immune cell, a fibroblast or a bacterial cell. In an embodiment, the vesicle is derived from a primary cell. In embodiment, the vesicle is a therapeutic vesicle. By “therapeutic vesicle” we include the meaning of any vesicle that is intended to be administered to a subject and is suitable for use in medical purpose, such as to treat, prevent and / or manage disease / condition. It will be appreciated that vesicles can be useful in the treatment of many disease including for cancer immunotherapy (see Xu C. et al., Front. Immunol., 07 July 2022 Sec. Cancer Immunity and Immunotherapy Volume 13 – 2022). Methods for isolating or producing vesicles are known in the art and are described in Xu C. et al 2022). It will be appreciated that the vesicle could be modified. Modification methods include surface modification by lipid insertion, attachment of tumor-targeting peptides and / or antibodies and gene editing to allow the expression of proteins targeting tumours. In terms of modification contents, they mainly include proteins, nucleic acid aptamers, and polyethylene glycol (PEG). It will be appreciated that the hollow-core structure of vesicles allows space for the loading antitumor drugs. In a preferred embodiment, the first click component is not covalently conjugated to the cell or vesicle surface by metabolic labelling. By “metabolic labelling”, we include the meaning of a process or method in which the endogenous machinery of living cells is used to incorporate reactive click components into biomolecules. In general, this is accomplished by growing cells or organisms in media in which a specific natural substrate (e.g. amino acid, nucleotide and carbohydrate) is replaced with a close analogue bearing a chemical reporter for subsequent modification with affinity or biophysical tags. Consequently, cells use the chemical analogue instead of the natural substrate to synthesize or modify glycans, nucleic acids or proteins. Specific metabolic labelling approaches not used in the present invention include glycoengineering in which sugar chains on membrane protein are modified with different types of unnatural monosaccharide residues containing an azide group (azide sugars), such as N-azidoacetylmannosamine, N-azidoacetylglucosamine, N-azidoacetylgalactosamine and 6-azidofucose. These derivatives were incorporated into the sugar chains on the cell membrane through the intrinsic metabolic machinery, and were visualized following click ligation with fluorescent dyes. Further specific approaches not used in the present invention include genetic code expansion methods via the incorporation of non-canonical amino acids (ncAAs) during protein synthesis, by in vivo synthesis of oligonucleotides containing IEDDA bioorthogonal click components and the incorporation of methionine derivatives bearing azido or alkyne groups for the metabolic labelling of nascent proteins in living cells. Numerous bioorthogonal probes have been developed for metabolic labelling, including azidohomoanaline for labelling newly synthesized proteins, 5-ethynyl-2'- deoxyuridine (EdU) and 5-Vinyl-2'-deoxyuridine (VdU) for labelling nucleic acids, azido palmitic acid for labelling inter-membrane proteins, and azido sugars for labelling glycoproteins, approaches that use such probes are not included in the present invention. In an embodiment, the isolated conjugate comprising a cell or vesicle and a first click component further comprises a second click component, which is covalently bound to the first click component. As explained in the accompany Examples, a second click component can be provided which reacts with the first click component, such as in an IEDDA reaction to form a conjugate comprising a cell or vesicle, a first click component and a second click component. In an embodiment, the second click component comprises a detectable moiety. By “detectable moiety” as used herein, we include the meaning a moiety that is capable of visualisation when present in a cell, tissue or organism. It will be appreciated that a detectable moiety provides a detectable signal which can be measured. Accordingly, a detectable moiety can be used to visualise locally and assess and / or measure the local amount of a first click component conjugated to the surface of a cell or vesicle. The choice of detectable moiety may depend on the cell type, therapeutic goal, desired resolution, physicochemical characteristics of the second click component or imaging technique used. It will be appreciated that different detectable moieties offer advantages in terms of contrast and bioavailability. Particular examples of detectable moieties are contrast-providing moieties used in traditional imaging systems such as MRI-imageable moieties, spin labels, optical labels, ultrasound- responsive constructs, X-ray-responsive moieties, radionuclides, (bio)luminescent and FRET- type dyes. Exemplary detectable labels envisaged within the context of the present invention include, but are not necessarily limited to, fluorescent molecules (e.g. Cy5, Cy5.5, Cy7, Alexa Fluor dyes, BODIPY dyes, Coumarin dyes, Fluorescin dyes, upconversion luminescent nanoparticles (UCNPs)); Chromophores, including auxochromes and halochromes (e.g. beta-carotin, phenolphthalein, crystal violet, Orange G, Victoria Blue, Congo Red); FRET pairs (e.g. Cy2-Cy3, Alexa Fluor 647-Alexa Fluor 750, CFP-YFP, GFP-mRFP, FITC-TRITC); MRI imaging agents (e.g. comprising paramagnetic metal, Omniscan, Gd binding chelators, Iron Oxide chelators, small molecules or nanoparticles); SPECT imaging agents (e.g. 123I-MIBG, 131I-MIBG, 99mTc- HMPAO, 99mTc- tetrofosmm); Phosphorescent probes (e.g. containing ZnS, CaS, SrAl204, Ln silicates); Luminescent probes (e.g. chemimminescence, bioluminescence, electochemiluminescence, electroluminescence, crystallomuminescence, electrochemiluminescence, photoluminescence, radioluminescence, sonoluminescence, thermoluminescence); Probes that represent a key component for the generation of Luminescence (e.g. luciferin, luciferase, ATP); Enzymes, peptides or other biomolecules (fluorescent or biologically active) (e.g. GFP, RFP, Cytochrome P50, HSP90, Somatostatin, Neurotensin Y, Substance P); Quantum dots (e.g. Cadmium and Cadmium-Free Quantum dots, 1-1000 nm in size) o) Redox-active organic or organometallic complexes (e.g. Ferrocene, Ferrocenium, cobaltocene, cobaltocenium, other metals or transition metal complexes); radioactive labels; biotin, e.g., to be detected through binding of biotin by avidin. The radioactive label used for imaging can be, for example, an isotope selected from the group consisting of3H,11C,13C,13N,15O,18F,51Cr,52Fe,52Mn,55Co,60Cu,61Cu,62Zn,62Cu,63Zn,64Cu,66Ga,67Ga,68Ga,70As,71As,72As,74As,75Se,75Br,76Br,77Br,8°Br,82Br,82Rb,86Y,88Y,89Sr,89Zr,97Ru,99Tc,110In,mIn,113In,114In,117Sn,120I,122Xe,123I,1241,125I,166Ho,167Tm,169Yb,193Pt,195Pt,201Tl, and203Pb. Other elements and isotopes, such as those suitable for therapy may also be applied for imaging in certain applications. The MRI-imageable moiety can be, for example, a paramagnetic ion or a superparamagnetic particle. The paramagnetic ion can be an element selected from the group consisting of Gd, Fe, Mn, Cr, Co, Ni, Cu, Pr, Nd, Yb, Tb, Dy, Ho, Er, Sm, Eu, Ti, Pa, La, Sc, V, Mo, Ru, Ce, Dy, Tl. The ultrasound responsive moiety can comprise a microbubble, the shell of which consisting of a phospholipid, and / or (biodegradable) polymer, and / or human serum albumin. The microbubble can be filled with fluorinated gasses or liquids. The X-ray-responsive moieties include but are not limited to iodine, barium, barium sulfate, gastrografin or can comprise a vesicle, liposome or polymer capsule filled with iodine compounds and / or barium sulfate. In the context of the present invention: i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. As explained herein, click chemistry reactions occur between pairs of chemical groups that react with each other, such as first and second click component. A skilled person will appreciate that either a dienophile or a diene can be used as the first click component, and either a dienophile or a diene can be used as the second click component. As shown in the Examples described herein, click chemistry reaction can occur when the first click component is a dienophile and the second click component is a diene, or the first click component is a diene and the second click component is a dienophile. It will be further appreciated that the first click component and second click component are not identical. As can be seen in the accompanying Examples, Figure 3 demonstrates a dienophile reagent (TCO-NHS, i.e. a first click component reagent) reacting to bind TCO (i.e. a first click component) to an amine on the cell surface and detection via a radioactive tetrazine (diene; second click component); Figure 4 demonstrates a tetrazine (diene) on the cell (i.e. a first click component) and detection via a fluorescent TCO (dienophile; second click component reagent). In an aspect, the invention provides a pharmaceutical composition comprising an isolated conjugate as disclosed herein, together with a diluent, excipient or carrier, in a form suitable for administration to a subject. By “subject” we include the meaning of any animal in which treatment with a method and / or composition disclosed herein is necessary or desired. In some embodiments, the subject is any animal that can receive a beneficial and / or therapeutic effect from administration of a conjugate of the present invention. Suitable subjects include, but not are limited to, mammals. The term “mammal” as used herein includes, but is not limited to, humans, primates, non-human primates (e.g., monkeys and baboons), cattle, sheep, goats, pigs, horses, cats, dogs, rabbits, rodents (e.g., rats, mice, hamsters, and the like), etc. Human subjects include neonates, infants, juveniles, and adults. Optionally, the subject is “in need of” the methods of the present invention, e.g., because the subject has or is believed at risk for a disorder including those described herein or that would benefit from the delivery of a composition including those described herein. For example, in particular embodiments, the subject has (or has had) or is at risk for a cancer. As a further option, the subject can be a laboratory animal and / or an animal model of disease. In some embodiments, the subject is a mammal and in particular embodiments, the subject is a human of any age, race, gender, or ethnicity, etc. In some embodiments, the subject may be a human patient. In an embodiment, the pharmaceutical composition comprises other medicinal agents, pharmaceutical agents, stabilizing agents, buffers, carriers, adjuvants, or diluents, etc. For injection, the carrier will typically be a liquid. