Therapies for preventing or treating inflammatory eye disease

Abstract

The present invention provides a combination comprising (a) a TNF inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same, as a combined preparation for simultaneous, separate or sequential use in preventing or treating an inflammatory eye disease. The present invention also provides a vector comprising a nucleotide sequence encoding a CD3 inhibitor, wherein the nucleotide sequence encoding the CD3 inhibitor is operably linked to an inflammation-inducible promoter.

Description

[0001]THERAPIES FOR PREVENTING OR TREATING INFLAMMATORY EYE DISEASE FIELD OF THE INVENTIONThe present invention relates to a combination therapy for preventing or treating aninflammatory eye disease. The present invention also relates to CD3 inhibitors,polynucleotides, cells, vectors, kits, products, and pharmaceutical compositions for preventingor treating an inflammatory eye disease. BACKGROUND TO THE INVENTION Chronic inflammation in the eye can lead to cumulative damage that eventually causes significant vision loss. Chronic non-infectious uveitis is a sight-threatening intraocular inflammation that accounts for 10% of blindness in the working-age population and has a disproportionately large economic burden (see e.g. Joltikov, K.A. and Lobo-Chan, A.M., 2021. Frontiers in Medicine, 8:695904). Uveitis may include intraocular inflammation that affects the uvea and adjacent structures, such as the cornea, vitreous humor, retina, and optic nerve. Most commonly, uveitis is idiopathic, but can be linked to infection, malignancy, or underlying inflammatory conditions such as spondyloarthritis, sarcoidosis, juvenile idiopathic arthritis (JIA), inflammatory bowel disease, rheumatoid arthritis, tubulointerstitial nephritis, and other autoinflammatory diseases (see e.g. Rosenbaum, J.T., et al., 2019. Seminars in Arthritis and Rheumatism, 49(3), pp.438-445). Currently, the first line treatment for non-infectious uveitis is corticosteroids, which can be administered topically, periocularly, intraocularly, or systemically. However, there are issues associated with this treatment option. Systemic administration of corticosteroids has a number of well-known side effects that can lead to adverse events, and while local administration of corticosteroids can reduce the concentrations required, there is a need for repeat injections as the ocular concentration of the drug declines over time. Due to the recurrent nature of the condition, patients may need to be maintained on continual systemic corticosteroids treatment, which can lead to numerous adverse effects (see e.g. Valenzuela, R.A., et al., 2020. Frontiers in Pharmacology, 11:655). Local treatment options, including intraocular steroid-based implants and intravitreal injection, have not significantly improved the clinical landscape. Whilst effective at reducing recurrence in milder disease, these are associated with significant adverse events, such as cataracts and glaucoma. Immunosuppressant therapy (IMT) is an alternative to corticosteroid therapy, including antimetabolites, calcineurinic inhibitors, and alkylating agents. When conventionalcorticosteroids and IMT fail, biological agents and biologics such as TNF inhibitors, IL-1blockers, and anti-CD20 may be used.However, these agents are associated with adverse events. For example, adverse effectsassociated with TNF inhibitors include development of autoimmune diseases, increased riskof infection, reactions at the injection site, increased risk of malignancy and worsening ofdemyelinating disorders (see e.g. Valenzuela, R.A., et al., 2020. Frontiers in Pharmacology,11:655). Moreover, there remains up to 40% incidence of recurrent flares despite repeated,systemic dosing of TNF inhibitors. Thus, there is an unmet need for consistent control ofdisease in patients. Thus, there is a demand for new approaches for treating or preventing inflammatory eye diseases, such as uveitis. SUMMARY OF THE INVENTIONThe present inventors have developed therapies for treating or preventing inflammatory eyediseases, such as uveitis, in which TNF inhibitors and CD3 inhibitors are delivered to the eye.The inventors have surprisingly demonstrated that a combination therapy comprisingintraocular administration of a TNF inhibitor and a CD3 inhibitor (for example eachadministered in the form of a vector encoding the same) may have increased efficacycompared to a TNF inhibitor monotherapy. The combination therapy may therefore representan improved approach to prevent or treat inflammatory eye disease compared to themonotherapy. Dual targeting of cytokine and cellular mediators of inflammation may increaseefficacy and response rate.The inventors have also surprisingly demonstrated that vectors encoding a transgene underthe control of an inflammation-inducible promoter may allow for inflammation-inducible expression of the transgene in the eye. When expression of a TNF inhibitor and / or a CD3 inhibitor is coupled to an inflammation-inducible promoter, the combination therapy may therefore provide an adaptable and responsive dose level to prevent or treat inflammatory eye disease. Such a combination therapy may prevent re-occurrence of inflammation and / or maintain inflammation at a sub-clinical level, thereby preventing cumulative damage, whilstreducing the occurrence of adverse events imparted by long term systemicimmunosuppression.In one aspect, the present invention provides a combination of (a) a TNF inhibitor, or apolynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor,or a polynucleotide comprising a nucleotide sequence encoding the same. The combination of the present invention may be provided in any suitable form. For example,in the form of a bicistronic or multicistronic vector, two separate vectors, or a product, kit orpharmaceutical composition comprising the combination.In one aspect, the present invention provides a vector comprising: (a) a nucleotide sequenceencoding a TNF inhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor. Suitably, the nucleotide sequence encoding a TNF inhibitor is linked to the nucleotide sequence encoding a CD3 inhibitor by a nucleotide sequence encoding a 2A self-cleaving peptide, an enzymatically cleavable peptide motif, and / or an IRES element. In some embodiments, the nucleotide sequence encoding a TNF inhibitor is linked to the nucleotide sequence encoding a CD3 inhibitor by a nucleotide sequence encoding a 2A self-cleaving peptide. In some embodiments, the nucleotide sequence encoding a TNF inhibitor and the nucleotide sequence encoding a CD3 inhibitor are each operably linked to the same promoter. In some embodiments, the vector comprises a nucleotide sequence comprising or consisting of from 5’ to 3’: a promoter; the nucleotide sequence encoding a TNF inhibitor; a 2A self- cleaving peptide, an enzymatically cleavable peptide motif, and / or an IRES element; and the nucleotide sequence encoding a CD3 inhibitor. In some embodiments, the vector comprises a nucleotide sequence comprising or consisting of from 5’ to 3’: a promoter; the nucleotide sequence encoding a CD3 inhibitor; a 2A self-cleaving peptide, an enzymatically cleavable peptide motif, and / or an IRES element; and the nucleotide sequence encoding a TNF inhibitor.In another aspect, the present invention provides a kit comprising: (a) a vector comprising anucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a pharmaceutical composition comprising:(a) a vector comprising a nucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a product comprising: (a) a vector comprisinga nucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor, as a combined preparation for simultaneous, separate or sequential use in therapy.In another aspect, the present invention provides a kit comprising: (a) a TNF inhibitor, or apolynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same.In another aspect, the present invention provides a pharmaceutical composition comprising:(a) a TNF inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same.In another aspect, the present invention provides a product comprising: (a) a TNF inhibitor, ora polynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same, as acombined preparation for simultaneous, separate or sequential use in therapy.In preferred embodiments, the TNF inhibitor is an anti-TNF antibody or a fragment thereof.Any suitable anti-TNF antibody or fragment thereof may be used. In some embodiments, theTNF inhibitor is any of adalimumab or a fragment thereof, infliximab or a fragment thereof,golimumab or a fragment thereof, or certolizumab or a fragment thereof. In someembodiments, the TNF inhibitor is adalimumab or a fragment thereof, or infliximab or afragment thereof. In some embodiments, the TNF inhibitor is an anti-TNF antibody fragment.Any suitable anti-TNF antibody fragment may be used. In some embodiments, the anti-TNF antibody fragment is an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a single chain antibody (scFv), or a single-domain antibody (sdAb). In some embodiments, the anti-TNF antibody fragment is an antigen-binding fragment (Fab). In some embodiments, the TNF inhibitor is adalimumab or a fragment thereof. In some embodiments, the TNF inhibitor is an antigen binding fragment (Fab) of adalimumab. In some embodiments, the TNF inhibitor is an anti-TNF antibody or a fragment thereof comprising oneor more CDR regions selected from SEQ ID NOs: 16 to 21 or derivatives thereof comprisingone amino acid substitution. In some embodiments, the TNF inhibitor is an anti-TNF antibody or a fragment thereof comprising CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2,LCDR3 comprising or consisting of SEQ ID NOs: 16, 17, 18, 19, 20 and 21 respectively, orderivatives thereof comprising one amino acid substitution. In some embodiments, the TNF inhibitor is an anti-TNF antibody or a fragment thereof comprising a heavy chain comprisingor consisting of a sequence with at least 70% identity to SEQ ID NO: 22 and / or a light chaincomprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 23. In some embodiments, the heavy chain is encoded by a nucleotide sequence having at least 70%identity to SEQ ID NO: 62 and / or the light chain is encoded by a nucleotide sequence havingat least 70% identity to SEQ ID NO: 63. The nucleotide sequence encoding the heavy chain and the nucleotide sequence encoding the light chain may be connected via a linker sequence. Suitably, the linker sequence encodes a 2A self-cleaving peptide, and / or an enzymatically cleavable peptide motif. In some embodiments, the linker sequence encodes a 2A self- cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9. The nucleotide sequence encoding the heavy chain and / or the nucleotide sequence encoding the light chain may each be operably linked to a signal sequence. In some embodiments, the signal sequence encodes a signal peptide selected from any of: a Human Growth Hormone (HGH) signal peptide, an interleukin-2 (IL-2) signal peptide, a CD5 signal peptide, an immunoglobulin Kappa light chain signal peptide, a trypsinogen signal peptide, a serumalbumin signal peptide, and a prolactin signal peptide. In some embodiments, the nucleotidesequence encoding a TNF inhibitor encodes an anti-TNF antibody or a fragment comprising or consisting of a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 22, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 23. In some embodiments, the nucleotide sequence encoding a TNF inhibitor encodes an anti-TNF antibody or a fragment comprising or consistingof an amino acid sequence having at least 70% identity to SEQ ID NO: 66. In someembodiments, the nucleotide sequence encoding a TNF inhibitor comprises or consists of: a nucleotide sequence having at least 70% identity to SEQ ID NO: 62, a nucleotide sequencehaving at least 70% sequence identity to SEQ ID NO: 10 or 11, and a nucleotide sequencehaving at least 70% identity to SEQ ID NO: 63. In some embodiments, the nucleotide sequence encoding a TNF inhibitor comprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO: 67.In preferred embodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereof.Any suitable anti-CD3 antibody or fragment thereof may be used. In some embodiments, theCD3 inhibitor is any of foralumab or a fragment thereof, teplizumab or a fragment thereof,visilizumab or a fragment thereof, otelixizumab or a fragment thereof, muromonab-CD3 or afragment thereof, T3 / 4.A or a fragment thereof, YTH12.5 or a fragment thereof, or HuM291 ora fragment thereof. In some embodiments, the CD3 inhibitor is foralumab or a fragmentthereof, teplizumab or a fragment thereof, visilizumab or a fragment thereof, or otelixizumabor a fragment thereof.In some embodiments, the CD3 inhibitor is an anti-CD3 antibody fragment. Any suitable anti-CD3 antibody fragment may be used. In some embodiments, the anti-CD3 antibody fragmentis an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a single chain antibody(scFv), or a single-domain antibody (sdAb). In some embodiments, the anti-CD3 antibodyfragment is an antigen-binding fragment (Fab). In some embodiments, the CD3 inhibitor is anantigen binding fragment (Fab) of foralumab, teplizumab, visilizumab, or otelixizumab.In some embodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereofcomprising one or more CDR regions selected from: (a) SEQ ID NOs: 70 to 75 or derivativesthereof comprising one amino acid substitution; (b) SEQ ID NOs: 81 to 86 or derivativesthereof comprising one amino acid substitution; (c) SEQ ID NOs: 92 to 97 or derivativesthereof comprising one amino acid substitution; or (d) SEQ ID NOs: 103 to 108 or derivativesthereof comprising one amino acid substitution. In some embodiments, the CD3 inhibitor is ananti-CD3 antibody or a fragment thereof comprising: (a) CDR regions HCDR1, HCDR2,HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs: 70, 71, 72, 73, 74and 75 respectively, or derivatives thereof comprising one amino acid substitution; (b) CDRregions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQID NOs: 81, 82, 83, 84, 85 and 86 respectively, or derivatives thereof comprising one aminoacid substitution; (c) CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3comprising or consisting of SEQ ID NOs: 92, 93, 94, 95, 96 and 97 respectively, or derivativesthereof comprising one amino acid substitution; or (d) CDR regions HCDR1, HCDR2, HCDR3,LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs: 103, 104, 105, 106, 107and 108 respectively, or derivatives thereof comprising one amino acid substitution. In someembodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereof comprising: (a)a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ IDNO: 76 and / or a light chain comprising or consisting of a sequence with at least 70% identityto SEQ ID NO: 77; (b) a heavy chain comprising or consisting of a sequence with at least 70%identity to SEQ ID NO: 87 and / or a light chain comprising or consisting of a sequence with atleast 70% identity to SEQ ID NO: 88; (c) a heavy chain comprising or consisting of a sequencewith at least 70% identity to SEQ ID NO: 98 and / or a light chain comprising or consisting of asequence with at least 70% identity to SEQ ID NO: 99; or (d) a heavy chain comprising orconsisting of a sequence with at least 70% identity to SEQ ID NO: 109 and / or a light chaincomprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 110. In someembodiments: (a) the heavy chain is encoded by a nucleotide sequence having at least 70%identity to SEQ ID NO: 125 and / or the light chain is encoded by a nucleotide sequence havingat least 70% identity to SEQ ID NO: 126; (b) the heavy chain is encoded by a nucleotidesequence having at least 70% identity to SEQ ID NO: 127 and / or the light chain is encodedby a nucleotide sequence having at least 70% identity to SEQ ID NO: 128; (c) the heavy chainis encoded by a nucleotide sequence having at least 70% identity to SEQ ID NO: 129 and / orthe light chain is encoded by a nucleotide sequence having at least 70% identity to SEQ IDNO: 130; or (d) the heavy chain is encoded by a nucleotide sequence having at least 70%identity to SEQ ID NO: 131 and / or the light chain is encoded by a nucleotide sequence havingat least 70% identity to SEQ ID NO: 132. The nucleotide sequence encoding the heavy chainand the nucleotide sequence encoding the light chain may be connected via a linker sequence. Suitably, the linker sequence encodes a 2A self-cleaving peptide, and / or an enzymatically cleavable peptide motif. In some embodiments, the linker sequence encodes a 2A self- cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9. The nucleotide sequence encoding the heavy chain and / or the nucleotide sequence encoding thelight chain may each be operably linked to a signal sequence. In some embodiments, thesignal sequence encodes a signal peptide selected from any of: a Human Growth Hormone (HGH) signal peptide, an interleukin-2 (IL-2) signal peptide, a CD5 signal peptide, an immunoglobulin Kappa light chain signal peptide, a trypsinogen signal peptide, a serumalbumin signal peptide, and a prolactin signal peptide. In some embodiments, the nucleotidesequence encoding a CD3 inhibitor encodes an anti-CD3 antibody or a fragment comprising or consisting of: (a) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 76, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 77; (b) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 87, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 88; (c) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 98, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 99; or (d) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 109, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequencewith at least 70% identity to SEQ ID NO: 110. In some embodiments, the nucleotide sequenceencoding a CD3 inhibitor encodes an anti-CD3 antibody or a fragment comprising or consistingof: (a) an amino acid sequence having at least 70% identity to SEQ ID NO: 133; (b) an amino acid sequence having at least 70% identity to SEQ ID NO: 135; (c) an amino acid sequence having at least 70% identity to SEQ ID NO: 137; or (d) an amino acid sequence having at least70% identity to SEQ ID NO: 139. In some embodiments, the nucleotide sequence encoding aCD3 inhibitor comprises or consists of: (a) a nucleotide sequence having at least 70% identityto SEQ ID NO: 125, a nucleotide sequence having at least 70% sequence identity to SEQ IDNO: 10 or 11, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 126; (b)a nucleotide sequence having at least 70% identity to SEQ ID NO: 127, a nucleotide sequencehaving at least 70% sequence identity to SEQ ID NO: 10 or 11, and a nucleotide sequencehaving at least 70% identity to SEQ ID NO: 128; (c) a nucleotide sequence having at least70% identity to SEQ ID NO: 129, a nucleotide sequence having at least 70% sequence identityto SEQ ID NO: 10 or 11, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 130; (d) a nucleotide sequence having at least 70% identity to SEQ ID NO: 131, anucleotide sequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, and anucleotide sequence having at least 70% identity to SEQ ID NO: 132. In some embodiments,the nucleotide sequence encoding a CD3 inhibitor comprises or consists of: (a) a nucleotidesequence having at least 70% identity to SEQ ID NO: 134; (b) a nucleotide sequence havingat least 70% identity to SEQ ID NO: 136; (c) a nucleotide sequence having at least 70% identityto SEQ ID NO: 138; or (d) a nucleotide sequence having at least 70% identity to SEQ ID NO:140. In preferred embodiments, the nucleotide sequence encoding a TNF inhibitor is operablylinked to an inflammation-inducible promoter and / or the nucleotide sequence encoding a CD3inhibitor is operably linked to an inflammation-inducible promoter. In some embodiments, the nucleotide sequence encoding a TNF inhibitor is operably linked to an inflammation-induciblepromoter and the nucleotide sequence encoding a CD3 inhibitor is operably linked to aninflammation-inducible promoter. In some embodiments, the nucleotide sequence encoding aTNF inhibitor and the nucleotide sequence encoding a CD3 inhibitor are operably linked to thesame inflammation-inducible promoter. Any suitable inflammation-inducible promoter may beused. Suitably, the inflammation-inducible promoter comprises one or more inflammation-inducible transcription factor binding motif selected from: an AP-1 transcription factor binding motif; a NF-κB transcription factor binding motif; an IRF transcription factor binding motif; a STAT transcription factor binding motif; and a NFAT transcription factor binding motif or anycombination thereof. In some embodiments, the inflammation-inducible promoter comprisesone or more AP-1 binding motif and / or one or more NF-κB binding motif. In someembodiments, the inflammation-inducible promoter comprises two or more AP-1 bindingmotifs and / or two or more NF-κB binding motifs, three or more AP-1 binding motifs and / or three or more NF-κB binding motifs, four or more AP-1 binding motifs and / or four or more NF- κB binding motifs, or five or more AP-1 binding motifs and / or five or more NF-κB binding motifs. In some embodiments, the inflammation-inducible promoter comprises at least one AP-1binding motif coupled to at least one NF-κB binding motif. In some embodiments, theinflammation-inducible promoter comprises five AP-1 binding motifs coupled to five NF-κBbinding motifs. Suitably, an AP-1 binding motif comprises or consists of SEQ ID NO: 151, orcomprises or consists of any of SEQ ID NOs: 152-154 or derivatives thereof comprising onenucleotide substitution. Suitably, a NF-κB binding motif comprises or consists of SEQ ID NO:155, or comprises or consists of SEQ ID NO: 156 or a derivative thereof comprising two orfewer nucleotide substitutions. In some embodiments, the inflammation-inducible promotercomprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO: The vector(s) may comprise any other suitable vector elements. The vector(s) may comprise a polyadenylation sequence. Suitably, the polyadenylation sequence is selected from any of: a bovine growth hormone (bGH) polyadenylation sequence, a SV40 polyadenylationsequence, and a rabbit beta-globin polyadenylation sequence. In some embodiments, thepolyadenylation sequence comprises or consists of a nucleotide sequence having at least70% identity to SEQ ID NO: 163. The vector(s) may comprise a woodchuck hepatitis post-transcriptional regulatory element (WPRE). In some embodiments, the WPRE comprises orconsists of a nucleotide sequence having at least 70% identity to SEQ ID NO: 164. Thevector(s) may comprise an intron. Suitably, the intron is selected from a beta-globin intron ora SV40 intron. In some embodiments, the intron comprises or consists of a nucleotidesequence having at least 70% identity to SEQ ID NO: 165. In preferred embodiments, the vector is a viral vector. Any suitable viral vector may be used. Suitably, the viral vector is any of a parvoviral vector, preferably an adeno-associated virus (AAV) vector, an adenoviral vector, a herpes simplex viral vector, an anelloviral vector, aretroviral vector or a lentiviral vector. In preferred embodiments, the vector is an adeno-associated virus (AAV) vector. In preferred embodiments, the vector is an AAV vector particle.The AAV vector particle may be pseudotyped to confer ocular tissue tropism. Suitably, theAAV vector particle comprises AAV2 capsid proteins or AAV2 capsid variant proteins, optionally wherein the AAV2 capsid variant is selected from any of: AAV2.tYF, AAV2.7m8,R100, AAV2.GL and AAV2.NN. The vector may comprise one or more inverted terminalrepeats (ITRs).In another aspect, the present invention provides a cell comprising (i) the vector of the presentinvention; and / or (ii) (a) a vector comprising a nucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor. The cell may be an isolated cell.In another aspect, the present invention provides a kit for the production of (i) the vector of thepresent invention; and / or (ii) (a) a vector comprising a nucleotide sequence encoding a TNFinhibitor, and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a pharmaceutical composition comprising (i)the vector of the present invention; (ii) (a) a vector comprising a nucleotide sequence encodinga TNF inhibitor, and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor;or (iii) the cell of the present invention. The vector(s) or cell may be in combination with apharmaceutically acceptable carrier, diluent or excipient. In another aspect, the present invention provides a vector according to the present invention,a cell according to the present invention, and / or a pharmaceutical composition according tothe present invention, for use as a medicament. In another aspect, the present invention provides use of a vector according to the presentinvention, a cell according to the present invention, or a pharmaceutical composition accordingto the present invention, for the manufacture of a medicament. In another aspect, the present invention provides a method comprising administering a vectoraccording to the present invention, a cell according to the present invention, or apharmaceutical composition according to the present invention, to a subject in need thereof.In another aspect, the present invention provides a vector for use in preventing or treating aninflammatory eye disease, wherein the vector comprises: (a) a nucleotide sequence encoding a TNF inhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides use of a vector in the manufacture of amedicament for preventing or treating an inflammatory eye disease, wherein the vector comprises: (a) a nucleotide sequence encoding a TNF inhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a method for preventing or treating aninflammatory eye disease, wherein the method comprises administering a vector to a subjectin need thereof, wherein the vector comprises: (a) a nucleotide sequence encoding a TNFinhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a vector according to the present invention,a cell according to the present invention, and / or a pharmaceutical composition according tothe present invention, for use in preventing or treating an inflammatory eye disease. In another aspect, the present invention provides use of a vector according to the presentinvention, a cell according to the present invention, or a pharmaceutical composition accordingto the present invention, for the manufacture of a medicament for preventing or treating aninflammatory eye disease. In another aspect, the present invention provides a method of preventing or treating an inflammatory eye disease comprising administering a vector according to the presentinvention, a cell according to the present invention, or a pharmaceutical composition accordingto the present invention, to a subject in need thereof.The inflammatory eye disease may be any inflammatory eye disease. Suitably, theinflammatory eye disease is uveitis. The vector(s) or pharmaceutical composition may beadministered in response to relapse of an inflammatory eye disease, particularly wherein theinflammatory eye disease is uveitis.The vector(s) or pharmaceutical composition may be administered by any suitable route.Suitably, the vector(s) or pharmaceutical composition are administered intraocularly. In someembodiments, the vector(s) or pharmaceutical composition are administered via intravitreal,subretinal, subconjunctival, sub-Tenon’s or suprachoroidal injection. In some embodiments,the vector(s) or pharmaceutical composition are administered via intravitreal injection.The vector(s) or pharmaceutical composition may be administered in any suitable regimen.Suitably, the vector(s) or pharmaceutical composition are administered as a single dose.Suitably, the vector(s) are administered at a dose of at least about 1E10 vg / mL, at least about1E11 vg / mL, at least about 1E12 vg / mL, or at least about 5E12 vg / mL. Suitably, the vector(s)are administered at a dose of at least about 1E9 vg / eye, at least about 1E10 vg / eye, or atleast about 1E11 vg / eye. Suitably, the vector(s) are administered at a dose of about 1E9vg / eye to about 5E12 vg / eye.In another aspect, the present invention provides a kit comprising: (a) a TNF inhibitor, or apolynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same.In another aspect, the present invention provides a pharmaceutical composition comprising:(a) a TNF inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same;and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding thesame.In another aspect, the present invention provides a product comprising: (a) a TNF inhibitor, ora polynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same, as a combined preparation for simultaneous, separate or sequential use in preventing or treating an inflammatory eye disease.In another aspect, the present invention provides a method for preventing or treating aninflammatory eye disease, wherein the method comprises administering to a subject in need thereof: (a) a TNF inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same. Suitably, (a) the TNF inhibitor or polynucleotide encoding the same may be administered inthe form of a vector comprising a nucleotide sequence encoding a TNF inhibitor and / or apharmaceutical composition comprising the TNF inhibitor or polynucleotide encoding thesame; and / or (b) the CD3 inhibitor or polynucleotide encoding the same may be administeredin the form of a vector comprising a nucleotide sequence encoding a CD3 inhibitor and / or apharmaceutical composition comprising the CD3 inhibitor or polynucleotide encoding thesame.The inflammatory eye disease may be any inflammatory eye disease. Suitably, theinflammatory eye disease is uveitis. The TNF inhibitor or polynucleotide encoding the sameand / or the CD3 inhibitor or polynucleotide encoding the same may be administered inresponse to relapse of an inflammatory eye disease, particularly wherein the inflammatory eyedisease is uveitis.The TNF inhibitor or polynucleotide encoding the same and the CD3 inhibitor or polynucleotideencoding the same may be administered by any suitable route and in in any suitable regimen.Suitably, the TNF inhibitor or polynucleotide encoding the same and / or the CD3 inhibitor orpolynucleotide encoding the same is administered intraocularly. In some embodiments, theTNF inhibitor or polynucleotide encoding the same and / or the CD3 inhibitor or polynucleotideencoding the same is administered via intravitreal, subretinal, subconjunctival, sub-Tenon’s orsuprachoroidal injection. In some embodiments, the TNF inhibitor or polynucleotide encodingthe same and / or the CD3 inhibitor or polynucleotide encoding the same is administered viaintravitreal injection.The present inventors have also developed therapies for treating or preventing inflammatoryeye diseases, such as uveitis, in which anti-cell activation CD3 inhibitors are delivered to the eye.The inventors have surprisingly demonstrated that a vector encoding a CD3 inhibitor underthe control of an