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. For other methods of administration, the carrier may be either solid or liquid. For inhalation administration, the carrier will be respirable, and will preferably be in solid or liquid particulate form. Pharmaceutical compositions suitable for parenteral administration can comprise sterile aqueous and non-aqueous injection solutions of the composition of this invention, which preparations are optionally isotonic with the blood of the intended recipient. These preparations can contain anti-oxidants, buffers, bacteriostats and solutes, which render the composition isotonic with the blood of the intended recipient. Aqueous and non- aqueous sterile suspensions, solutions and emulsions can include suspending agents and thickening agents. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like. In an aspect, the invention provides a kit comprising: a. a first click component reagent, as disclosed herein; and b. a second click component reagent selected from a dienophile (DP) or a diene, optionally wherein the second click component comprises a detectable moiety. In certain embodiments, kits are provided that may be used to carry out the methods of the invention as described herein, for example for detecting the presence and / or location of a cell or vesicle in a subject, or a method for directing a cell or vesicle to a target site in a subject, using the click chemistry components, method steps and / or reagents described herein. Accordingly, in an embodiment, the kit further comprises instructions for practicing any of the methods described herein. In an embodiment of the kit, the kit further comprises instructions for using the second click component reagent as a control, for example to allow the user to confirm that the first click component has attached to the cell or vesicle, as appropriate. In an alternative embodiment of the kit, the kit further comprises instructions for using the first click component reagent as a control, for example to allow the user to confirm that the second click component reagent has been formed and / or is active (i.e. is able to react) in a click reaction with the first click component. Optionally, in such embodiments, the first click component reagent comprises a detectable moiety. The kit may comprise a substrate comprising the first click component to which the second click component can bind. The substrate may be one or more magnetic beads or a column. In a preferred embodiment of a kit: i. the first click component reagent is a dienophile and the second click component is a diene; or ii. the first click component reagent is a diene and the second click component is a dienophile. The first click component reagent may be as defined in the first aspect of the invention (including all embodiments thereof). The second click component reagent may be as defined in the first aspect of the invention (including all embodiments thereof). As discussed in detail herein, the biggest challenge of cell-based therapies in general, is that the fate of the cells after injection is completely unknown. The inventors provide herein a novel cell tracking strategy with minimal risk of off-target effects. This capability is especially valuable in applications that involve the administration of therapeutic cells – such as immune cell therapy for cancer patients or stem cell therapy to regenerate healthy tissue. Accordingly, an aspect of the invention provides, an isolated conjugate as defined herein, or a pharmaceutical composition as defined herein, for use in detecting the presence and / or location of a cell or vesicle in a subject. An aspect of the invention provides, use of an isolated conjugate as defined herein, or a pharmaceutical composition as defined herein, in the manufacture of a medicament for detecting the presence and / or location of a cell or vesicle in a subject. An aspect of the invention provides, a method of detecting the presence and / or location of a cell or vesicle in a subject, the method comprising administering an isolated conjugate as defined herein, or a pharmaceutical composition as defined herein, to the subject. It will be appreciated that, unless stated otherwise, the definitions and descriptions provided above in relation to the previous aspects of the invention also apply to these further aspects of the invention. By “detecting the presence and / or location of a cell or vesicle in a subject” as used herein, we include the meaning of a method for observing or monitoring the existence and / or distribution and / or migration of biologically active cells in a subject via a non-invasive technology such as imaging. This is also referred to herein as “cell tracking”. The presence and / or location of the cell or vesicle may be detected and determine over a period of time in order to assess changes in the presence and / or location over that period of time (e.g. seconds, minutes, hours, days or weeks etc). The presence and / or location of the cell or vesicle in a subject may be at a detected at a single point in time (e.g. a snapshot). We include determining the presence and / or location of the cell or vesicle in one or more organs of a subject and / or determining the presence and / or location of the cell or vesicle in one or more tissues of a subject (e.g. within a particular organ). Methods for detecting the presence and / or location of a cell or a vesicle in a subject are described herein. Methods of administering cells to a subject are well known to those skilled in the art, including, e.g., as described in WO 2004 / 048557; WO 2008 / 033403; U.S. 2008 / 0279813 WO2008 / 033403; U.S. Pat. No. 7,572,631; and WO 2009 / 131712, which are all herein incorporated by reference in their entirety. The amount of cells or vesicles to be administered, for example to be effective in the prevention and / or treatment of a disease or condition, may be determined by standard clinical techniques. The dosage will depend on the type of disease to be treated, the severity and any previous therapy the recipient has undergone and / or is undergoing, the recipient's clinical history, and the discretion of the attending physician. The isolated conjugate and / or the second click component may be administered in various treatment regimens, e.g., a single or a few doses over one to several days to ameliorate symptoms and / or periodic doses over an extended time to inhibit disease progression, to reduce disease presence, and / or to prevent disease recurrence. The precise dose to be employed in the formulation will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient's circumstances. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. As shown in the accompanying Examples, detecting the presence and / or location of a cell or vesicle in a subject is performed following the addition of a second click component, which renders the isolated conjugate comprising a cell or vesicle and a first click component detectable. For example the second click component may be an imaging diene, such as a fluorescent diene for detection via optical imaging or a radio-labelled diene for detection via PET. It will be appreciated that the isolated conjugate may be contacted with the second click component ex vivo before delivery to the subject, or in vivo once it has been delivered to the subject. It will be appreciated that the choice of imaging method depends on factors such as the type of detectable moiety, the imaging resolution required, and the specific clinical or research objective. In an embodiment, before administration to the subject, the isolated conjugate is contacted ex vivo with a second click component, wherein the second click component binds covalently to the first click component ex vivo so as to make the conjugate comprising a cell or vesicle and a first click component detectable. Accordingly, it will be appreciated that the click chemistry reaction occurs outside of the subject. As such, this embodiment provides an ex vivo cell labelling technique that could be used to label the cells before administration to the subject injection (for example, for controls, or if a ‘dynamic’ scan is being performed where cells are injected while the detection if being performed on the subject so that the presence and / or location of the cells or vesicles can be detected immediately after administration). In an alternative embodiment, the isolated conjugate comprising a cell or vesicle and a first click component is administered to the subject, wherein the subject is also administered a second click component, wherein the second click component binds covalently to the first click component in the subject so as to make the conjugate comprising a cell or vesicle and a first click component detectable. It will be appreciated that the order in which the isolated conjugate comprising a cell or vesicle and a first click component, and the second click component, are administered to the subject can be determined by the skilled person. Optionally, the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component. For example, the second click component is administered to the subject 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, such as 12 hours, 15 hours, 18 hours, 20 hours, such as 1 day, 2 days, such as 3 days before the isolated conjugate comprising a cell or cellular vesicle and a first click component. Optionally, the second click component is administered to the subject with or after the isolated conjugate comprising a cell or vesicle and a first click component. Accordingly, the second click component can be administered to the subject simultaneously with the isolated conjugate comprising a cell or vesicle and a first click component. In an embodiment, the second click component is administered to the subject after the isolated conjugate comprising a cell or cellular vesicle and a first click component, such as 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, such as 12 hours, 15 hours, 18 hours, 20 hours, such as 1 day, 2 days, such as 3 days after the isolated conjugate comprising a cell or cellular