inflammation-inducible promoter may allow for inflammation-inducibleexpression of a CD3 inhibitor in the eye. When expression of the CD3 inhibitor is coupled to an inflammation-inducible promoter, the therapy may therefore provide an adaptable and responsive dose level to prevent or treat inflammatory eye disease. Such a therapy may prevent re-occurrence of inflammation and / or maintain inflammation at a sub-clinical level, thereby preventing cumulative damage, whilst reducing the occurrence of adverse events imparted by long term systemic immunosuppression.The inventors have also surprisingly demonstrated that intraocular administration of a CD3inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same, may beused to suppress ocular inflammation. Such a therapy may therefore be suitable to prevent ortreat inflammatory eye disease.In one aspect, the present invention provides a CD3 inhibitor, a polynucleotide comprising anucleotide sequence encoding a CD3 inhibitor, or a vector comprising a nucleotide sequenceencoding a CD3 inhibitor.In preferred embodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereof.Any suitable anti-CD3 antibody or fragment thereof may be used. In some embodiments, theCD3 inhibitor is any of foralumab or a fragment thereof, teplizumab or a fragment thereof,visilizumab or a fragment thereof, otelixizumab or a fragment thereof, muromonab-CD3 or afragment thereof, T3 / 4.A or a fragment thereof, YTH12.5 or a fragment thereof, or HuM291 ora fragment thereof. In some embodiments, the CD3 inhibitor is foralumab or a fragmentthereof, teplizumab or a fragment thereof, visilizumab or a fragment thereof, or otelixizumab or a fragment thereof.In some embodiments, the CD3 inhibitor is an anti-CD3 antibody fragment. Any suitable anti-CD3 antibody fragment may be used. In some embodiments, the anti-CD3 antibody fragmentis an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a single chain antibody(scFv), or a single-domain antibody (sdAb). In some embodiments, the anti-CD3 antibodyfragment is an antigen-binding fragment (Fab). In some embodiments, the CD3 inhibitor is anantigen binding fragment (Fab) of foralumab, teplizumab, visilizumab, or otelixizumab.In some embodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereofcomprising one or more CDR regions selected from: (a) SEQ ID NOs: 70 to 75 or derivativesthereof comprising one amino acid substitution; (b) SEQ ID NOs: 81 to 86 or derivativesthereof comprising one amino acid substitution; (c) SEQ ID NOs: 92 to 97 or derivativesthereof comprising one amino acid substitution; or (d) SEQ ID NOs: 103 to 108 or derivativesthereof comprising one amino acid substitution. In some embodiments, the CD3 inhibitor is ananti-CD3 antibody or a fragment thereof comprising: (a) CDR regions HCDR1, HCDR2,HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs: 70, 71, 72, 73, 74and 75 respectively, or derivatives thereof comprising one amino acid substitution; (b) CDRregions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQID NOs: 81, 82, 83, 84, 85 and 86 respectively, or derivatives thereof comprising one aminoacid substitution; (c) CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3comprising or consisting of SEQ ID NOs: 92, 93, 94, 95, 96 and 97 respectively, or derivativesthereof comprising one amino acid substitution; or (d) CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs: 103, 104, 105, 106, 107and 108 respectively, or derivatives thereof comprising one amino acid substitution.In some embodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereofcomprising: (a) a heavy chain comprising or consisting of a sequence with at least 70% identityto SEQ ID NO: 76 and / or a light chain comprising or consisting of a sequence with at least70% identity to SEQ ID NO: 77; (b) a heavy chain comprising or consisting of a sequence withat least 70% identity to SEQ ID NO: 87 and / or a light chain comprising or consisting of asequence with at least 70% identity to SEQ ID NO: 88; (c) a heavy chain comprising orconsisting of a sequence with at least 70% identity to SEQ ID NO: 98 and / or a light chaincomprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 99; or (d) aheavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:109 and / or a light chain comprising or consisting of a sequence with at least 70% identity toSEQ ID NO: 110.In some embodiments: (a) the heavy chain is encoded by a nucleotide sequence having atleast 70% identity to SEQ ID NO: 125 and / or the light chain is encoded by a nucleotidesequence having at least 70% identity to SEQ ID NO: 126; (b) the heavy chain is encoded bya nucleotide sequence having at least 70% identity to SEQ ID NO: 127 and / or the light chainis encoded by a nucleotide sequence having at least 70% identity to SEQ ID NO: 128; (c) theheavy chain is encoded by a nucleotide sequence having at least 70% identity to SEQ ID NO:129 and / or the light chain is encoded by a nucleotide sequence having at least 70% identityto SEQ ID NO: 130; or (d) the heavy chain is encoded by a nucleotide sequence having atleast 70% identity to SEQ ID NO: 131 and / or the light chain is encoded by a nucleotidesequence having at least 70% identity to SEQ ID NO: 132. The nucleotide sequence encodingthe heavy chain and the nucleotide sequence encoding the light chain may be connected viaa linker sequence. Suitably, the linker sequence encodes a 2A self-cleaving peptide, and / oran enzymatically cleavable peptide motif. In some embodiments, the linker sequence encodes a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9. The nucleotide sequence encoding the heavy chain and / or the nucleotide sequence encodingthe light chain may each be operably linked to a signal sequence. In some embodiments, thesignal sequence encodes a signal peptide selected from any of: a Human Growth Hormone (HGH) signal peptide, an interleukin-2 (IL-2) signal peptide, a CD5 signal peptide, an immunoglobulin Kappa light chain signal peptide, a trypsinogen signal peptide, a serum albumin signal peptide, and a prolactin signal peptide.In some embodiments, the nucleotide sequence encoding a CD3 inhibitor encodes an anti-CD3 antibody or a fragment comprising or consisting of: (a) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 76, optionally a 2A self- cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 77; (b) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 87, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any ofSEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70%identity to SEQ ID NO: 88; (c) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 98, optionally a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 99; or (d) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 109, optionally a 2A self- cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs: 6-9, and a lightchain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 110. Insome embodiments, the nucleotide sequence encoding a CD3 inhibitor encodes an anti-CD3antibody or a fragment comprising or consisting of: (a) an amino acid sequence having at least 70% identity to SEQ ID NO: 133; (b) an amino acid sequence having at least 70% identity to SEQ ID NO: 135; (c) an amino acid sequence having at least 70% identity to SEQ ID NO: 137; or (d) an amino acid sequence having at least 70% identity to SEQ ID NO: 139.In some embodiments, the nucleotide sequence encoding a CD3 inhibitor comprises orconsists of: (a) a nucleotide sequence having at least 70% identity to SEQ ID NO: 125, anucleotide sequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, and anucleotide sequence having at least 70% identity to SEQ ID NO: 126; (b) a nucleotidesequence having at least 70% identity to SEQ ID NO: 127, a nucleotide sequence having atleast 70% sequence identity to SEQ ID NO: 10 or 11, and a nucleotide sequence having atleast 70% identity to SEQ ID NO: 128; (c) a nucleotide sequence having at least 70% identityto SEQ ID NO: 129, a nucleotide sequence having at least 70% sequence identity to SEQ IDNO: 10 or 11, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 130; (d)a nucleotide sequence having at least 70% identity to SEQ ID NO: 131, a nucleotide sequencehaving at least 70% sequence identity to SEQ ID NO: 10 or 11, and a nucleotide sequencehaving at least 70% identity to SEQ ID NO: 132. In some embodiments, the nucleotidesequence encoding a CD3 inhibitor comprises or consists of: (a) a nucleotide sequence havingat least 70% identity to SEQ ID NO: 134; (b) a nucleotide sequence having at least 70%identity to SEQ ID NO: 136; (c) a nucleotide sequence having at least 70% identity to SEQ IDNO: 138; or (d) a nucleotide sequence having at least 70% identity to SEQ ID NO: 140. In preferred embodiments, the nucleotide sequence encoding a CD3 inhibitor is operably linked to an inflammation-inducible promoter. Any suitable inflammation-inducible promotermay be used. Suitably, the inflammation-inducible promoter comprises one or moreinflammation-inducible transcription factor binding motif selected from: an AP-1 transcription factor binding motif; a NF-κB transcription factor binding motif; an IRF transcription factor binding motif; a STAT transcription factor binding motif; and a NFAT transcription factor binding motif or any combination thereof.In some embodiments, the inflammation-inducible promoter comprises one or more AP-1binding motif and / or one or more NF-κB binding motif. In some embodiments, theinflammation-inducible promoter comprises two or more AP-1 binding motifs and / or two or more NF-κB binding motifs, three or more AP-1 binding motifs and / or three or more NF-κB binding motifs, four or more AP-1 binding motifs and / or four or more NF-κB binding motifs, or five or more AP-1 binding motifs and / or five or more NF-κB binding motifs. In some embodiments, the inflammation-inducible promoter comprises at least one AP-1 binding motifcoupled to at least one NF-κB binding motif. In some embodiments, the inflammation-induciblepromoter comprises five AP-1 binding motifs coupled to five NF-κB binding motifs. Suitably,an AP-1 binding motif comprises or consists of SEQ ID NO: 151, or comprises or consists ofany of SEQ ID NOs: 152-154 or derivatives thereof comprising one nucleotide substitution.Suitably, a NF-κB binding motif comprises or consists of SEQ ID NO: 155, or comprises orconsists of SEQ ID NO: 156 or a derivative thereof comprising two or fewer nucleotidesubstitutions. In some embodiments, the inflammation-inducible promoter comprises orconsists of a nucleotide sequence having at least 70% identity to SEQ ID NO: 157.In some embodiments, the vector comprises: (a) a nucleotide sequence having at least 70%identity to SEQ ID NO: 159; (b) a nucleotide sequence having at least 70% identity to SEQ IDNO: 160; (c) a nucleotide sequence having at least 70% identity to SEQ ID NO: 161; or (d) anucleotide sequence having at least 70% identity to SEQ ID NO: 162. The vector may comprise any other suitable vector elements. The nucleotide sequenceencoding the CD3 inhibitor may be operably linked to a polyadenylation sequence. Suitably,the polyadenylation sequence is selected from any of: a bovine growth hormone (bGH)polyadenylation sequence, a SV40 polyadenylation sequence, and a rabbit beta-globinpolyadenylation sequence. In some embodiments, the polyadenylation sequence comprisesor consists of a nucleotide sequence having at least 70% identity to SEQ ID NO: 163. Thenucleotide sequence encoding the CD3 inhibitor may be operably linked to a woodchuckhepatitis post-transcriptional regulatory element (WPRE). In some embodiments, the WPREcomprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO:164. The nucleotide sequence encoding the CD3 inhibitor may be operably linked to an intron.Suitably, the intron is selected from a beta-globin intron or a SV40 intron. In someembodiments, the intron comprises or consists of a nucleotide sequence having at least 70%identity to SEQ ID NO: 165. In preferred embodiments, the vector is a viral vector. Any suitable viral vector may be used. Suitably, the viral vector is any of a parvoviral vector, preferably an adeno-associated virus (AAV) vector, an adenoviral vector, a herpes simplex viral vector, an anelloviral vector, a retroviral vector or a lentiviral vector.In preferred embodiments, the vector is an adeno-associated virus (AAV) vector. In preferredembodiments, the vector is an AAV vector particle. The AAV vector particle may bepseudotyped to confer ocular tissue tropism. Suitably, the AAV vector particle comprises AAV2capsid proteins or AAV2 capsid variant proteins, optionally wherein the AAV2 capsid variantis selected from any of: AAV2.tYF, AAV2.7m8, R100, AAV2.GL and AAV2.NN. The vectormay comprise one or more inverted terminal repeats (ITRs).In some embodiments, the vector comprises or consists of: (a) a nucleotide sequence having at least 70% identity to SEQ ID NO: 183; (b) a nucleotide sequence having at least 70% identity to SEQ ID NO: 184; (c) a nucleotide sequence having at least 70% identity to SEQ ID NO: 185; or (d) a nucleotide sequence having at least 70% identity to SEQ ID NO: 186.In another aspect, the present invention provides a vector comprising or consisting of: (a) anucleotide sequence having at least 70% identity to SEQ ID NO: 183; (b) a nucleotide sequence having at least 70% identity to SEQ ID NO: 184; (c) a nucleotide sequence having at least 70% identity to SEQ ID NO: 185; or (d) a nucleotide sequence having at least 70%identity to SEQ ID NO: 186. The vector may be a viral vector. The vector may be an AAVvector.In another aspect, the present invention provides a cell comprising the vector of the presentinvention. The cell may be an isolated cell.In another aspect, the present invention provides a kit for the production of the vector of thepresent invention. In another aspect, the present invention provides a pharmaceutical composition comprisingthe vector of the present invention or the cell of the present invention. The vector or cell maybe in combination with a pharmaceutically acceptable carrier, diluent or excipient. In another aspect, the present invention provides a vector according to the present invention,a cell according to the present invention, and / or a pharmaceutical composition according tothe present invention, for use as a medicament. In another aspect, the present invention provides use of a vector according to the presentinvention, a cell according to the present invention, or a pharmaceutical composition accordingto the present invention, for the manufacture of a medicament. In another aspect, the present invention provides a method comprising administering a vectoraccording to the present invention, a cell according to the present invention, or apharmaceutical composition according to the present invention, to a subject in need thereof. In another aspect, the present invention provides a vector for use in preventing or treating an inflammatory eye disease, wherein the vector comprises a nucleotide sequence encoding aCD3 inhibitor.In another aspect, the present invention provides use of a vector in the manufacture of amedicament for preventing or treating an inflammatory eye disease, wherein the vectorcomprises a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a method for preventing or treating an inflammatory eye disease, wherein the method comprises administering a vector to a subject in need thereof, wherein the vector comprises a nucleotide sequence encoding a CD3 inhibitor.In another aspect, the present invention provides a vector according to the present