vesicle and a first click component. In an embodiment, the second click component is administered to the subject after the isolated conjugate comprising a cell or cellular vesicle and a first click component, such as 4 days, 5 days, 6 days, 7 days, 10 days, 14 days, 21 days or 28 days after the isolated conjugate comprising a cell or cellular vesicle and a first click component. Accordingly, it will be appreciated that the second click component binds covalently to the first click component in vivo in the subject so as to make the conjugate comprising a cell or vesicle and a first click component detectable. In an embodiment, the conjugate comprising a cell or vesicle and a first click component is made detectable in the subject for at least 1 day, such as 2, 3, 4, 5, or 6 days. In an embodiment, the conjugate comprising a cell or vesicle and a first click component is made detectable in the subject for at least 1 day, such as 3 days, 5 days, 7 days, or 14 days. In an embodiment, the conjugate comprising a cell or vesicle and a first click component is made detectable in the subject for at least 7 days, such as 14 days, 16 days, 18 days, 20 days, such as three weeks, 24 days, 26 days, 28 days, such as a month. In an embodiment, the second click component comprises a detectable moiety. Examples of detectable moieties are provided herein. For example, radiolabelled second click component can be used to visualise the conjugate comprising a first click component and a second click component, and to promote cell apoptosis. In an embodiment, detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject is carried out after the clearance of excess isolated conjugate comprising a cell and a first click component and / or excess second click component By “clearance of the excess second click component” as used herein, we include the meaning of the reduction or removal from the subject of any second click components which are unbound (or unused) to the conjugate comprising a cell or vesicle and a first click component. In the context of the invention, clearance will typically occur from the bloodstream or the extracellular space. It will be appreciated that following administration to the subject, not all second click component may bind to the conjugate comprising a cell or cellular vesicle and a first click component. As such, it may be advantageous to allow for the reduction or removal unbound second click components from the subject to enable high contrast imaging. In an embodiment, the subject is administered a clearing agent and / or a masking agent. By “clearing agent” we include the meaning of a substance or compound used to remove excess or non-specifically bound conjugates comprising a cell or vesicle and a first click component from the subject before the administration of the second click component- conjugated imaging agents. It will be appreciated that after the conjugate comprising a cell or vesicle and a first click component has been administered, a clearing agent may be administered that removes any first click component that is still present in the blood circulation. The clearing agent effectively removes these unbound or loosely bound first click component from circulation or other compartments, reducing background signal and improving the target-to- background ratio. Once the clearance phase is complete and background signal has been minimized, the second click component may be administered. Hydrophilic molecules, such as sugars (e.g., glucose or sucrose), amino acids (e.g., lysine), or polyethylene glycol (PEG) derivatives, can be used as clearing agents. These molecules are typically water-soluble and can effectively compete with TCO for binding to tetrazine, thereby displacing or clearing unbound TCO from the system. Dendrimeric or polymeric structures bearing sugar moieties such as dextrans or N-acetylgalactosamines (GalNAc) can be used. Dextrans are branched polysaccharides consisting of many glucose molecules tethered through α-1,4 or α-1,6 linkages, forming chains of varying lengths. Clearing agents based on polymeric dextrans typically have molecular weights of ~200–500 kDa. These large structures can bind to the circulating first click component in the blood and induce excretion via the liver. The excretion proceeds through recognition and catabolism by the reticuloendothelial system. Small molecules with high affinity for tetrazine, such as tetrazine derivatives or other reactive compounds, can be used as clearing agents. These molecules can rapidly react with unbound tetrazine, forming stable adducts and effectively removing excess tetrazine from the system. Proteins, such as bovine serum albumin (BSA) or serum proteins, can also serve as clearing agents by binding to unbound tetrazine molecules and facilitating their clearance from the circulation. Additionally, antibodies or antibody fragments specific to tetrazine can be used as clearing agents to selectively remove unbound tetrazine from the system. By “masking agent” we include the meaning of a substance or compound that aims to mask the first click component solely in the blood. Consequently, second click components cannot bind to them in the blood. It will be appreciated that the masking agents cannot interact with the first click component located at the target site. This can be achieved by designing masking agents that cannot penetrate easily into the tumor vasculature. The choice of clearing agent depends on various factors, including the specific application, the nature of the click chemistry agents, and the biological system under investigation. Clearing agents and / or masking agents should be selected based on their compatibility with the detectable agents and their ability to efficiently remove excess tetrazine while minimizing non-specific interactions and toxicity. In some embodiments, the subject is administered a clearing agent and / or masking agent before the subject is administered the second click component, such as 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes, 210 minutes, 240 minutes, 270 minutes, 300 minutes, 330 minutes, 360 minutes, 390 minutes, or 480 minutes or more before the subject is administered the second click component. In an embodiment: i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. In an aspect, the invention provides a method of detecting the presence and / or location of a cell or vesicle in a subject, the method comprising i. contacting ex vivo a cell or vesicle with a first click component reagent to form a conjugate comprising a cell or vesicle and a first click component, wherein the first click component is covalently conjugated to the cell or vesicle surface; ii. in vivo administration to a subject of the of conjugates; iii. in vivo administration of a second click component comprising a detectable moiety, under conditions such that at least a portion of the administered second click component reacts with at least a portion of the conjugate so as to make the conjugate comprising a cell or vesicle and a first click component detectable; and iv. imaging the detectable conjugate comprising a cell or vesicle and a first click component; wherein the first click component is selected from a dienophile (DP) or a diene, wherein the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4- triazine. The disclosed conjugates of the invention may be formulated as desired using art- recognized techniques. In some embodiments, the reagents and / or components of the invention may be administered neat or with a minimum of additional components while others may optionally be formulated to contain suitable pharmaceutically acceptable carriers (e.g., vehicles, adjuvants, and diluents) comprising excipients and auxiliaries that are well known in the art, including for example, pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents, radioprotectants and the like. Certain non- limiting exemplary carriers include saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. Certain non-limiting exemplary radioprotectants include ascorbic acid, gentisic acid, ethanol and combinations thereof. By “administering” as used herein we include the meaning of contacting or dispensing, delivering or applying an agent to a subject by any suitable route for delivery of the agent to the desired location in the subject, including delivery by either the parenteral or oral route, intramuscular injection, subcutaneous / intradermal injection, intravenous injection, intrathecal administration, buccal administration, transdermal delivery, topical administration, and administration by the intranasal or respiratory tract route. The particular dosage regimen for administering conjugates of the invention, i.e., dose, timing and repetition, will depend on the particular subject and that subject’s medical history, as well as empirical considerations such as pharmacokinetics (e.g., half-life, clearance rate, etc.). Frequency of administration may be determined and adjusted over the course of therapy. A therapeutically effective dose is a dose sufficient to provide a clinical benefit to the subject, including for example, a dose sufficient to reduce tumor size, maintain a reduction of tumor size, reduce or slow tumor growth, delay the development of metastasis, improve longevity, etc. Dosage administered may be adjusted or attenuated to manage potential side effects and / or toxicity. Subjects are as defined herein. In some embodiments, the subject may be a human patient. An effective amount may be administered in a single dose or multiple doses. For imaging applications, an effective amount is an amount of the disclosed detectable conjugate that results in measurable in vivo detection following administration to a subject, with sufficient sensitivity to assess biodistribution of the detectable conjugate above any background or nonspecific detection. Any detection technique known in the art may be used, for example, SPECT / CT imaging, PET, PET / CT, and PET / MRI. It will be appreciated that the present invention provides a novel and advantageous method for specific directing cells (homing) to target location in vivo. In many prior art methods, a bispecific antibody is used that binds to tumour cells via a tumour cell antigen and simultaneously binds to a T cell (e.g. via the CD3 Receptor) and recruits the T cell to the tumor area. However, this approach is based upon biological interactions, which may suffer from cross-reactivity, which increases the risk of side-effects and decreases therapeutic specificity. In an aspect, the invention provides an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical composition thereof, for use in directing a cell or vesicle to a target site in a subject, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to direct the conjugate comprising a cell or vesicle and a first click component to the target site in the subject. In an aspect, the invention provides use of an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical composition thereof, in the manufacture of a medicament for directing a cell or vesicle to a target site in a subject, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to direct the conjugate comprising a cell or vesicle and a first click component to the target site in the subject. In an aspect, the invention provides a method of directing a cell or vesicle to a target site in a subject, the method comprising administering an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical composition thereof, to the subject, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to direct the conjugate comprising a cell or vesicle and a first click component to the target site in the subject. Preferably, the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component. Optionally, the second click component is administered to the subject after the isolated conjugate comprising a cell or vesicle and a first click component. In an embodiment, the second click component is covalently attached to a targeting molecule. By “targeting molecule” we include the meaning of any substance or compound that bind specifically to a target site within the subject. By “target site” we include the meaning of specific biological structures or molecules (e.g. biomarkers or receptors) within the subject to which the targeting molecule is designed to bind. Accordingly, following administration, the targeting molecule circulates in the body and selectively binds to target biomarkers or receptors on the surface of cells or tissues (e.g. tumour cells or tissues). It will be appreciated that target site within a subject can be any cell, tissue, organ, or groups of tissues or organs. By way of a non-limiting example, the target site within a body can be epithelial tissue, connective tissue, muscle tissue, nervous tissue, heart, lungs, liver, kidneys, brain, skin, stomach, pancreas, spleen, intestines, bladder, uterus, ovaries, testes, etc. The targeting molecule may bind to biomarkers or receptors overexpressed on the surface of tumor cells. The targeting molecule may bind to the angiogenic vasculature surrounding tumors. The targeting molecule may bind to markers of angiogenesis, such as vascular endothelial growth factor receptor (VEGFR), integrins, or other endothelial cell markers. The targeting molecule may bind to inflammatory lesions by binding to specific markers of inflammation, such as adhesion molecules or cytokine receptors. The targeting molecule can also target specific organs or organ systems within the body. For example, in cardiovascular imaging, pre-targeting agents may bind to markers of cardiac injury or endothelial dysfunction for the detection of myocardial infarction or atherosclerosis. The targeting molecule can also target pathogens or infectious agents within the body. The targeting molecule may bind to specific surface antigens or proteins expressed by the pathogen, allowing for the detection or clearance of infectious agents. The targeting molecule can target specific cell types within heterogeneous populations. For example, in stem cell therapy, the targeting molecule can be designed to bind to markers specific to injured tissue, such as injured heart tissue following a myocardial infarction or injured lung or brain tissue following a stroke. The targeting molecule can target cytokines such as PDGF or VEGF or immune cells involved in wound healing, e.g. via cell surface receptors. In an embodiment, the targeting molecule specifically binds to its target. A targeting molecule that “specifically binds” or “preferentially binds” to its target, for example to a tumor or to a cancer cell, is a term well understood in the art, and methods to determine such specific or preferential binding are also well known in the art. A molecule is said to exhibit “specific binding” or “preferential binding” if it reacts or associates more frequently, more rapidly, with greater duration and / or with greater affinity with a particular target cell or molecule than it does with alternative cells or molecules. A targeting molecule “specifically binds” or “preferentially binds” to a target or antigen if it binds with greater affinity, avidity, more readily, and / or with greater duration than it binds to other molecules. Preferably, targeting molecules used in the invention have high binding affinity, for example, having a dissociation constant KD (koff / kon) of about 10-9M or less. In an embodiment, the targeting molecule binds to a tumor-associated antigen or receptor and / or a tumor-specific antigen or receptor. By “tumor-associated antigen or receptor” we include the meaning of an antigen or receptor that is found at elevated levels in tumor cells, but that may also be expressed at lower levels in non-tumor cells. By “tumor-specific antigen or receptor” we include the meaning of an antigen or receptor that is only found, or mostly found, in cancer cells. Numerous tumor targeting proteins / peptides, tumor- associated antigens and receptors, and tumor-specific antigens and receptors are known in the art and routinely used. Non-limiting examples of tumor-associated antigens or receptors and / or a tumor-specific antigens or receptors include Carcinoembryonic Antigen (CEA), Prostate-Specific Antigen (PSA), Human Epidermal Growth Factor Receptor 2 (HER2), Epidermal Growth Factor Receptor (EGFR), Programmed Death-Ligand 1 (PD-L1), Melanoma-Associated Antigen (MAGE), Mucin Antigens (e.g., MUC1), Alpha-Fetoprotein (AFP), MUC1 (Mucin 1), PSMA (Prostate-Specific Membrane Antigen), NY-ESO-1 (New York Esophageal Squamous Cell Carcinoma-1), Glypican-3 (GPC3), Survivin, WT1 (Wilms Tumor 1), HER2 / neu (Human Epidermal Growth Factor Receptor 2), CA-125 (Cancer Antigen 125), CA-15-3 (Cancer Antigen 15-3), CA-19-9 (Cancer Antigen 19-9), CEA (Carcinoembryonic Antigen), Ganglioside GD2, PRAME (Preferentially Expressed Antigen in Melanoma), CD19, CTLA-4 (Cytotoxic T-Lymphocyte Associated Protein 4), and Melan-A / MART-1. Optionally, the targeting molecule is selected from the group comprising antibodies or antigen binding fragments thereof, proteins, aptamers, oligopeptides, oligonucleotides, oligosaccharides, as well as peptides, peptoids and organic drug compounds. Exemplary targeting molecules include antibodies. “Antibodies” are immunoglobulin molecules that recognize and bind to a specific target or antigen, such as a carbohydrate, polynucleotide, lipid, polypeptide, etc., through at least one antigen recognition site, located in the variable region of the immunoglobulin molecule. By “antibody” we include the meaning of any type of antibody, including but not limited to canonical antibodies, monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, heteroconjugate antibodies, recombinantly produced antibodies, humanized antibodies, chimeric antibodies, monovalent antibodies, multivalent antibodies, anti- idiotypic antibodies, antibody fragments (described further below), and fusion proteins having an antibody or antigen-binding fragment thereof, maxibodies, minibodies, intrabodies, diabodies, triabodies, tetrabodies, and any other modified configuration of the immunoglobulin molecule including glycosylation variants of antibodies, amino acid sequence variants of antibodies, and covalently modified antibodies. Canonical antibodies comprise two heavy (H) and two light (L) polypeptide chains held together by covalent disulfide bonds and non-covalent interactions. Each light chain is composed of one variable domain (VL) and one constant domain (CL). Light chains of the antibodies from any vertebrate species can be assigned to one of two clearly distinct types, called kappa (κ) and lambda (λ), based on the amino acid sequences of their constant domains. Each heavy chain comprises one variable domain (VH) and a constant region, which in the case of IgG, IgA, and IgD antibodies, comprises three domains termed CH1, CH2, and CH3 (IgM and IgE have a fourth domain, CH4). An “antibody fragment" comprises at least a portion of an intact antibody sufficient to function as a targeting molecule as described herein. An antibody fragment generally includes an “antigen-binding fragment” which refers to a polypeptide fragment of an immunoglobulin or antibody that specifically binds or reacts with a selected antigen, target, or immunogenic determinant thereof, or that competes with the intact antibody from which the fragments were derived for specific antigen binding. Antibody fragments include, but are not limited to, a Fab fragment, a Fab’ fragment, a F(ab’)2 fragment, a Fd fragment, a Fv fragment, a Fc fragment, a scFv fragment, Fc fusions including nanobody-Fc fusions, a dual variable domain (DVD) Fab, single chain antibodies, single domain antibodies (sdAbs, also known as nanobodies and VHH antibodies, for example, VNAR antibodies). In an embodiment, the method further comprises detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject. In an embodiment, detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject is carried out after the clearance of excess second click component. In an embodiment, the subject is administered a clearing agent and / or masking agent as defined herein. In an embodiment, i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. In an aspect, the invention provides an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical composition as defined herein, for use in medicine. In an aspect, the invention provides an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical composition as defined herein, for use in treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell or vesicle to a subject. In an aspect, the invention provides use of an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical composition as defined herein, in the manufacture of a medicament for treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell or vesicle to a subject. In an aspect, the invention