invention,or a pharmaceutical composition according to the present invention, for use in preventing or treating an inflammatory eye disease.In another aspect, the present invention provides use of a vector according to the presentinvention, or a pharmaceutical composition according to the present invention, for themanufacture of a medicament for preventing or treating an inflammatory eye disease. In another aspect, the present invention provides a method of preventing or treating aninflammatory eye disease comprising administering a vector according to the presentinvention, or a pharmaceutical composition according to the present invention, to a subject in need thereof. In another aspect, the present invention provides a CD3 inhibitor, or a polynucleotidecomprising a nucleotide sequence encoding the same, for use in preventing or treating aninflammatory eye disease. In another aspect, the present invention provides use of a CD3 inhibitor, or a polynucleotidecomprising a nucleotide sequence encoding the same, in the manufacture of a medicamentfor preventing or treating an inflammatory eye disease. In another aspect, the present invention provides a method for preventing or treating an inflammatory eye disease, wherein the method comprises administering a CD3 inhibitor, or apolynucleotide comprising a nucleotide sequence encoding the same, to a subject in needthereof. The CD3 inhibitor or polynucleotide may be administered in the form of a vector comprising anucleotide sequence encoding a CD3 inhibitor and / or a pharmaceutical compositioncomprising the CD3 inhibitor or polynucleotide.The inflammatory eye disease may be any inflammatory eye disease. Suitably, theinflammatory eye disease is uveitis. The CD3 inhibitor, polynucleotide, vector orpharmaceutical composition may be administered in response to relapse of an inflammatoryeye disease, particularly wherein the inflammatory eye disease is uveitis.The CD3 inhibitor, polynucleotide, vector or pharmaceutical composition may be administered by any suitable route. Suitably, the CD3 inhibitor, polynucleotide, vector or pharmaceuticalcomposition is administered intraocularly. In some embodiments, the CD3 inhibitor,polynucleotide, vector or pharmaceutical composition is administered via intravitreal,subretinal, subconjunctival, sub-Tenon’s or suprachoroidal injection. In some embodiments,the CD3 inhibitor, polynucleotide, vector or pharmaceutical composition is administered via intravitreal injection. The CD3 inhibitor, polynucleotide, vector or pharmaceutical composition may be administeredin any suitable regimen. Suitably, the CD3 inhibitor, polynucleotide, vector or pharmaceuticalcomposition is administered as a single dose. Suitably, the vector is administered at a dose ofat least about 1E10 vg / mL, at least about 1E11 vg / mL, at least about 1E12 vg / mL, or at leastabout 5E12 vg / mL. Suitably, the vector is administered at a dose of at least about 1E9 vg / eye,at least about 1E10 vg / eye, or at least about 1E11 vg / eye. Suitably, the vector is administeredat a dose of about 1E9 vg / eye to about 5E12 vg / eye. BRIEF DESCRIPTION OF DRAWING Figure 1: Local administration of an anti-TNF antibody supresses Experimental Autoimmune Uveoretinitis (EAU)B10.RIII mice were immunized for Experimental Autoimmune Uveoretinitis (EAU) and eyesmonitored using Topical Endoscopic Fundal Imaging (TEFI) from day 10 onward to select experimental mice displaying clinically evident disease. Groups of mice were injected via intravitreal route with 15 µg infliximab or vehicle control (EAU) on day 10. Eyes wereenucleated (day 14), and retinal infiltrate characterized. (A) Representative fundus images,(B) clinical disease scores and (C) flow cytometric analysis of total CD45+ cell numbers fromsingle eyes at day 14. **P < 0.005; Data presented as means + / - SEM, representative of twoindependent experiments. Figure 2: Therapeutic vector design Schematic showing the vector organization of CMV.Infliximab Fab (expression under control of a constitutive CMV promoter) and AP1-NFkB.Infliximab Fab (expression under control ofan inflammation-inducible promoter comprised of 5 repeated AP1 and NFkB binding sites).The heavy and light chains of Infliximab Fab are separated by a self-cleaving 2A peptide. Figure 3: Constitutive therapeutic transgene expression(A) HEK-293T (standard cell line for AAV development) or ARPE-19 (ocular cell line) cellswere transduced with AAV2.CMV.Infliximab or AAV.CMV.NULL vectors [MOI 1E5vg / cell], and culture supernatants assayed using a clinical IFX ELISA kit. Detectable expression of Infliximab Fab from both cell types was evident by 72hrs (~30ng / ml). ****P < 0.0001. Datapresented as means + / - SEM. (B) AAV2.CMV.Infliximab or AAV.CMV.NULL was administeredby intravitreal (IVT) injection at 5E12 vg / ml into eyes of healthy B10.RIII mice. At 4wks post- AAV, mice were killed, eyes dissected and supernatants (retina and vitreous) assayed using the clinical IFX ELISA kit. Detectable expression of in vivo Infliximab Fab (~1.5ng / ml) observedin eyes receiving the 5E12 vg / ml dose. *P<0.05. Data presented as means + / - SEM, with eachdata point representing a single eye. Figure 4: In vitro inducible transgene expression HEK-293T cells transduced with AAV2.AP1-NFkB.EGFP (reporter vector) or AAV2.AP1-NFkB.Infliximab (therapeutic vector) were stimulated with recIL-1b (2ng / mL). (A) Activationleads to visible GFP expression at 24hs, increasing in intensity by 72hrs, with no GFP signal observed with AAV2.AP1-NFkB.NULL (control vector). Images captured on EVOS FL, 10Xmagnification. (B) Stimulation results in a rapid induction of Infliximab Fab expression (8hrs),accumulation reaching ~20ng / ml at 72hrs. ****P < 0.0001; Data presented as means + / - SEM. Figure 5: In vivo inducible transgene expression AAV2.AP1-NFkB.EGFP (reporter) or AAV.AP1-NFkB.NULL (control) at a 5E12 vg / ml dosewas administered by intravitreal (IVT) injection to C57BL / 6J mice. (A) At 4wks post-AAVinjection, mice were immunized to induce experimental autoimmune uveoretinitis (EAU), and imaged to monitor onset of ocular inflammation. At day 14 EAU, representative fundus and OCT images demonstrate clear clinical signs of disease (perivascular sheathing and vitreous infiltrate), and induction of GFP expression. In mice that only received AAV (no EAU), noclinical signs of disease or expression of the GFP transgene are observed. (B) Groups of micewere injected with AAV2.AP1-NFkB.Infliximab or AAV2.AP1-NFkB.NULL in the contralateral eye, and EAU induced at 4wks post-AAV. At 3wks post-EAU, mice were killed, eyes dissected and supernatants (retina and vitreous) assayed using the clinical IFX ELISA kit. Detectable expression of the Infliximab Fab is only observed in EAU eyes receiving the therapeutic vectorand not the control. *P<0.05. Data presented as means + / - SEM, with each data pointrepresenting a single eye.Figure 6: In vivo evaluation of constitutive therapeutic transgene efficacyTo demonstrate efficacy of the constitutive therapeutic transgene, groups of mice were injected with AAV7m8.CMV.Infliximab or AAV7m8.CMV.NULL in the contralateral eye, followed by intravitreal administration of recombinant human TNF (rec_hTNF) at 4wks post- AAV. At 18hrs (peak of inflammatory response to rec_hTNF), representative fundus and OCT images demonstrate increased inflammation (vitreous infiltrate) in the control (NULL) vs infliximab eyes (A). In mice that only received AAV, no clinical signs of disease are observed.At 18hrs mice were killed, eyes dissected prepared for flow cytometric analysis to determineabsolute numbers of Ly6C+ monocytes (predominant infiltrate in this model) from single eyes. A significant reduction in number of monocytes in eyes receiving the therapeutic vector and not the control (B), this effect is further highlighted further with paired (contralateral eye) analysis (C). **Wilcoxon signed rank test; *P<0.05 Wilcoxon matched pairs analysis.Figure 7: Constitutive expression of other anti-TNF biologics in vitro and in vivoHEK-293T cells were transfected with the huTNFRI-huIgG plasmid, and culture supernatantsassayed using an anti-human TNF antibody ELISA kit. Detectable expression of huTNFRI-huIgG was evident by 48hrs (A). HEK-293T cells were transduced with AAV7m8.CMV.huTNFRI-huIgG or AAV7m8.CMV.NULL vectors [MOI 1E5vg / cell], and culture supernatants assayed using an anti-human TNF antibody ELISA kit. Detectable expressionwas evident by 72hrs (~30ng / ml) (B). ****P < 0.0001. Data presented as means + / - SEM.AAV7m8.CMV.huTNFRI-huIgG or AAV7m8.CMV.NULL was administered by intravitreal (IVT)injection at range of doses [2E8 or 2E9 vg / eye] into the eyes of healthy C57BL / 6J mice. At4wks post-AAV, mice were killed, eyes dissected and supernatants (retina and vitreous) assayed using the anti-human TNF antibody ELISA kit. Detectable expression of huTNFRI-huIgG at ~4ng / ml and 9ng / ml was observed in eyes receiving 2E8 and 2E9 vg / eye dosesrespectively (C). ns – not significant; One way ANOVA; **P<0.05. Data presented as means+ / - SEM, with each data point representing a single eye.Figure 8: Bioactivity of constitutively expressed anti-TNF transgenes in vitro HEK-BLUE TNF reporter cells were transfected with AAV.CMV.huTNFRI-huIgG, AAV.CMV.huTNFRI-msIgG, AAV.CMV.msTNFRI-msIgG, AAV.CMV.ADALIMUMAB plasmidsor AAV2.CMV.Infliximab for 48hrs. Cells were then stimulated with recombinant human TNFor mouse TNF (0.5ng / ml) for further 24 hours and NFkB activation assessed. All the TNFRIantibody-like plasmid constructs inhibited huTNF- and msTNF-mediated activation in thereporter cell line compared to NULL or recTNF alone (A). For the monoclonal Fab based anti-TNF biologics, plasmid expression of Adalimumab Fab (B) and AAV-mediated Infliximab Fabexpression (8C) both inhibit activation with huTNF.Figure 9: Evaluation of expression and bioactivity of an inducible anti-TNF transgenein vitro HEK-293T cells were transduced with AAV7m8.AP1-NFkB.huTNFRI-huIgG or AAV7m8.AP1-NFkB.NULL vectors [MOI 1E5vg / cell] and stimulated with IL-1b (2ng / ml). Stimulation resultsin robust induction of huTNFRI-huIgG expression by 24hrs, accumulation reaching ~25ng / mlat 48hrs (A). One-way ANOVA; **P<0.0001. Data presented as means + / - SEM. Conditionedmedia was “spiked” with recombinant human or mouse TNF (final concentration 10ng / ml), and incubated with HEK-BLUE reporter cells for 24hrs. In response to both huTNF or mTNFstimulation alone, or with conditioned media from AAV7m8.AP1-NFkB.NULL, NFkB activationis robustly induced in the reporter cells. When supplemented with conditioned media from cellstransduced with AAV7m8.AP1-NFkB.huTNFRI-huIgG and stimulated with IL-1b, NFkBactivation in the reporter cells is completely suppressed (B). One-way ANOVA; **p<0.05***p<0.001; Data presented as means + / - SEM.Figure 10: Evaluation of expression and bioactivity of an inducible anti-TNF transgenein vivoB10.RIII mice were injected with AAV7m8.AP1-NFkB.huTNFRI-huIgG, and EAU induced at4wks post-AAV. At day 19 post-EAU, when mild to moderate clinical signs of inflammation(not yet peak disease) were observed, mice were killed, eyes dissected and supernatants (retina and vitreous) assayed using the anti-human TNF antibody ELISA. Clinical disease drove detectable expression of the huTNFRI-huIgG in EAU eyes receiving the therapeutic vector and not the control (AAV only) (A). Mice were injected with AAV7m8.AP1- NFkB.huTNFRI-huIgG and AAV7m8.AP1-NFkB.NULL (contralateral eye control) at2E9vg / eye. At 4wks post-AAV, mice received bilateral administration of recombinant humanTNF (rec_hTNF), 18hrs later were killed, eyes dissected and ocular supernatants (retina and vitreous) assayed for huTNFRI-huIgG expression. Acute activation elicits a significantincrease in expression of the huTNFRI-huIgG compared to the control (B). ****P<0.0001. Datapresented as means + / - SEM, with each data point representing a single eye.Figure 11: Evaluation of inducible therapeutic transgene efficacy in vivo B10.RIII mice were injected with AAV7m8.AP1-NFkB.huTNFRI-IgG or AAV7m8.CMV.NULL[2E9 vg / eye] in contralateral eyes, and then immunized for EAU at 4wks post-AAV. At day 11,representative fundus and OCT images demonstrate increased inflammation in the eyesreceiving the control NULL vector (A). The contralateral eyes of the same three animals, whichreceived the inducible therapeutic vector, showed substantially reduced clinical inflammation, both peri-vascular sheathing and vitreous infiltrate. At this time-point mice were killed, eyesdissected prepared for flow cytometric analysis to determine absolute numbers of CD45+ (allleukocytes), CD3+ (lymphocytes), CD4+ (Th T cells) and CD11b+ (macrophages andmonocytes) populations from single eyes (B). We observed a trend of reduction in immunecell infiltrates with AAV7m8.AP1-NFkB.huTNFRI-IgG compared to AAV7m8.CMV.NULL.Figure 12: Efficacy of AAV.CMV.msTNFRI-msIgG in EAUC57BL / 6J mice injected with AAV7m8.CMV.msTNFRI-msIgG in one eye, and withAAV7m8.CMV.NULL in contralateral eye, were immunized for Experimental AutoimmuneUveoretinitis (EAU) at 4wks post-AAV. (A) At day 18, clinical imaging demonstratesinflammation (peri-vascular sheathing and vitreous infiltrate) only in the eyes receiving the NULL vector; contralateral eyes receiving the therapeutic transgene appear normal with noclinical signs of disease. (B) FACS analysis of immune cell infiltrate from individual eyes (n=21eyes / group combined from 2 independent experiments), demonstrates a significant reduction in CD45+ cells treated with AAV7m8.CMV.msTNFRI-msIgG compared toAAV7m8.CMV.NULL, confirmed through paired analysis which shows reduced lymphocyte(CD3+) and myeloid (CD11b+) cell counts [***p=0.0002, n=21, two tailed test].Figure 13: Evaluation of anti-CD3 Fab antibody to reduce inflammation in the EAUmodel Mice received a single intravitreal injection of 6ug Anti-CD3 Fab, with vehicle (PBS) administered to the contralateral eye. At day 14 (peak disease in the B10.RIII EAU model), mice were imaged and then killed, eyes dissected and immune cell infiltrate immunophenotyped using FACS. (A) Representative clinical images (Fundus and OCT) demonstrate clinical inflammation in control (PBS) eyes compared to eyes receiving anti-CD3Fab. (B) FACS analysis of immune cell infiltrate from individual eyes demonstratessubstantially reduced CD45+ cell counts [One-way ANOVA, ** p=0.0021, n=6].Figure 14: Therapeutic vector designSchematic showing the organization of vectors comprising constitutive (CMV promotor) orinflammation-inducible promoter (AP1-NFkB; inflammation responsive promotor comprised ofx5 repeated AP1 & NFkB binding sites) expressing: (A) TNFRI-IgG; (B) Anti-CD3 Fab; (C)TNFRI-IgG and Anti-CD3 Fab.Figure 15: Evaluation of constitutive anti-CD3 Fab transgene expression & bioactivityin vitro(A) SDS-PAGE image showing HA-positive 22kD protein band (lanes 1-3), which correspondsto the expected light chain fragment of the anti-CD3 Fab (which includes the HA-tag sequence on the C-terminus). No band was detected in supernatants collected from AAV.CMV.NULLtransfected cells (lanes 4-6). (B) CD4+ T cell proliferation response by FACS. Incubation ofsplenocytes with anti-CD3 FAB antibody (2c11b; positive control) demonstrates suppressed proliferation, in a dose-dependent manner (0.01-1ug / ml). Compared to control (media only)or supernatant from AAV.NULL transfected HEK293T cells, conditioned media fromAAV.CMV.anti-CD3 FAB also significantly reduces CD4+ proliferation.Figure 16: Evaluation of combined targeting