provides, a method of treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell or vesicle, the method comprising administering an isolated conjugate comprising a cell or vesicle and a first click component as defined herein, or a pharmaceutical as defined herein, to a subject. By “a disease or condition treatable and / or preventable by administration of a cell or vesicle to a subject” we include the meaning of any disease or condition that is treatable by a therapeutic cell or therapeutic vesicle, such as those described herein. Examples of such diseases and condition include but are not limited to blood disorders such as leukaemia, lymphoma, and myeloma, as well as inherited disorders like sickle cell anaemia and thalassemia where stem cell transplants, particularly hematopoietic stem cell transplantation; neurological disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, spinal cord injury where stem cells are being investigated for their potential to repair or replace damaged cells in the brain and spinal cord; orthopaedic injuries and degenerative conditions affecting bones, cartilage, and joints, such as osteoarthritis and injuries to ligaments and tendons; cardiovascular diseases such as such as heart failure, myocardial infarction (heart attack), and peripheral arterial disease where Stem cells can repair damaged heart tissue and improve heart function in conditions; autoimmune diseases such as rheumatoid arthritis, lupus, and Crohn's disease; Diabetes where stem cell can replace the damaged or destroyed pancreatic beta cells responsible for producing insulin; eye diseases such as macular degeneration and retinitis pigmentosa, where stem cells are being investigated for their potential to repair damaged retinal cells and restore vision; liver diseases such as cirrhosis and liver failure, where stem cell therapy can replace damaged liver tissue and promote regeneration; skin disorders including burns, wounds, and conditions like epidermolysis bullosa; immune system disorders such as severe combined immunodeficiency (SCID) and other primary immunodeficiency diseases. Therapeutic cells are used in cell therapy, including adoptive cell therapy, which has shown promising results in the treatment of cancer, such as Hematologic Cancers, including Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Chronic Lymphocytic Leukemia (CLL), Chronic Myeloid Leukemia (CML), Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Multiple Myeloma; Solid Tumors including Melanoma, Sarcoma, Renal Cell Carcinoma, Ovarian Cancer, Breast Cancer, Prostate Cancer, Colorectal Cancer, Lung Cancer, Glioblastoma (Brain Cancer). By “treatment,” and / or “therapy” we include the meaning of the clinical intervention made in response to a disease, disorder or physiological condition manifested by a subject or to which a subject may be susceptible. The aim of treatment includes the alleviation or prevention of symptoms, slowing or stopping the progression or worsening of a disease, disorder, or condition and / or the remission of the disease, disorder or condition. By “prevent,” “preventing,” “prevention,” “prophylactic treatment” as used herein, we include the meaning of reducing the probability of developing a disease, disorder or condition in a subject, who does not have, but is at risk of or susceptible to developing a disease, disorder or condition. In the context of cancer, desired therapeutic effects also include reduction of tumor size, slowing of tumor growth, decreased or slowing of metastasis, decreased tumorigenicity, decreased or amelioration of symptoms or indicators / biomarkers associated with cancer, etc. In an embodiment, the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to direct the conjugate comprising a cell or vesicle and a first click component to the target site in the subject. In an embodiment, the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component. In an embodiment, the second click component is administered to the subject after the isolated conjugate comprising a cell or vesicle and a first click component. In an embodiment, the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component. In an embodiment, the second click component is covalently attached to a targeting molecule as defined herein. The first click component may be as defined in the first aspect of the invention (including all embodiments thereof). The second click component may be as defined in the first aspect of the invention (including all embodiments thereof). In an aspect, the invention provides an isolated conjugate, a pharmaceutical composition, or a kit, substantially as hereinbefore described with reference to any one of the Examples, or to any one of the accompanying Figures. Embodiments of the invention are set out in the following numbered paragraphs. Paragraph 1. An isolated conjugate comprising a cell or vesicle and a first click component, wherein the first click component is covalently conjugated to the cell or vesicle surface, wherein the first click component is selected from a dienophile (DP) or a diene, and wherein the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4- triazine, optionally wherein the covalent conjugation is carried out ex vivo. Paragraph 2. An isolated conjugate according to Paragraph 1, wherein the dienophile is a strained dienophile. Paragraph 3. An isolated conjugate according to Paragraph 1, wherein the dienophile comprises a non-aromatic eight-membered ring, such as a cyclooctene ring (CO). Paragraph 4. An isolated conjugate according to any one of the preceding paragraphs, wherein the dienophile is a trans-cyclooctene (TCO) or bicyclononyne. Paragraph 5. An isolated conjugate according to any of the preceding paragraphs, wherein the cell is a therapeutic cell and / or the vesicle is a therapeutic vesicle. Paragraph 6. An isolated conjugate according to any of the preceding paragraphs, wherein the cell is a stem cell or progenitor cell (such as Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs), Hematopoietic Stem Cells (HSCs)), Mesenchymal Stem Cells (MSCs) or Neural Stem Cells) or an immune cell (such as macrophages, lymphocytes, T-cells (including Chimeric Antigen Receptor T Cells (CAR-T Cells), Natural-Killer (NK) cells, NK-like T-cells or Tumor infiltrating lymphocytes (TILs), bone marrow cells, and Dendritic Cells). Paragraph 7. An isolated conjugate according to any of the preceding claims, wherein the first click component is not covalently conjugated to the cell or vesicle surface by metabolic labelling. Paragraph 8. An isolated conjugate comprising a cell or vesicle and a first click component according to any of Paragraphs 1-7, further comprising a second click component, which is covalently bound to the first click component. Paragraph 9. An isolated conjugate comprising a cell or vesicle and a first click component according to Paragraph 8, wherein the second click component comprises a detectable moiety. Paragraph 10. An isolated conjugate according to Paragraphs 8 or 9, wherein i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. Paragraph 11. A pharmaceutical composition comprising an isolated conjugate as defined in any of Paragraphs 1-10, together with a diluent, excipient or carrier, in a form suitable for administration to a subject. Paragraph 12. A kit comprising: a. an isolated conjugate comprising a cell or vesicle and a first click component, as defined in any of Paragraphs 1-7; and b. a second click component selected from a dienophile (DP) or a diene, optionally wherein the second click component comprises a detectable moiety. Paragraph 13. The kit according to Paragraph 12, wherein i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. Paragraph 14. A method of generating an isolated conjugate comprising a cell or vesicle and a first click component, wherein the method comprises contacting ex vivo a cell or vesicle with a first click component reagent to form a conjugate comprising a cell or vesicle and a first click component, wherein the first click component is covalently conjugated to the cell or vesicle surface, and wherein the first click component is selected from a dienophile (DP) or a diene, wherein the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4-triazine. Paragraph 15. An isolated conjugate comprising a cell or vesicle and a first click component obtained or obtainable by the method of Paragraph 14. Paragraph 16. An isolated conjugate as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, for use in use in detecting the presence and / or location of a cell or vesicle in a subject. Paragraph 17. Use of an isolated conjugate as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, in the manufacture of a medicament for detecting the presence and / or location of a cell or vesicle in a subject. Paragraph 18. A method of detecting the presence and / or location of a cell or vesicle in a subject, the method comprising administering an isolated conjugate as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, to the subject. Paragraph 19. The isolated conjugate comprising a cell or vesicle and a first click component for use according to Paragraph 16, the use according to Paragraph 17, or the method according to Paragraph 18, wherein the isolated conjugate is as defined in any of Paragraphs 1-7. Paragraph 20. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 19, wherein before administration to the subject, the isolated conjugate is contacted ex vivo with a second click component, and wherein the second click component binds covalently to the first click component ex vivo so as to make the conjugate comprising a cell or vesicle and a first click component detectable. Paragraph 21. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 19, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to make the conjugate comprising a cell or vesicle and a first click component detectable. Paragraph 22. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 21, wherein the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component. Paragraph 23. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 21, wherein the second click component is administered to the subject after the isolated conjugate comprising a cell or vesicle and a first click component. Paragraph 24. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to any of Paragraphs 20-23, wherein the conjugate comprising a cell or vesicle and a first click component is made detectable in the subject for at least 1 day, such as 3 days, 5 days, 7 days, or 14 days. Paragraph 25. The isolated conjugate comprising a cell and a first click component for use, the use, or the method according to any of Paragraphs 20-24, wherein the second click component comprises a detectable moiety. Paragraph 26. The isolated conjugate comprising a cell and a first click component, the kit, or the isolated conjugate comprising a cell and a first click component for use, the use, or the method according to any one of Paragraphs 21-25, wherein detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject is carried out after the clearance of excess isolated conjugate comprising a cell and a first click component and / or excess second click component. Paragraph 27. The isolated conjugate comprising a cell and a first click component for use, the use, or the method according to any one of Paragraphs 21-26, wherein the subject is administered a clearing agent. Paragraph 28. The isolated conjugate comprising a cell and a first click component for use according to any one of Paragraphs 16 and 19-27, the use according to any one of Paragraphs 17 and 19-27, or the method according to any one of Paragraphs 18-27, wherein i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. Paragraph 29. An isolated conjugate as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, for use in directing a cell or vesicle to a target site in a subject. Paragraph 30. Use of an isolated conjugate as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, in the manufacture of a medicament for directing a cell or vesicle to a target site in a subject. Paragraph 31. A method of directing a cell or vesicle to a target site in a subject, the method comprising administering an isolated conjugate as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical as defined in Paragraph 11, to the subject. Paragraph 32. The isolated conjugate comprising a cell or vesicle and a first click component for use according to Paragraph 29, the use according to Paragraph 30, or the method according to Paragraph 31, wherein the isolated conjugate is as defined in any of Paragraphs 1-7. Paragraph 33. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 32, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to direct the conjugate comprising a cell or vesicle and a first click component to the target site in the subject. Paragraph 34. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 33, wherein the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component. Paragraph 35. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to Paragraph 34, wherein the second click component is covalently attached to a targeting molecule. Paragraph 36. The isolated conjugate for use, the use, or the method according to Paragraph 35, wherein the targeting molecule is selected from the group comprising antibodies or antigen binding fragments thereof, proteins, aptamers, oligopeptides, oligonucleotides, oligosaccharides, as well as peptides, peptoids and organic drug compounds. Paragraph 37. The isolated conjugate comprising a cell or vesicle and a first click component for use, the use, or the method according to any of Paragraphs 29-36, further comprising detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject. Paragraph 38. The isolated conjugate comprising a cell and a first click component for use, the use, or the method according to Paragraph 37, wherein detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject is carried out after the clearance of excess second click component. Paragraph 39. The isolated conjugate comprising a cell and a first click component for use, the use, or the method according to Paragraph 37 or 38, wherein the subject is administered a clearing agent. Paragraph 40. The isolated conjugate comprising a cell and a first click component for use according to any one of Paragraphs 29 and 32-39, the use according to any one of Paragraphs 30 and 32-39, or the method according to any one of Paragraphs 31-39, wherein: i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile. Paragraph 41. An isolated conjugate comprising a cell or vesicle and a first click component as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, for use in medicine. Paragraph 42. An isolated conjugate comprising a cell or vesicle and a first click component as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical composition as defined in Paragraph 11, for use in treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell or vesicle to a subject. Paragraph 43. Use of an isolated conjugate comprising a cell or vesicle and a first click component as defined in any of Paragraphs 1-10, and 15 or a pharmaceutical composition as defined in Paragraph 11, in the manufacture of a medicament for treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell or vesicle to a subject. Paragraph 44. A method of treating and / or preventing a disease or condition treatable and / or preventable by administration of a cell or vesicle, the method comprising administering an isolated conjugate comprising a cell or vesicle and a first click component as defined in any of Paragraphs 1-10 and 15, or a pharmaceutical as defined in Paragraph 11, to a subject. Paragraph 45. An isolated conjugate comprising a cell or vesicle and a first click component, a pharmaceutical composition, or a kit, substantially as hereinbefore described with reference to any one of the Examples, or to any one of the accompanying Figures. Embodiments of the invention will now be described, by way of example only, with reference to the accompanying figures, in which: Figure 1 shows the schematic overview of the cell tracking aspect of the invention, based on bio-orthogonal click chemistry. 1) Injection or transplantation of a conjugate composed of cells or vesicles functionalised with a dienophile (DP), 2) accumulation and / or retention at the target site, 3) Injection of fast-clearing diene, such as 1,2,4,5-tetrazine (Tz) or 1,2,4-triazine, with detectable moiety, 4) in situ click reaction between diene and DP- functionalised cell or vesicle, 5) fast clearance of the diene results in high specificity and minimal off-target signal or dose. Figure 2 shows the schematic overview of the cell homing aspect of the invention, based on bio-orthogonal click chemistry. 1) Injection of targeting molecule (e.g. an antibody), functionalised with a dienophile (DP), 2) accumulation at the target site, 3) Injection of diene-functionalised cells or vesicles, 4) in situ click reaction between DP-functionalised targeting molecule and diene-functionalised cell or vesicle. Figure 3 Cell viability is unaffected after binding with click components at low quantities. At higher quantities (≧ 1.48 nmol for TCO-NHS ester, ≧ 0.09 nmol for TCO-PEG3-NHS ester and BCN-NHS ester, ≧ 0.18 nmol for TCO-PEG3-maleimide and Tz-NHS ester), cell viability goes down. Figure 4 Higher click component (click component A (CCA) = TCO) concentrations result in higher binding of the fluorescent click component (Tz) after multiple days. Figure 5 Cells can be functionalised with click components (e.g. TCO, BCN) via different functional groups at the cell surface, for example amines (e.g. using NHS esters, (iso)thiocyanates) or thiols (e.g. using maleimides). The addition of a linker between cell surface and click component (e.g. PEG3) may improve binding to the imaging click component (in this case, radioactive Tz). Figure 6 Cells can be functionalised will different types of click components, including but not limited to, TCO (= CCA), Tz (=CCB), azide (=CCD), and BCN (=CCC), which remain available at the cell surface for multiple days for their click reaction with fluorescent Tz, TCO, Tz and azide, respectively. Figure 7 A saturation binding assay after day 1 demonstrated that the click components (TCO) at the cell surface could be saturated by the imaging click component (CCB = Tz), confirming that the binding was specific. Figure 8 shows that cells can be functionalised with click components without affecting cell viability up until a maximum concentration (Example 2). Figure 9 shows that click components at the cell surface remain available for the click reaction for multiple days (Example 2). Figure 10 hMSCs functionalised with TCO-PEG3-maleimide injected in A) heart muscle and B) left kidney (white arrows) could be detected after 3 hours by PET imaging, using an18F- labelled 1,2,4,5-tetrazine. Example 1 Cells can be functionalised with click components using simple bioconjugation chemistry without affecting cell viability Cells can be functionalised with click components (either DP or diene) without affecting cell viability up until a maximum concentration. For the MOLM-14 cells tested here, the maximum click component (TCO) concentration that could be used without affecting cell viability was 0.05 g / L. It may be assumed that other types of cells can be functionalised with click components similarly up until a maximal concentration (Figure 3). TCO-NHS: 0.74 mmol / mL, TCO-PEG3-NHS: <0.09 mmol / mL, TCO-PEG3-maleimide: 0.09 mmol / mL, Tz-NHS: 0.09 mmol / mL, BCN-NHS: 0.09 mmol / mL. The click component remains available at the cell surface for multiple days Click components at the cell surface remain available for the click reaction for multiple days. This is a crucial finding, because it was previously unknown and impossible to predict if the click component would be internalised and / or degraded and, as such, would no longer be available for binding. By increasing the click component concentration, its availability for the click reaction at the cell surface is also increased. Here, the availability of TCO, TCO-PEG3, and BCN at the cell surface was demonstrated after several days by flow cytometry using fluorescent Tz or by gamma counting using radiolabelled Tz. Depending on the click component (i.e. DP) used, any other diene (e.g. Tz, azide, etc.) could be used for imaging and detection (Figures 4, 5, 6). Cells can be functionalised with click components using simple bioconjugation chemistry based on various functional groups commonly found at the cell surface Functionalisation of cells with click components (either DP or diene) can be achieved via different functional groups at the cell surface with sustained availability for the bioorthogonal click reaction up to several days. For example, amine groups or thiol groups at the cell