therapy (AAV.CMV.msTNFRI-msIgG +AAV.CMV.anti-CD3 Fab) to suppress inflammation in EAUC57BL / 6J mice were injected with (i) AAV7m8.CMV.msTNFRI-msIgG [2E9 vg / eye] or (ii) AAV“MIX” containing AAV7m8.CMV.msTNFRI-msIgG [2E9 vg / eye] + AAV7m8.CMV.anti-CD3FAB [2E9 vg / eye] in one eye, with AAV7m8.CMV.NULL [4E9 vg / eye] in contralateral eye, andwere then immunized for EAU at 4wks post-AAV. (A) At day 18, clinical imaging demonstratesinflammation (peri-vascular sheathing and vitreous infiltrate) only in the eyes receiving the NULL vector; contralateral eyes receiving either the combined “MIX” therapeutic transgenes or AAV.CMV.TNFRI vector only appear normal with no clinical signs of disease. FACSanalysis of immune cell infiltrate from individual eyes of the (B) AAV.TNFRI only treatmentgroup, with 31% reduction in the average (mean) number of CD45+ cells / eye [**p=0.0039,n=9, two tailed test]; and (C) AAV “MIX” treatment group, with 63% reduction in the average(mean) number of CD45+ cells [***p=0.0005, n=13, two tailed test].Figure 17: Evaluation of constitutive anti-CD3 Fab transgene expression & bioactivityfrom ARPE-19 (ocular cell line) in vitro(A) A non-reducing SDS-PAGE image showing HA-positive protein band (lanes 1-3), whichcorresponds to the expected light chain fragment of the anti-CD3 Fab (which includes the HA- tag sequence on the C-terminus). No band was detected in supernatants collected from AAV.CMV.NULL transfected cells (lanes 4-6). (B) CD4+ T cell proliferation response by FACS. Incubation of splenocytes with anti-CD3 FAB antibody (2c11b; positive control) demonstrates suppressed proliferation, in a dose-dependent manner (0.005-5ug / ml). Compared to control (media only) or supernatant from AAV.NULL transfected ARPE-19 cells, conditioned media from AAV.CMV.anti-CD3 Fab also significantly reduces CD4+ proliferation, comparable to 0.05ug / ml 2c11b control. Figure 18: Evaluation of inducible anti-CD3 Fab transgene expression in vitro ARPE-19 cells were transduced with AAV7m8.AP1-NFkB.anti-CD3 Fab or AAV7m8.AP1- NFkB.NULL vectors [MOI 1E5vg / cell] and stimulated with IL-1b (2ng / ml). Conditioned media was collected at 0, 24 & 48hrs, and concentrated for SDS-PAGE. Stimulation results in robust induction of anti-CD3 Fab expression evident at 24hrs (lanes 4-6) and 48hrs (lanes 1-3), shown by HA-positive protein band, corresponding to the expected light chain fragment of the anti-CD3 Fab (which includes the HA-tag sequence on the C-terminus). No band is observed at 0hrs (lanes 7-9) or NULL (lanes 10-11). Figure 19: Efficacy of AAV.CMV.anti-CD3 Fab in EAU C57BL / 6J mice were injected in both eyes with AAV7m8.CMV.anti-CD3 Fab (n=7 eyes) or AAV7m8.CMV.NULL (n=3 eyes) [Vector dose: 4E9 vg / eye], and were immunized forExperimental Autoimmune Uveoretinitis (EAU) at 4wks post-AAV. (A) At day 18, clinicalimaging demonstrates inflammation (peri-vascular sheathing and vitreous infiltrate) in the eyes receiving the NULL vector; eyes receiving the therapeutic transgene show only mild clinicalsigns of disease. (B) FACS analysis of immune cell infiltrate from individual eyes (n=3-7eyes / group), demonstrates lower numbers of CD45+ and CD3+ cell populations treated with AAV7m8.CMV.anti-CD3 Fab compared to AAV7m8.CMV.NULL. (C) AAV7m8.CMV.2c11b treatment promotes an exhausted CD3+ phenotype, shown by increased expression of CTLA- 4 and TIM-3. Figure 20: Evaluation of constitutive expression of two transgenes (TNFRI-IgG and Anti-CD3 Fab) from bi-cistronic plasmid in vitro ARPE-19 cells were transfected with AAV.CMV.anti-CD3 Fab, AAV.CMV.NULL or AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab) plasmids (1ug / ml), and incubated for 72hrs. (A) Conditioned media (CM) was collected and “spiked” with recombinant mouse TNF (final concentration 0.1ng / ml), before incubation with HEK-BLUE reporter cells for 24hrs, for NFkB activation assessment. CM from AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab (Bi-cistronic plasmid) inhibited mTNF-mediated activation in the reporter cell line compared to NULL or recTNF alone, indicating expression of bioactive msTNFRI-msIgG transgene from the bi-cistronic plasmid. One-way ANOVA; ****p<0.0001; Data presented as means + / - SEM. (B)CM from AAV.CMV.anti-CD3 Fab, AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab orAAV.CMV.NULL was resolved by SDS-PAGE using non-reducing conditions. Image showsHA-positive protein band (light chain fragment of the anti-CD3 Fab) present in the AAV.CMV.anti-CD3 Fab and AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab samples. No band was detected in supernatants collected from AAV.CMV.NULL. This demonstrates expression of the anti-CD3 Fab transgene from the bi-cistronic plasmid. Figure 21: Evaluation of constitutive expression of two transgenes (TNFRI-IgG and Anti-CD3 Fab) from bi-cistronic AAV in vitro HEK293T or ARPE-19 cells were transduced with AAV7m8.CMV.msTNFRI-IgG, AAV7m8.CMV.anti-CD3 Fab, AAV7m8.CMV.NULL or AAV7m8.CMV.msTNFRI-msIgG.anti-CD3 Fab vectors [MOI 1E5vg / cell], and incubated for 48hrs. (A) Conditioned media (CM) wascollected and “spiked” with recombinant mouse TNF (final concentration 0.1ng / ml), before incubation with HEK-BLUE reporter cells for 24hrs, and NFkB activity assessed. CM from AAV7m8.CMV.msTNFRI-msIgG and AAV7m8.CMV.msTNFRI-msIgG.anti-CD3 Fab transfected HEK293T or ARPE-19 inhibited mTNF-mediated activation in the reporter cell line compared to NULL, and confirms expression of bioactive msTNFRI-msIgG transgene from bi-cistronic AAV. One-way ANOVA; ****p<0.0001; Data presented as means + / - SEM. (B)HEK293T CM from AAV.CMV.anti-CD3 Fab, AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab orAAV.CMV.NULL was resolved by SDS-PAGE (non-reducing conditions). Image shows HA- positive protein band (light chain fragment of the anti-CD3 Fab) present in the AAV.CMV.anti- CD3 Fab and AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab samples only. No band was detected in supernatants collected from AAV.CMV.NULL. This demonstrates expression of the anti- CD3 Fab transgene from the bi-cistronic AAV vector. Figure 22: Evaluation of combined targeting therapy (AAV.CMV.msTNFRI-msIgG + AAV.CMV.anti-CD3 Fab) to maintain reduced inflammation post-peak EAU C57BL / 6J mice were injected with AAV “MIX” containing AAV7m8.CMV.msTNFRI-msIgG [2E9 vg / eye] + AAV7m8.CMV.anti-CD3 Fab [2E9 vg / eye] in one eye, with AAV7m8.CMV.NULL [4E9 vg / eye] in contralateral eye, and were then immunized for EAU at4wks post-AAV. (A) At day 28, clinical imaging demonstrates inflammation (peri-vascularsheathing and vitreous infiltrate) in eyes receiving the NULL vector; contralateral eyes receiving the combined “MIX” therapeutic transgenes only show mild clinical signs of disease.(B) FACS analysis of immune cell infiltrate from individual eyes of the AAV “MIX” vs NULLeyes, shows 34% reduction in the average (mean) number of CD45+ cells [**p=0.005, n=7, paired t test]. Figure 23: Evaluation of bi-cistronic AAV.CMV.msTNFRI-msIgG.anti-CD3 Fab to suppress inflammation in EAU C57BL / 6J mice injected with AAV7m8.CMV.msTNFRI-msIgG.anti-CD3 Fab in one eye, and with AAV7m8.CMV.NULL in contralateral eye, were immunized for Experimental AutoimmuneUveoretinitis (EAU) at 4wks post-AAV. (A) At day 18, clinical imaging demonstratesinflammation (peri-vascular sheathing and vitreous infiltrate) only in the eyes receiving the NULL vector; contralateral eyes receiving the therapeutic transgenes appear normal with noclinical signs of disease. (B) FACS analysis of immune cell infiltrate from individual eyes (n=8eyes / group), demonstrates a significant reduction in CD45+ cells treated with AAV7m8.CMV.msTNFRI-msIgG.anti-CD3 Fab compared to AAV7m8.CMV.NULL, confirmed through paired analysis which shows reduced lymphocyte (CD3+) and myeloid (CD11b+) cell counts [* p=0.05; **p=0.005, n=8, two tailed test]. Figure 24: Bicistronic plasmids Plasmid maps showing the organization of the bi-cistronic constructs comprising (A)constitutive (CMV promotor) or (B) inflammation-inducible promoter (AP1-NFkB; inflammationresponsive promotors for expression of TNFRI-IgG and Anti-CD3 Fab transgenes. DETAILED DESCRIPTION Various preferred features and embodiments of the present invention will now be described by way of non-limiting examples. It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. The terms "comprising", "comprises" and "comprised of" as used herein are synonymous with "including", "includes", "containing", or "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or steps. The terms "comprising", "comprises" and "comprised of" also include the term "consisting of". Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated,any nucleic acid sequences are written left to right in 5' to 3' orientation and amino acidsequences are written left to right in amino to carboxy orientation, respectively. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that suchpublications constitute prior art to the claims appended hereto. All publications mentioned inthe specification are herein incorporated by reference. This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in thepractice or testing of embodiments of this disclosure. The skilled person will understand thatthey can combine all features of the invention disclosed herein without departing from the scope of the invention as disclosed. CombinationsThe present invention provides a combination of: (a) a TNF inhibitor, or a polynucleotidecomprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or apolynucleotide comprising a nucleotide sequence encoding the same. The combination of the present invention may be provided in any suitable form. In some embodiments, (a) the TNF inhibitor or polynucleotide encoding the same is in the form of avector comprising a nucleotide sequence encoding a TNF inhibitor; and / or (b) the CD3 inhibitoror polynucleotide encoding the same may is in the form of a vector comprising a nucleotide sequence encoding a CD3 inhibitor. In some embodiments, (a) the TNF inhibitor or polynucleotide encoding the same is in the form of a vector comprising a nucleotide sequenceencoding a TNF inhibitor; and (b) the CD3 inhibitor or polynucleotide encoding the same mayis in the form of a vector comprising a nucleotide sequence encoding a CD3 inhibitor.The combination of the present invention may be provided in the form of a bicistronic ormulticistronic vector, two separate vectors, or a product, kit or pharmaceutical compositioncomprising the combination. In some embodiments, the combination of the present inventionmay be provided in the form of a bicistronic or multicistronic vector encoding a TNF inhibitorand a CD3 inhibitor. In other embodiments, the combination of the present invention may beprovided in the form of a vector encoding a TNF inhibitor and a vector encoding a CD3inhibitor. In other embodiments, the combination of the present invention may be provided inthe form of a product, kit, or pharmaceutical comprising: (a) a TNF inhibitor, or a polynucleotidecomprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same. Antibodies and antibody fragments In some embodiments, (a) the TNF inhibitor comprises or consists of an anti-TNF antibody ora fragment thereof; and / or (b) the CD3 inhibitor comprises or consists of an anti-CD3 antibodyor a fragment thereof. In preferred embodiments, (a) the TNF inhibitor comprises or consistsof an anti-TNF antibody or a fragment thereof; and (b) the CD3 inhibitor comprises or consistsof an anti-CD3 antibody or a fragment thereof.In preferred embodiments, (a) the TNF inhibitor is an anti-TNF antibody or a fragment thereof;and / or (b) the CD3 inhibitor is an anti-CD3 antibody or a fragment thereof. In more preferredembodiments, (a)the TNF inhibitor is an anti-TNF antibody or a fragment thereof; and (b) theCD3 inhibitor is an anti-CD3 antibody or a fragment thereof.Antibodies are glycoproteins belonging to the immunoglobulin superfamily. Antibodies aretypically made of basic structural units, each with two heavy chains and two light chains. Anantibody may recognise an antigen via the fragment antigen-binding (Fab) variable region.The fragment crystallizable region (Fc region) is the tail region of an antibody that may allowantibodies to activate the immune system. The hinge region is a stretch of heavy chains linkingthe Fab and Fc regions. The “heavy chain” and “light chain” may each comprise a variable domain and one or more constant domains. For example, in IgG antibodies, a heavy chain comprises a variable domain (VH) and three constant domains (CH1, CH2, and CH3) and a light chain comprises a variable domain (VL) and one constant domain (CL). In some embodiments, for example in an antigen-binding fragment (Fab), a heavy chain comprises one variable domain (VH) and one constantdomain (CH1). In some embodiments, for example in an antigen-binding fragment (Fab), alight chain comprises one variable domain (VL) and one constant domain (CL). “Heavy chain variable region” or “VH” refers to the fragment of the heavy chain of an antibody that contains three CDRs interposed between flanking stretches known as framework regions,which form a scaffold to support the CDRs. “Light chain variable region” or “VL” refers to thefragment of the light chain of an antibody that contains three CDRs interposed between framework regions. “Complementarity determining region” or “CDR” with regard to an antibody or antigen-binding fragment thereof refers to a highly variable loop in the variable region of the heavy chain or the light chain of an antibody. CDRs can interact with the antigen conformation and largely determine binding to the antigen. The heavy chain variable region and the light chain variable region each contain 3 CDRs (heavy chain CDRs 1, 2 and 3 and light chain CDRs 1, 2 and 3, numbered from the amino to the carboxy terminus). The CDRs of the variable regions of a heavy and light chain of an antibody can be predicted from the heavy and light chain variable region sequences of the antibody, using prediction software available in the art, e.g. using the Abysis algorithm, the IMGT / V-QUEST software, orAbRSA (see e.g. Lefranc et al, 2009 NAR 37:D1006-D1012; Lefranc 2003, Leukemia 17: 260-266; and Li, L., et al., 2019. Protein Science, 28(8), pp.1524-1531). CDR regions identified byany algorithm are considered to be equally suitable for use in the invention.CDRs may vary in length, depending on the numbering scheme and the antibody from whichthey are predicted and between the heavy and light chains. Thus, the three heavy chain CDRsof an intact antibody may be of different lengths (or may be of the same length) and the threelight chain CDRs of an intact antibody may be of different lengths (or may be of the samelength). A CDR for example, may range from 2 or 3 amino acids in length to 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acids in length. Particularly, a CDR may be from3-14 amino acids in length, e.g. at least 3 amino acids and less than 15 amino acids. Anysuitable numbering scheme may be used to predict the CDRS, such as Kabat, Chothia, or IMGT numbering schemes (see e.g. Dondelinger, M., et al., 2018. Frontiers in immunology, 9, p.2278). Suitably, the CDRs are predicted using the Kabat numbering scheme In preferred embodiments, (a) the anti-TNF antibody or fragment thereof is an anti-TNFantibody fragment; and / or (b) the anti-CD3 antibody or fragment thereof is an anti-CD3antibody fragment. In more preferred embodiments, (a) the anti-TNF antibody or fragmentthereof is an anti-TNF antibody fragment; and (b) the anti-CD3 antibody or fragment thereofis an anti-CD3 antibody fragment. An “antibody fragment” may be a fragment of an antibody,or a genetically engineered product of one of more fragments of an antibody, which fragmentis involved in binding with the target molecule (e.g. TNF or CD3). Examples include an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a variable region (Fv), a single chainantibody (scFv), a single-domain antibody (sdAb), and a camelid antibody (VHH). The use ofan antibody fragment may be advantageous because it may reduce inflammation associatedwith the Fc region. In some embodiments, the antibody fragment is an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a single chain antibody (scFv), or a single-domain antibody (sdAb). In preferred embodiments, the antibody fragment is an antigen-binding fragment (Fab).“Antigen-binding fragment” (Fab) refers to a region on an antibody that binds to antigens. It iscomposed of one constant and one variable region of each of the heavy and the light chain.In other embodiments, the antibody fragment is a fragment antibody (F(ab’)2). “Fragmentantibody” (F(ab’)2) refers to a region on an antibody that remains following digestion of the Fcregion while leaving intact some of the hinge region. In other embodiments, the antibody fragment is a single chain antibody (scFv). “Single chain antibody” (scFv) refers to an engineered antibody consisting of a light chain variable region and a heavy chain variable region connected to one another directly or via a peptide linker sequence. The peptide linker sequence is usually about 10 to 25 amino acids in length, rich in glycine for flexibility, and serine or threonine for solubility. The peptide linker sequence can either connect the N-terminus of the heavy chain variable region with the C-terminus of the light chain variable region, or vice versa. In other embodiments, the antibody fragment is a single-domain antibody (sdAb). “Single- domain antibody” (sdAb), also known as a nanobody, refers to an antibody fragment consisting of a single monomeric variable antibody domain. Accordingly, a sdAb may be a heavy chain variable region (VH) or a light chain variable region (VL). Examples of single-domain antibodies include, but are not limited to, VHH fragments, and VNAR fragments. Single- domain antibodies may also be generated by splitting the dimeric variable domains from common IgG molecules into monomers. The present invention includes “variants” of the CDR regions described below. The term “variant” as used herein is defined below in the section “Variants, derivatives and fragments”. It will be appreciated that one or more amino acid substitutions may be made in the CDRswhilst retaining the antigen-binding ability. For instance, the CDR variants may comprise 3 orfewer amino acid substitutions, e.g.3 amino acid substitutions, 2 amino acid substitutions or1 amino acid substitution. In particular, in some embodiments the CDR variants comprise oneamino acid substitution and retain the antigen-binding ability. The variant may be a variantwith at least 80% or 90% identity to the CDR. Examples of antibodies, and fragments and / orderivatives thereof that can be used in the invention are further described below. Signal peptidesThe TNF inhibitor and / or CD3 inhibitor may be operably linked to one or more signal peptides.In some embodiments, the TNF inhibitor and / or the CD3 inhibitor is operably linked to one ormore signal peptides. In some embodiments, the TNF inhibitor and the CD3 inhibitor isoperably linked to one or more signal peptides. A “signal peptide” may refer to a short peptide that directs the insertion of proteins into themembrane of the endoplasmic reticulum. Signal peptides are typically N-terminal extensionsof newly synthesized secretory and membrane proteins that are 16 to 30 amino acid residuesin length and comprised of a hydrophilic, usually positively charged N-terminal region, a centralhydrophobic domain, and a C-terminal region with the cleavage site for signal peptidase.Besides these common characteristics, signal peptides do not share sequence similarity andsome are more than 50 amino acid residues long (see e.g. Kapp, K., et al., 2009. Protein transport into the endoplasmic reticulum, pp.1-16).The TNF inhibitor and / or CD3 inhibitor may be operably linked to any suitable signalpeptide(s). The SPdb signal peptide database is a repository of experimentally determinedand computationally predicted signal peptides (see e.g. Choo, K.H., et al., 2005. BMCbioinformatics, 6(1), pp.1-8). Suitable signal peptides include, a Human Growth Hormone (HGH) signal peptide, an interleukin-2 (IL-2) signal peptide, a CD5 signal peptide, an immunoglobulin Kappa light chain signal peptide, a trypsinogen signal peptide, a serumalbumin signal peptide, or a prolactin signal peptide.In some embodiments, the signal peptide is selected from one or more of: a Human GrowthHormone (HGH) signal peptide, an interleukin-2 (IL-2) signal peptide, a CD5 signal peptide, an immunoglobulin Kappa light chain signal peptide, a trypsinogen signal peptide, a serum albumin signal peptide, and a prolactin signal peptide. In some embodiments, the signalpeptide is a Human Growth Hormone (HGH) signal peptide.In some embodiments, the TNF inhibitor is operably linked to one or more Human GrowthHormone (HGH) signal peptide. In some embodiments, the TNF inhibitor is operably linked to one or more signal peptide comprising or consisting of an amino acid sequence having at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 1. In someembodiments the TNF inhibitor is operably linked to one or more signal peptide comprising orconsisting of the amino acid sequence of SEQ ID NO: 1.In some embodiments, the CD3 inhibitor is operably linked to one or more Human GrowthHormone (HGH) signal peptide. In some embodiments, the CD3 inhibitor is operably linked toone or more signal peptide comprising or consisting of an amino acid sequence having at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 1. In someembodiments the CD3 inhibitor is operably linked to one or more signal peptide comprising orconsisting of the amino acid sequence of SEQ ID NO: 1.In some embodiments, (a) the TNF inhibitor is operably linked to one or more Human GrowthHormone (HGH) signal peptide; and (b) the CD3 inhibitor is operably linked to one or moreHuman Growth Hormone (HGH) signal peptide. In some embodiments, (a) the TNF inhibitor is operably linked to one or more signal peptide comprising or consisting of an amino acidsequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQID NO: 1; and (b) the CD3 inhibitor is operably linked to one or more signal peptide comprisingor consisting of an amino acid sequence having at least 70%, at least 75%, at least 80%, atleast 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%identity, or 100% identity to SEQ ID NO: 1. In some embodiments, (a) the TNF inhibitor isoperably linked to one or more signal peptide comprising or consisting of the amino acidsequence of SEQ ID NO: 1; and (b) the CD3 inhibitor is operably linked to one or more signalpeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. MATGSRTSLLLAFGLLCLPWLQEGSA Example HGH signal peptide (SEQ ID NO: 1)Example nucleotide sequencesThe TNF inhibitor and / or CD3 inhibitor may be encoded by any suitable nucleotide sequence.In some embodiments, (a) the nucleotide sequence encoding the TNF inhibitor; and / or (b) thenucleotide sequence encoding the CD3 inhibitor is codon-optimised, for example codon-optimised for expression in humans. In some embodiments, (a) the nucleotide sequenceencoding the TNF inhibitor is codon-optimised, for example codon-optimised for expression inhumans; and (b) the nucleotide sequence encoding the CD3 inhibitor is codon-optimised, forexample codon-optimised for expression in humans. Different cells differ in their usage ofparticular codons. This codon bias corresponds to a bias in the relative abundance of particulartRNAs in the cell type. By altering the codons in the sequence so that they are tailored tomatch with the relative abundance of corresponding tRNAs, it is possible to increase expression. By the same token, it is possible to decrease expression by deliberately choosing codons for which the corresponding tRNAs are known to be rare in the particular cell type. Thus, an additional degree of translational control is available. Codon usage tables are known in the art for mammalian cells (e.g. humans), as well as for a variety of other organisms.Suitably, a nucleotide sequence encoding a Fab may comprise from 5’ to 3’: a first signalsequence; a nucleotide encoding a heavy chain (e.g. VH + CH1); a linker sequence; a secondsignal sequence; and a nucleotide encoding a light chain. Suitably, a nucleotide sequenceencoding a Fab may comprise from 5’ to 3’: a first signal sequence; a nucleotide encoding alight chain; a linker sequence; a second signal sequence; and a nucleotide encoding a heavychain (e.g. VH + CH1).Signal sequencesThe first signal sequence and the second signal sequence may encode the same signalpeptide or different signal peptides. In some embodiments, the first signal sequence and thesecond signal sequence encode the same signal peptide. The first signal sequence and thesecond signal sequence may be any signal sequence described herein.In some embodiments, the first signal sequence and / or the second signal sequence encodeany of: a Human Growth Hormone (HGH) signal peptide, an interleukin-2 (IL-2) signal peptide, a CD5 signal peptide, an immunoglobulin Kappa light chain signal peptide, a trypsinogen signal peptide, a serum albumin signal peptide, and a prolactin signal peptide.In some embodiments, the first signal sequence and / or the second signal sequence encodea Human Growth Hormone (HGH) signal peptide. In some embodiments, the first signalsequence and the second signal sequence encode a Human Growth Hormone (HGH) signal peptide.In some embodiments, the first signal sequence and / or the second signal sequence comprisesor consists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to any of SEQ ID NOs: 2-5. In some embodiments, the first signal sequenceand / or the second signal sequence comprises or consists of the nucleotide sequence of anyof SEQ ID NOs: 2-5. atggcaacaggtagtcgaaccagcctattactggccttcggtctcctgtgtctgccctggct tcaagagggctctgc Example HGH signal sequence (SEQ ID NO: 2)atggccacgggaagtcggacttccttactactcgcctttggtcttctttgcttgccatggct ccaggagggtagtgca Example HGH signal sequence (SEQ ID NO: 3)atggccacaggctctcggaccagcctgctgctggccttcggcctgctgtgtctgccttggct gcaagagggcagcgcc Example HGH signal sequence (SEQ ID NO: 4) atggctaccggcagcagaaccagcctgctgctggcattcggccttctgtgcctgccttggct gcaagagggctctgcc Example HGH signal sequence (SEQ ID NO: 5)Linker sequences The linker sequence may comprise one or more cleavage sites. As used herein, “cleavagesites” may include nucleotide sequences encoding specific peptide sequences at which site-specific proteases may cleave or cut the peptide (also known as enzymatically cleavablepeptide motifs) and nucleotide sequences encoding self-cleaving peptides. In preferred embodiments, the linker sequence encodes a cleavage site. In some embodiments, the linker sequence encodes a self-cleaving peptide and / or an enzymatically cleavable peptide motif. In some embodiments, the linker sequence encodes a 2A self-cleaving peptide. 2A self-cleaving peptides are a class of 18–22 aa-long peptides, which can induce ribosomal skippingduring translation of a protein in a cell. Suitable 2A self-cleaving peptides include T2A, P2A, E2A and F2A, or derivatives thereof.In some embodiments, the linker sequence encodes a 2A self-cleaving peptide having at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99% identity, or 100% identity to any of SEQ ID NOs: 6-9. Insome embodiments, the linker sequence encodes a 2A self-cleaving peptide comprising orconsisting of any of SEQ ID NOs: 6-9.In some embodiments, the linker sequence encodes a 2A self-cleaving peptide having at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 6. In someembodiments, the linker sequence encodes a 2A self-cleaving peptide comprising orconsisting of SEQ ID NO: 6. ATNFSLLKQAGDVEENPGP Example P2A peptide sequence (SEQ ID NO: 6)EGRGSLLTCGDVEENPGP Example T2A peptide sequence (SEQ ID NO: 7)QCTNYALLKLAGDVESNPGP Example E2A peptide sequence (SEQ ID NO: 8)VKQTLNFDLLKLAGDVESNPGP Example F2A peptide sequence (SEQ ID NO: 9) In some embodiments, the linker sequence comprises a nucleotide sequence having at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99% identity, or 100% identity to any of SEQ ID NOs: 10-11. In some embodiments, the linker sequence comprises any of SEQ ID NOs: 10-11. gctacgaatttttcattgctcaagcaagcgggagatgtggaggagaaccctggcccc Example P2A nucleotide sequence (SEQ ID NO: 10)gctaccaacttcagcctcctgaaacaggccggcgatgtggaggaaaaccctggacct Example P2A nucleotide sequence (SEQ ID NO: 11)The linker sequence may comprise any other suitable nucleotide sequences, for examplenucleotide sequences which aid expression. Suitably, the linker sequence may comprise afurin site and / or a fusion protein linker sequence.In some embodiments, the linker sequence comprises a furin site. Furin is a protease enzymethat may cleave at a conserved polybasic RNRR site. Suitably, the furin site encodes RKRR.In some embodiments, the linker sequence comprises fusion protein linker sequence. Fusionprotein linker sequences may join two protein domains together. Suitably, the fusion proteinlinker sequence encodes SGSG.In some embodiments, the linker sequence encodes from 5’ to 3’: a furin site, a fusion protein linker sequence, and a 2A self-cleaving peptide.In some embodiments, the linker sequence encodes an amino acid having at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 12. In some embodiments,the linker sequence encodes an amino acid comprising or consisting of SEQ ID NO: 12.RKRRSGSGATNFSLLKQAGDVEENPGP Example linker peptide sequence (SEQ ID NO: 12)In some embodiments, the linker sequence comprises or consists of a nucleotide sequencehaving at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to any of SEQ ID NOs: 13-14. In some embodiments, the linker sequence comprises or consists of any of SEQ ID NOs: 13-14. aggaagcggcgttccgggagcggggctacgaatttttcattgctcaagcaagcgggagatgt ggaggagaaccctggcccc Example linker sequence (SEQ ID NO: 13)agaaagcggagaagcggaagcggtgctaccaacttcagcctcctgaaacaggccggcgatgt ggaggaaaaccctggacct Example linker sequence (SEQ ID NO: 14) Other sequences The nucleotide sequence encoding may comprise any other suitable sequences. For example,the TNF inhibitor or CD3 inhibitor may be linked to a HA tag for detection. Suitably, an HA tagmay comprise or consist of SEQ ID NO: 15. YPYDVPDYA Example HA tag (SEQ ID NO: 15)TNF inhibitors The combination of the present invention comprises a TNF inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same. As used herein, a “TNF inhibitor” may be any protein or oligonucleotide that suppresses an inflammatory response to TNF. Tumour necrosis factor (TNF) is also known as cachexin orcachectin, and may also be known as tumour necrosis factor alpha (TNF-α). TNF issynthesized as a transmembrane protein (mTNF) and cleaved to soluble TNF (sTNF). Thereare two types of TNF, which are very closely related, TNF-alpha and TNF-beta. The activitiesof both TNFs are mediated through binding to the TNF receptors, TNFR1 and TNFR2. Thebinding of TNF may activate several signalling pathways, including transcription factoractivation, proteases, and protein