surface can be reacted to click components using succinimidyl (NHS) ester or maleimide, respectively. It may reasonably be assumed that alternative functional groups at the cell surface (e.g. alcohols, carboxyls, aldehydes, etc.) can be functionalised with click components using similar bioconjugation chemistry. Linkers, for example based on poly(ethylene glycol) (PEG) or other, may be used to enhance the efficacy of the click reaction up to several days. Here, the availability of TCO reacted to amines (via NHS ester) or thiols (via maleimide) at the cell surface was demonstrated after several days by gamma counting using radioactive Tz (Figures 3, 5). Cells can be functionalised with different types of click components using simple bioconjugation chemistry with sustained availability at the cell surface Cells can be functionalised with a variety of click components, which all appear to remain available at the cell surface for multiple days (Figures 3, 4, 5, 6). As described above, TCO at the cell surface remains available for binding with fluorescent Tz for multiple days. Similarly, but vice versa, Tz at the cell surface remains available for binding with fluorescent TCO. These data make it plausible that cell homing can indeed be performed using for example a tumour-targeting monoclonal antibody functionalised with TCO. The use of a TCO-functionalised monoclonal antibody, to be targeted by a Tz for imaging or therapy, is a standard and proven procedure in pretargeted imaging and therapy (Oliveira, B. L et al., Chem. Soc. Rev. 2017). Here, we suggest to use Tz-functionalised cells instead for homing and pretargeted immunotherapy. It may be noted that a linker between TCO and antibody may be required for adequate cell homing, since it has been shown that linker length accounts for flexibility and stability, and may aid the orientation of binding interaction between antibody and click component (Simão, D. C. et al., Bispecific T-Cell Engagers Therapies in Solid Tumors: Focusing on Prostate Cancer Cancers (Basel) [Online], 2023). Interestingly, the use of BCN instead of TCO improved binding of the fluorescent Tz after several days with several orders of magnitude. Click components at the cell surface can be saturated To demonstrate that binding of the imaging click component (i.e. Tz) was specific, we performed a saturation binding assay (Figure 7). This assay demonstrated that click components at the cell surface (i.e. TCO) could indeed be saturated (KD = 0.65 nM). Materials and Methods Human leukaemia MOLM-14 cells were used, which are commercially available and easily cultured. First, MOLM-14 cells were washed twice with 50 mL DPBS and resuspended in 2 mL DPBS. To prepare a stock solution of 0.5M MOLM-14 cells per 1 mL DPBS, cell viability and concentration were determined and counted with Trypan blue staining using a cell counter (Countess II Automated Cell Counters, Invitrogen). Next, a stock solution of 1 mg / mL click component (TCO-NHS ester, TCO-PEG3-NHS ester, TCO-PEG3-maleimide, Tz- NHS ester or BCN-NHS ester) was made with dimethyl sulfoxide (DMSO) (Sigma-Aldrich). Then, 1 mL of the cell stock solution was taken added to a 15 mL Falcon tube, where the cells were functionalised with click component (0.2, 0.1, 0.05, 0.025, 0.0125, 0.00625, 0.003125, or 0 g / L), after which the cells were incubated for 30-45 minutes at 4 ℃. After that, cells were diluted to a concentration of 20000 cells per 250 µL in complete RPMI medium, and seeded into one 96-well plate per time point (Sigma-Aldrich). At each time point, 5 µL of 0.2 µg / µL complementary fluorescent (Tz-CF647, TCO-CF647 or azide- CF647) or radioactive (Al[18F]F-Tz-PEG7-NODA) click component in DPBS was added in darkness. The plates were incubated at room temperature for 15 minutes. Binding of the fluorescent click components to the cells was analysed using flow cytometry (Guava 12HT®, 640-nm laser, Merck Millipore). Binding of the radioactive click components was analysed using a gamma counter (Wallac Wizard 1480, Perkin Elmer). Example 2 Cells can be functionalised with click up until a maximum concentration Cells can be functionalised with click components without affecting cell viability up until a maximum concentration. For the MOLM-14 cells tested here, the maximum click component concentration that could be used without affecting cell viability was at least 0.094 mM for TCO-NHS ester, TCO-PEG9-maleimide and TCO-PEG3-maleimide, but less than 0.023 mM for TCO-PEG3-NHS ester, BCN-NHS ester and Tz-NHS ester (Figure 8). The click component remains available at the cell surface for multiple days. Click components at the cell surface remain available for the click reaction for multiple days (Figure 9). This is a crucial finding, because it was previously unknown and impossible to predict if the click component would be internalised and / or degraded and, as such, would no longer be available for binding. Interestingly, including a linker between click component (TCO) and maleimide increases the sustained availability of the click component at the cell surface. As such, including a linker will enable the tracking / detection of cells for longer periods, compared to when a linker is absent. Here, the remaining fraction of TCO-PEG3, TCO-PEG9 and TCO at the cell surface was measured by gamma counting using radiolabelled Tz. Materials and Methods Human leukaemia MOLM-14 cells were used, which are commercially available and easily cultured. First, MOLM-14 cells were washed twice with 50 mL DPBS and resuspended in 2 mL DPBS. To prepare a stock solution of 0.5M MOLM-14 cells per 1 mL DPBS, cell viability and concentration were determined and counted with Trypan blue staining using a cell counter (Countess II Automated Cell Counters, Invitrogen). Next, a stock solution of 1 mg / mL click component (TCO-NHS ester, TCO-PEG9-maleimide, TCO-PEG3-maleimide, TCO-PEG3-NHS ester, BCN-NHS ester or Tz-NHS ester) was made with dimethyl sulfoxide (DMSO) (Sigma-Aldrich). Then, the cell stock solution was added to a 15 mL Falcon tube, where the cells were functionalised with click component (0.094, 0.047, 0.023, 0 mM), after which the cells were incubated for 30-45 minutes at 4 ℃. After that, cells were diluted to a concentration of 20000 cells per 250 µL in complete RPMI medium, and seeded into one 96-well plate per time point (Sigma-Aldrich). At each time point, radioactive (Al[18F]F- Tz-PEG7-NODA) click component in DPBS was added. The plates were incubated at room temperature for 15 minutes. Binding of the radioactive click components was analysed using a gamma counter (Wallac Wizard 1480, Perkin Elmer). Cell viability after 3 days was determined with Trypan blue staining using a cell counter. Example 3 Conjugates of cells containing a first click component can be detected in vivo by a second click component containing a detectable moiety hMSCs functionalised with TCO-PEG3-maleimide on the cell surface were injected in heart muscle and left kidney of swine. After 4 hours, the injected cells could well be detected by PET imaging using an18F-labelled 1,2,4,5-tetrazine. As a control, hMSCs without click component were injected in the right kidney. These experiments provide in vivo proof-of- concept of the described method. Materials and Methods Human mesenchymal stem cells (hMSCs) were functionalised with 75 µM TCO-PEG3- maleimide, after which 3 million cells were transplanted in a swine heart around the apex region of the left ventricle as well as in left kidney, using our unique endovascular Extroducer™^ for trans-vessel wall delivery. As a control, non-functionalised hMSCs were transplanted in the right kidney. After transplantation,18F-labelled Tz (~5 MBq) was intravenously injected for the bioorthogonal click reaction with the functionalised hMSCs. PET imaging was performed after 4 hours. References Weber, E. W.; Maus, M. V.; Mackall, C. L., The Emerging Landscape of Immune Cell Therapies. Cell 2020, 181 (1), 46-62. Hoang, D. M.; Pham, P. T.; Bach, T. Q.; Ngo, A. T. L.; Nguyen, Q. T.; Phan, T. T. K.; Nguyen, G. H.; Le, P. T. T.; Hoang, V. T.; Forsyth, N. R.; Heke, M.; Nguyen, L. T., Stem cell-based therapy for human diseases. Signal Transduction and Targeted Therapy 2022, 7 (1), 272. Oliveira, B. L.; Guo, Z.; Bernardes, G. J. L., Inverse electron demand Diels–Alder reactions in chemical biology. Chem. Soc. Rev. 2017, 46 (16), 4895-4950. Handula, M.; Chen, K.-T.; Seimbille, Y. IEDDA: An Attractive Bioorthogonal Reaction for Biomedical Applications Molecules [Online], 2021. Friberger, I.; Jussing, E.; Han, J.; Goos, J. A. C. M.; Siikanen, J.; Kaipe, H.; Lambert, M.; Harris, R. A.; Samén, E.; Carlsten, M.; Holmin, S.; Tran, T. A., Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications. Mol. Imaging Biol. 2021, 23 (6), 952-962. Lapi, S.; McConathy, J.; Jeffers, C.; Bartels, J.; Houson, H.; White, S.; Younger, J., <strong>First-in-Human Imaging of 89Zr-oxine Labelled Autologous Leukocytes in Healthy Volunteers< / strong>. J. Nucl. Med. 2022, 63 (supplement 2), 2447. Perrin, J.; Capitao, M.; Mougin-Degraef, M.; Guérard, F.; Faivre-Chauvet, A.; Rbah- Vidal, L.; Gaschet, J.; Guilloux, Y.; Kraeber-Bodéré, F.; Chérel, M.; Barbet, J., Cell Tracking in Cancer Immunotherapy. Frontiers in Medicine 2020, 7. Altai, M.; Membreno, R.; Cook, B.; Tolmachev, V.; Zeglis, B. M., Pretargeted Imaging and Therapy. J. Nucl. Med. 2017, 58 (10), 1553-1559. Simão, D. C.; Zarrabi, K. K.; Mendes, J. L.; Luz, R.; Garcia, J. A.; Kelly, W. K.; Barata, P. C. Bispecific T-Cell Engagers Therapies in Solid Tumors: Focusing on Prostate Cancer Cancers (Basel) [Online], 2023. Martino, M.; Alati, C.; Canale, F. A.; Musuraca, G.; Martinelli, G.; Cerchione, C. A Review of Clinical Outcomes of CAR T-Cell Therapies for B-Acute Lymphoblastic Leukemia Int. J. Mol. Sci. [Online], 2021. Irvine, D. J.; Maus, M. V.; Mooney, D. J.; Wong, W. W., The future of engineered immune cell therapies. Science 2022, 378 (6622), 853-858. Sterner, R. C.; Sterner, R. M., CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021, 11 (4), 69. Blackman et al., "The Tetrazine Ligation: Fast Bioconjugation based on Inverse-electron- demand Diels-Alder Reactivity." J. Am. Chem. Soc. 2008; 130, 13518-13519 Spicer et al, "Selective chemical protein modification." Nature Communications. 2014; 5:4740 Tyle P. “lontophoretic Devices for Drug Delivery”. Pharm Res. 1986 Dec;3(6):318-26. doi: 10.1023 / A:1016327822325. PMID: 24271830.