kinases. This signalling may lead to activation of the targetcell leading to the inflammatory and immune response by releasing several cytokines andapoptotic pathway initiation (see Gerriets, V., et al., 2021. “Tumor necrosis factor inhibitors”.In StatPearls).Example TNF inhibitors include adalimumab, infliximab, golimumab, certolizumab pegol,etanercept, XPro1595, XENP345, R1antTNF, Atrosab, and Atrosimab (see e.g. Lis, K.,Kuzawińska, O. and Bałkowiec-Iskra, E., 2014. AMS, 10(6), p.1175; and Fischer, R., et al., 2020. Frontiers in cell and developmental biology, 8, p.401). Suitably, a TNF inhibitor may inhibit TNF activity by directly binding to TNF. For example, a TNF inhibitor may be an anti- TNF antibody or fragment thereof (e.g. adalimumab, infliximab, golimumab, certolizumab), or comprise the TNF-binding domain of a TNFR receptor (e.g. etanercept). Alternatively, a TNF inhibitor may inhibit TNF activity by binding to a TNF receptor. For example, a TNF inhibitormay be a TNF mutein (e.g. XPro1595, XENP345, R1antTNF) or may be an anti-TNFRantibody or fragment thereof (e.g. Atrosab and Atrosimab).In preferred embodiments, the TNF inhibitor is a human-specific TNF inhibitor, i.e. a proteinor oligonucleotide that suppresses an inflammatory response to human TNF. In someembodiments, the TNF inhibitor is an anti-human TNF antibody or a fragment thereof (e.g.adalimumab, infliximab, golimumab, certolizumab, or fragments thereof).Suitably, a TNF inhibitor may suppress an inflammatory response by binding to TNFα. Forexample, a TNF inhibitor may be an anti-TNFα antibody (e.g. adalimumab, infliximab,golimumab, certolizumab) or a fragment thereof. In some embodiments, the TNF inhibitor isan anti-human TNFα antibody or a fragment thereof (e.g. adalimumab, infliximab, golimumab, certolizumab, or fragments thereof). Anti-TNF antibody or fragment thereof In some embodiments, the TNF inhibitor comprises or consists of an anti-TNF antibody or a fragment thereof. In preferred embodiments, the TNF inhibitor is an anti-TNF antibody or a fragment thereof.The anti-TNF antibody may be a monoclonal antibody (mAb) or a fragment thereof. In someembodiments, the TNF inhibitor is a humanized anti-TNF mAb or a fragment thereof. In someembodiments, the TNF inhibitor is a human anti-TNF mAb or a fragment thereof.Suitable anti-TNF antibodies are known in the art. Moreover, anti-TNF antibodies, andfragments and / or derivatives thereof, can be prepared using methods known by those of skillin the art. Such methods include phage display, methods to generate human or humanized antibodies, or methods using transgenic animal or plant engineered to produce human antibodies. Phage display libraries of partially or fully synthetic antibodies are available and can be screened for an antibody or fragment thereof that can bind to the target molecule. Phage display libraries of human antibodies are also available. Once identified, the amino acid sequence or polynucleotide sequence encoding for the antibody (or fragment and / or derivative thereof) can be isolated and / or determined. The sequence of the antibody can be used to design suitable fragments and / or derivatives thereof. In preferred embodiments, the anti-TNF antibody or fragment thereof is an anti-TNF antibodyfragment. An “anti-TNF antibody fragment” may be a fragment of an anti-TNF antibody, or agenetically engineered product of one of more fragments of the anti-TNF antibody, whichfragment is involved in binding with TNF. In some embodiments, the anti-TNF antibodyfragment is an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a single chain antibody (scFv), or a single-domain antibody (sdAb). In preferred embodiments, the anti-TNF antibody fragment is an antigen-binding fragment (Fab).The TNF inhibitor may comprise at least one CDR (e.g. HCDR3), which can be predicted froman anti-TNF antibody (or a variant of such a predicted CDR e.g. a variant with one, two orthree amino acid substitutions). It will be appreciated that molecules containing three or fewerCDR regions (e.g. a single CDR or even a part thereof) may be capable of retaining the antigen-binding activity of the antibody from which the CDR is derived. Molecules containing two CDR regions are described in the art as being capable of binding to a target antigen, e.g. in the form of a minibody (see e.g. Vaughan and Sollazzo, 2001, Combinational Chemistry & High Throughput Screening, 4, 417-430). Molecules containing a single CDR have been described which can display strong binding activity to target (see e.g. Nicaise et al, 2004, Protein Science, 13: 1882-91). The TNF inhibitor may comprise one or more variable heavy chain CDRs, e.g. one, two orthree variable heavy chain CDRs. Alternatively, or additionally, the TNF inhibitor may compriseone or more variable light chain CDRs, e.g. one, two or three variable light chain CDRs. TheTNF inhibitor may comprise three heavy chain CDRs and / or three light chain CDRs (and moreparticularly a heavy chain variable region comprising three CDRs and / or a light chain variableregion comprising three CDRs) wherein at least one CDR, preferably all CDRs, may be from an anti-TNF antibody, or may be selected from one of the CDR sequences provided below.The TNF inhibitor may comprise any combination of variable heavy and light chain CDRs, e.g.one variable heavy chain CDR together with one variable light chain CDR, two variable heavy chain CDRs together with one variable light chain CDR, two variable heavy chain CDRs together with two variable light chain CDRs, three variable heavy chain CDRs together with one or two variable light chain CDRs, one variable heavy chain CDR together with two or three variable light chain CDRs, or three variable heavy chain CDRs together with three variablelight chain CDRs. Preferably, the TNF inhibitor comprises three variable heavy chain CDRs(HCDR1, HCDR2 and HCDR3) and / or three variable light chain CDRs (LCDR1, LCDR2 and LCDR3).The one or more CDRs present within the TNF inhibitor may not all be from the same antibody,as long as the domain has the binding activity described above. Thus, one CDR may be predicted from the heavy or light chains of an anti-TNF antibody, whilst another CDR presentmay be predicted from a different anti-TNF antibody. In this instance, it may be preferred thatCDR3 be predicted from an anti-TNF antibody. Particularly however, if more than one CDR is present in the TNF inhibitor, it is preferred that the CDRs are predicted from anti-TNF antibodies. A combination of CDRs may be used from different antibodies, particularly from antibodies that bind to the same desired region or epitope.In a preferred embodiment, the TNF inhibitor comprises three CDRs predicted from thevariable heavy chain sequence of an anti-TNF antibody and / or three CDRs predicted from thevariable light chain sequence of an anti-TNF antibody.Examples of antibodies, and fragments and / or derivatives thereof that can be used in theinvention are further described below. The TNF inhibitor may comprise or consist of an amino acid sequence comprising the CDRs described herein and substitutions, variations,modifications, replacements, deletions and / or additions of one or more amino acid residuesmay occur in the framework region. The derivatives described herein may retain TNF-bindingability. The derivatives may be capable of binding TNF to at least 10%, at least 20%, at least30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or100% of the level of the corresponding reference amino acid sequence.TNF-binding affinity may be determined by equilibrium binding constants (KD), which may bedetermined by any suitable assay e.g. surface plasmon resonance (see e.g. Shealy, D.J., etal., 2010. mAbs, 2(4), pp.428-439). Suitably, an anti-TNF antibody or a fragment thereof maybind to soluble TNF with a binding affinity of about 1000 pM or less, about 900 pM or less,about 800 pM or less, about 700 pM or less, about 600 pM or less, about 500 pM or less,about 400 pM or less, about 300 pM or less, about 200 pM or less, or about 100 pM or less,for example as determined by surface plasmon resonance. Suitably, an anti-TNF antibody ora fragment thereof may bind to soluble TNF with a binding affinity of from about 0.1 pM toabout 1000 pM, from about 1 pM to about 1000 pM, from about 10 pM to about 1000 pM, 0.1pM to about 100 pM, from about 1 pM to about 100 pM, or from about 10 pM to about 100 pM,for example as determined by surface plasmon resonance. Suitably, an anti-TNF antibody ora fragment thereof may bind to transmembrane TNF with a binding affinity of about 10000 pMor less, about 9000 pM or less, about 8000 pM or less, about 7000 pM or less, about 6000 pMor less, about 5000 pM or less, or about 4000 pM or less, for example as determined bysurface plasmon resonance.In some embodiments, the TNF inhibitor is selected from any of: adalimumab, or a fragmentand / or derivative thereof; infliximab, or a fragment and / or derivative thereof; golimumab, or afragment and / or derivative thereof; and certolizumab or a fragment and / or derivative thereof.In some embodiments, the TNF inhibitor is selected from: adalimumab, or a fragment and / orderivative thereof; and infliximab, or a fragment and / or derivative thereof.In some embodiments, the TNF inhibitor is selected from any of: an adalimumab fragment orderivative thereof; an infliximab fragment or derivative thereof; a golimumab fragment orderivative thereof; and a certolizumab fragment or derivative thereof.In some embodiments, the TNF inhibitor is selected from any of: an adalimumab fragment orderivative thereof; and an infliximab fragment or derivative thereof. Adalimumab In preferred embodiments, the TNF inhibitor is adalimumab, or a fragment and / or derivativethereof. In some embodiments, the TNF inhibitor is an adalimumab Fab, an adalimumabF(ab’)2, an adalimumab scFv, an adalimumab sdAb, or a derivative thereof. In someembodiments, the TNF inhibitor is an adalimumab Fab, or a derivative thereof.Adalimumab (Humira®) is a recombinant, fully human IgG1 monoclonal antibody that bindsspecifically to TNF, thereby neutralizing the activity of the cytokine. The skilled person wouldbe able to generate adalimumab derivatives using conservative mutations and / or knowledgeof the mechanism of adalimumab inhibition of TNF (see e.g. Hu, S., et al., 2013. Journal ofBiological Chemistry, 288(38), pp.27059-27067). For example, the following adalimumab variants have been shown to have comparable KD values to wild-type adalimumab: L178K, L178N, Q160N, L116N, T118N, A122N, Q179N, L183N, and T199N (see e.g. Reslan, M., et al., 2020. International Journal of Biological Macromolecules, 158, pp.189-196). In some embodiments, the TNF inhibitor is a fragment of adalimumab, or a derivative thereof.In some embodiments, the TNF inhibitor is an adalimumab Fab, an adalimumab F(ab’)2, anadalimumab scFv, or an adalimumab sdAb, or a derivative thereof. In some embodiments, theTNF inhibitor is an adalimumab Fab, or a derivative thereof.Suitable adalimumab Fab derivatives include those described in Yoshikawa, M., et al., 2022.The Journal of Biochemistry, mvac040; and Nakamura, H., et al., 2020. Biological andPharmaceutical Bulletin, 43(3), pp.418-423. Suitably, an adalimumab Fab derivative may beselected from one or more of: H:K137C-L:I117C, H:K137C-L:F209C, H:S138C-L:F116C, H:S140C-L:S114C, and H:V177C-L:Q160C.In some embodiments, the TNF inhibitor is, or is derived from, an anti-TNF antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 16-21, or variants thereof. In other words, in some embodimentsthe TNF inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 16-21, orvariants thereof. In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 16 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 17 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 18 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 19 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 20 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 21 or a variant thereof.In some embodiments, the TNF inhibitor comprises a HCDR2 having an amino acid sequenceof SEQ ID NO: 17 or a variant thereof and / or a LCDR2 having an amino acid sequence ofSEQ ID NO: 20 or a variant thereof. For adalimumab, CDRs L2 and H2 contribute to themajority of the interactions with the antigen (see Hu, S., et al., 2013. Journal of BiologicalChemistry, 288(38), pp.27059-27067). In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 16 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 17 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 18 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 19 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 20 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 21 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 22. In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 23. In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 22, and the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 23.In some embodiments, the TNF inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 22, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 16 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 17 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 18 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 23, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 19 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 20 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 21 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 24 or 25.In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein thelight chain comprises or consists of an amino acid sequence having at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 26.