Claims

Claims 1. Use of an isolated conjugate for detecting the presence and / or location of a cell or vesicle in a subject, wherein the isolated conjugate comprises the cell or vesicle and a first click component, wherein the first click component is covalently conjugated to the cell or vesicle surface via a thiol conjugate; the first click component is selected from a dienophile (DP) or a diene; and the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4- triazine, optionally wherein the covalent conjugation is carried out ex vivo.

2. A use according to Claim 1, wherein the first click component is covalently conjugated to the cell or vesicle surface via a conjugate of maleimide, vinylsulfone, haloacetyl, pyridyldisulfide or thiosulfonate.

3. A use according to any one of the preceding claims, wherein the first click component is covalently conjugated to the cell or vesicle surface via a thiol-maleimide conjugate.

4. A use according to any one of the preceding claims, wherein the first click component comprises a linker.

5. A use according to Claim 4, wherein the linker comprises or consists of at least one PEG group, such as –(PEG)3- or –(PEG)9-.

6. A use according to any one of the preceding claims, wherein the dienophile is a strained dienophile.

7. A use according to any one of the preceding claims, wherein the dienophile comprises a non-aromatic eight-membered ring, such as a cyclooctene ring (CO).

8. A use according to any one of the preceding claims, wherein the dienophile is a trans-cyclooctene (TCO) or bicyclononyne.

9. A use according to any of the preceding claims, wherein the cell is a therapeutic cell and / or the vesicle is a therapeutic vesicle.

10. A use according to any of the preceding claims, wherein the cell is a stem cell or progenitor cell (such as Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs), Hematopoietic Stem Cells (HSCs)), Mesenchymal Stem Cells (MSCs) or Neural Stem Cells) or an immune cell (such as macrophages, lymphocytes, T-cells (including Chimeric Antigen Receptor T Cells (CAR-T Cells), Natural-Killer (NK) cells, NK-like T-cells or Tumor infiltrating lymphocytes (TILs), bone marrow cells, and Dendritic Cells).

11. A use according to any of the preceding claims, wherein the first click component is not covalently conjugated to the cell or vesicle surface by metabolic labelling.

12. A use according to any one of the preceding claims, wherein the isolated conjugate further comprises a second click component, which is covalently bound to the first click component.

13. A use according to Claim 12, wherein the second click component comprises a detectable moiety.

14. A use according to Claim 12 or 13, wherein i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile.

15. A pharmaceutical composition for use in detecting the presence and / or location of a cell or vesicle in a subject, wherein the pharmaceutical composition comprises an isolated conjugate as defined in any of Claims 1-14, together with a diluent, excipient or carrier, wherein the pharmaceutical composition is in a form suitable for administration to a subject.

16. An isolated conjugate as defined in any of Claims 1-14 for use in detecting the presence and / or location of a cell or vesicle in a subject.

17. Use of an isolated conjugate as defined in any of Claims 1-14, or a pharmaceutical composition as defined in Claim 15, in the manufacture of a medicament for detecting the presence and / or location of a cell or vesicle in a subject.

18. A method of detecting the presence and / or location of a cell or vesicle in a subject, the method comprising administering an isolated conjugate as defined in any of Claims 1- 14, or a pharmaceutical composition as defined in Claim 15, to the subject.

19. The use according to any one of Claims 1 to 14, the pharmaceutical composition for use according to Claim 15, the isolated conjugate for use according to Claim 16, the use according to Claim 17, or the method according to Claim 18, wherein before administration to the subject, the isolated conjugate is contacted ex vivo with a second click component, and wherein the second click component binds covalently to the first click component ex vivo so as to make the conjugate comprising a cell or vesicle and a first click component detectable.

20. The use according to any one of Claims 1 to 14, the pharmaceutical composition for use according to Claim 15, the isolated conjugate for use according to Claim 16, the use according to Claim 17, or the method according to Claim 18, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to make the conjugate comprising a cell or vesicle and a first click component detectable.

21. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to Claim 20, wherein the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component.

22. The use, the isolated conjugate for use, the pharmaceutical composition for use, the use, or the method according to Claim 20, wherein the second click component is administered to the subject after the isolated conjugate comprising a cell or vesicle and a first click component.

23. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to any of Claims 19-22, wherein the conjugate comprising a cell orvesicle and a first click component is made detectable in the subject for at least 1 day, such as 3 days, 5 days, 7 days, or 14 days.

24. The use, the isolated conjugate for use, the pharmaceutical composition for use, the use, or the method according to any of Claims 19-23, wherein the second click component comprises a detectable moiety.

25. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to any one of Claims 20-24, wherein detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject is carried out after the clearance of excess isolated conjugate comprising a cell and a first click component and / or excess second click component.

26. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to any one of Claims 20-25, wherein the subject is administered a clearing agent.

27. Use of an isolated conjugate for directing a cell or vesicle to a target site in a subject, wherein the isolated conjugate comprises the cell or vesicle and a first click component, wherein the first click component is covalently conjugated to the cell or vesicle surface via a thiol conjugate; the first click component is selected from a dienophile (DP) or a diene; and the dienophile is an alkene or an alkyne and the diene is a 1,2,4,5-tetrazine or 1,2,4- triazine, optionally wherein the covalent conjugation is carried out ex vivo.

28. The use according to Claim 27, wherein the isolated conjugate is as defined in any one of Claims 2-14.

29. An isolated conjugate as defined in any one of Claims 27 and 28, for use in directing a cell or vesicle to a target site in a subject.

30. A pharmaceutical composition for use in directing a cell or vesicle to a target site in a subject, wherein the pharmaceutical composition comprises an isolated conjugate asdefined in any of one of Claims 27 and 28, together with a diluent, excipient or carrier, wherein the pharmaceutical composition is in a form suitable for administration to a subject.

31. Use of an isolated conjugate as defined in any of Claims 27 and 28, or a pharmaceutical composition as defined in Claim 30, in the manufacture of a medicament for directing a cell or vesicle to a target site in a subject.

32. A method of directing a cell or vesicle to a target site in a subject, the method comprising administering an isolated conjugate as defined in any of Claims 27 and 28, or a pharmaceutical composition as defined in Claim 30, to the subject.

33. The use according to any one of Claims 27 and 28, the isolated conjugate for use according to Claim 29, the pharmaceutical composition for use according to Claim 30, the use according to Claim 31, or the method according to Claim 32, wherein the subject is also administered a second click component, and wherein the second click component binds covalently to the first click component in the subject so as to direct the conjugate comprising a cell or vesicle and a first click component to the target site in the subject.

34. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to Claim 33, wherein the second click component is administered to the subject before the isolated conjugate comprising a cell or vesicle and a first click component.

35. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to Claim 34, wherein the second click component is covalently attached to a targeting molecule.

36. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to Claim 35, wherein the targeting molecule is selected from the group comprising antibodies or antigen binding fragments thereof, proteins, aptamers, oligopeptides, oligonucleotides, oligosaccharides, as well as peptides, peptoids and organic drug compounds.

37. The use according to any one of Claims 27, 28 and 33-36, the isolated conjugate for use according to any one of Claims 29 and 33-36, the pharmaceutical composition for use according to any one of Claims 30 and 33-36, the use according to any one of Claims 31 and 33-36, or the method according to any of Claims 32 to 36, further comprising detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject.

38. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to Claim 37, wherein detecting the presence and / or location of the conjugate comprising a cell or vesicle and a first click component in the subject is carried out after the clearance of excess second click component.

39. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to Claim 37 or 38, wherein the subject is administered a clearing agent.

40. The use, the isolated conjugate for use, the pharmaceutical composition for use, or the method according to any one of Claims 33-39, wherein: i. the first click component is a dienophile and the second click component is a diene; or ii. the first click component is a diene and the second click component is a dienophile.

41. A kit comprising: a. an isolated conjugate as defined in any of Claims 1-14; b. a second click component selected from a dienophile (DP) or a diene, optionally wherein the second click component comprises a detectable moiety; and c. instructions for practicing a use as defined in any of Claims 1-14, 17 and 19- 28, 31, and 33-40, or a method as defined in any of Claims 18-26 and 32- 40.

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