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 24, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 26.In some embodiments, the TNF inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 24, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 16, a HCDR2 having an amino acid sequence of SEQ ID NO: 17, and a HCDR3 having an amino acid sequence of SEQ ID NO: 18; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 26, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 19, a LCDR2 having an amino acid sequence of SEQ ID NO: 20, and a LCDR3 having an amino acid sequence of SEQ ID NO: 21. Name Example sequenceAdalimumab HCDR1 TFDDYA (SEQ ID NO: 16)Adalimumab HCDR2 TWNSGHID (SEQ ID NO: 17)Adalimumab HCDR3 VSYLSTASSL (SEQ ID NO: 18)Adalimumab LCDR1 GIRNYLA (SEQ ID NO: 19)Adalimumab LCDR2 YAASTLQ (SEQ ID NO: 20)Adalimumab LCDR3 RYNRA (SEQ ID NO: 21)Adalimumab VH EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSAITWNSGHIDYADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVS YLSTASSLDYWGQGTLVTVS (SEQ ID NO: 22)Adalimumab VL DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQRYNRAPYTFGQ GTKVEIK (SEQ ID NO: 23)Adalimumab VH +EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSA CH1 ITWNSGHIDYADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVS YLSTASSLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKV (SEQ ID NO: 24) Adalimumab heavy EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSA chain ITWNSGHIDYADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVS YLSTASSLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG K(SEQ ID NO: 25)Adalimumab light DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLLIYA chain ASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQRYNRAPYTFGQ GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC (SEQ ID NO: 26)Infliximab In some embodiments, the TNF inhibitor is infliximab, or a fragment and / or derivative thereof.In some embodiments, the TNF inhibitor is an infliximab Fab, an infliximab F(ab’)2, aninfliximab scFv, an infliximab sdAb, or a derivative thereof. In some embodiments, the TNFinhibitor is an infliximab Fab, or a derivative thereof.Infliximab (Remicade®) is a chimeric monoclonal antibody to human TNF. It binds to both soluble and transmembrane forms of TNF at picomolar concentrations. The skilled personwould be able to generate infliximab derivatives using conservative mutations and / orknowledge of the mechanism of infliximab inhibition of TNF (see e.g. Liang, S., et al., 2013.Journal of Biological Chemistry, 288(19), pp.13799-13807). In some embodiments, the TNF inhibitor is a fragment of infliximab, or a derivative thereof. In some embodiments, the TNF inhibitor is an infliximab Fab, an infliximab F(ab’)2, an infliximabscFv, or an infliximab sdAb, or a derivative thereof. In some embodiments, the TNF inhibitoris an infliximab Fab, or a derivative thereof.In some embodiments, the TNF inhibitor is, or is derived from, an anti-TNF antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 27-32, or variants thereof. In other words, in some embodimentsthe TNF inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 27-32, orvariants thereof. In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 27 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 28 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 29 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 30 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 31 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 32 or a variant thereof.In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 27 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 28 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 29 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 30 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 31 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 32 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 33. In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 34. In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 33, and the light chaincomprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 34.In some embodiments, the TNF inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 33, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 27 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 28 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 29 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 34, whereinthe amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 30 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 31 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 32 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 35 or 36.In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein thelight chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 37.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 35, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 37.In some embodiments, the TNF inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 35, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 27, a HCDR2 having an amino acid sequence of SEQ ID NO: 28, and a HCDR3 having an amino acid sequence of SEQ ID NO: 29; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 37, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 30, a LCDR2 having an amino acid sequence of SEQ ID NO: 31, and a LCDR3 having an amino acid sequence of SEQ ID NO: 32. Name Example sequenceInfliximab HCDR1 IFSNHW (SEQ ID NO: 27)Infliximab HCDR2 RSKSINSATH (SEQ ID NO: 28)Infliximab HCDR3 NYYGSTY (SEQ ID NO: 29)Infliximab LCDR1 FVGSSIH (SEQ ID NO: 30)Infliximab LCDR2 KYASESM (SEQ ID NO: 31)Infliximab LCDR3 QSHSW (SEQ ID NO: 32)Infliximab VH EVKLEESGGGLVQPGGSMKLSCVASGFIFSNHWMNWVRQSPEKGLEWVAEIRSKSINSATHYAESVKGRFTISRDDSKSAVYLQMTDLRTEDTGVYYCSR NYYGSTYDYWGQGTTLTVSS (SEQ ID NO: 33)Infliximab VL DILLTQSPAILSVSPGERVSFSCRASQFVGSSIHWYQQRTNGSPRLLIKYASESMSGIPSRFSGSGSGTDFTLSINTVESEDIADYYCQQSHSWPFTFGS GTNLEVK (SEQ ID NO: 34)Infliximab VH + CH1 EVKLEESGGGLVQPGGSMKLSCVASGFIFSNHWMNWVRQSPEKGLEWVAEIRSKSINSATHYAESVKGRFTISRDDSKSAVYLQMTDLRTEDTGVYYCSR NYYGSTYDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKV (SEQ ID NO: 35)Infliximab heavy EVKLEESGGGLVQPGGSMKLSCVASGFIFSNHWMNWVRQSPEKGLEWVAE chain IRSKSINSATHYAESVKGRFTISRDDSKSAVYLQMTDLRTEDTGVYYCSR NYYGSTYDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 36) Infliximab light chain DILLTQSPAILSVSPGERVSFSCRASQFVGSSIHWYQQRTNGSPRLLIKYASESMSGIPSRFSGSGSGTDFTLSINTVESEDIADYYCQQSHSWPFTFGS GTNLEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC (SEQ ID NO: 37)Golimumab In some embodiments, the TNF inhibitor is golimumab, or a fragment and / or derivative thereof.In some embodiments, the TNF inhibitor is a golimumab Fab, a golimumab F(ab’)2, agolimumab scFv, a golimumab sdAb, or a derivative thereof. In some embodiments, the TNFinhibitor is a golimumab Fab, or a derivative thereof.Golimumab (Simponi®) is a human IgG1 TNF antagonist monoclonal antibody. The skilledperson would be able to generate golimumab derivatives using conservative mutations and / orknowledge of the mechanism of golimumab inhibition of TNF (see e.g. Shealy, D.J., et al.,2010. MAbs, 2(4), pp.428-439). In some embodiments, the TNF inhibitor is a fragment of golimumab, or a derivative thereof.In some embodiments, the TNF inhibitor is a golimumab Fab, a golimumab F(ab’)2, agolimumab scFv, or a golimumab sdAb, or a derivative thereof. In some embodiments, theTNF inhibitor is a golimumab Fab, or a derivative thereof.In some embodiments, the TNF inhibitor is, or is derived from an anti-TNF antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 38-43, or variants thereof. In other words, in some embodimentsthe TNF inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 38-43, orvariants thereof. In some embodiments, the TNF inhibitor comprises:(i) a HCDR1 having an amino acid sequence of SEQ ID NO: 38 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 39 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 40 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 41 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 42 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 43 or a variant thereof.In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 38 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 39 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 40 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 41 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 42 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 43 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 44. In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 45. In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises an amino acid sequence having at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 44, and the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 45.In some embodiments, the TNF inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 44, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 38 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 39 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 40 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 45, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 41 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 42 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 43 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 46 or 47.In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 48.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%,at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 46, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 48.In some embodiments, the TNF inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 46, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 38, a HCDR2 having an amino acid sequence of SEQ ID NO: 39, and a HCDR3 having an amino acid sequence of SEQ ID NO: 40; and / or(ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 48, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 41, a LCDR2 having an amino acid sequence of SEQ ID NO: 42, and a LCDR3 having an amino acid sequence of SEQ ID NO: 43. Name Example sequenceGolimumab HCDR1 IFSSYA (SEQ ID NO: 38)Golimumab HCDR2 SYDGSNKK (SEQ ID NO: 39)Golimumab HCDR3 NYYYYGM (SEQ ID NO: 40)Golimumab LCDR1 SVYSYLA (SEQ ID NO: 41)Golimumab LCDR2 YDASNRA (SEQ ID NO: 42)Golimumab LCDR3 QRSNW (SEQ ID NO: 43)Golimumab VH QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYAMHWVRQAPGNGLEWVAFMSYDGSNKKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDR GIAAGGNYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 44)Golimumab VL EIVLTQSPATLSLSPGERATLSCRASQSVYSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPFTFG PGTKVDIK (SEQ ID NO: 45) Golimumab VH +QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYAMHWVRQAPGNGLEWVAF CH1 MSYDGSNKKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDR GIAAGGNYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAA LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQTYICNVNHKPSNTKVDKKV (SEQ ID NO: 46) Golimumab heavy QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYAMHWVRQAPGNGLEWVAF chain MSYDGSNKKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDR GIAAGGNYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAA LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG QPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK (SEQ ID NO: 47)Golimumab light EIVLTQSPATLSLSPGERATLSCRASQSVYSYLAWYQQKPGQAPRLLIYD chain ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPFTFG PGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLLLECINENNFYPR EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY ACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 48)Certolizumab In some embodiments, the TNF inhibitor is certolizumab, or a fragment and / or derivativethereof. In some embodiments, the TNF inhibitor is a certolizumab Fab, a certolizumab F(ab’)2,a certolizumab scFv, a certolizumab sdAb, or a derivative thereof. In some embodiments, theTNF inhibitor is a certolizumab Fab, or a derivative thereof.Certolizumab is a humanized antigen-binding fragment (Fab') of a monoclonal antibody, thatis usually administered in a form that is conjugated to polyethylene glycol (Cimzia®). Theskilled person would be able to generate certolizumab derivatives using conservativemutations and / or knowledge of the mechanism of certolizumab inhibition of TNF (see e.g. Lee,J.U., et al., 2017. International journal of molecular sciences, 18(1), p.228).In some embodiments, the TNF inhibitor is a fragment of certolizumab, or a derivative thereof.In some embodiments, the TNF inhibitor is a certolizumab Fab, a certolizumab F(ab’)2, acertolizumab scFv, or a certolizumab sdAb, or a derivative thereof. In some embodiments, theTNF inhibitor is a certolizumab Fab, or a derivative thereof. In some embodiments, the TNF inhibitor is, or is derived from an anti-TNF antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 49-54, or variants thereof. In other words, in some embodimentsthe TNF inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 49-54, orvariants thereof. In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 49 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 50 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 51 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 52 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 53 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 54 or a variant thereof.In some embodiments, the TNF inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 49 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 50 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 51 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 52 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 53 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 54 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 55. In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 56. In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises an amino acid sequence having at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 55, and the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 56.In some embodiments, the TNF inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 55, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 49 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 50 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 51 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 56, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 52 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 53 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 54 or a variant thereof.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 57 or 58.In some embodiments, the TNF inhibitor comprises or consists of a light chain, wherein the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 59.In some embodiments, the TNF inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%,at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 57, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 59.In some embodiments, the TNF inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 57, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 49, a HCDR2 having an amino acid sequence of SEQ IDNO: 50, and a HCDR3 having an amino acid sequence of SEQ ID NO: 51; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 59, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 49, a LCDR2 having an amino acid sequence of SEQ ID NO: 50, and a LCDR3 having an amino acid sequence of SEQ ID NO: 51. Name Example sequenceCertolizumab HCDR1 VFTDYG (SEQ ID NO: 49)Certolizumab HCDR2 NTYIGEPI (SEQ ID NO: 50)Certolizumab HCDR3 GYRSYAM (SEQ ID NO: 51)Certolizumab LCDR1 NVGTNVA (SEQ ID NO: 52)Certolizumab LCDR2 YSASFLY (SEQ ID NO: 53)Certolizumab LCDR3 QYNIY (SEQ ID NO: 54)Certolizumab VH EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGWINTYIGEPIYADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGY RSYAMDYWGQGTLVTVSS (SEQ ID NO: 55)Certolizumab VL DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASFLYSGVPYRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPLTFGQ GTKVEIK (SEQ ID NO: 56)Certolizumab VH +EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGW CH1 INTYIGEPIYADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGY RSYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKV (SEQ ID NO: 57)Certolizumab heavy EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGW chain INTYIGEPIYADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGY RSYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSCDKTHTCAA (SEQ ID NO: 58) Certolizumab light DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYS chain ASFLYSGVPYRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPLTFGQ GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC (SEQ ID NO: 59)Other TNF inhibitors In some embodiments, the TNF inhibitor comprises the TNF-binding domain of a TNF receptor (TNFR). TNF signals through two receptors (TNFR1 and TNFR2) that share a similar structural arrangement with an N-terminal extracellular domain (ECD) composed of four cysteine-rich domains (CRDs), an α-helical transmembrane domain and a cytoplasmic domain. The two receptors are most divergent in the cytoplasmic domain, where TNFR1 has a death domainthat is absent from TNFR2 (see e.g. Bodmer, J.L., et al. Trends in biochemical sciences, 27(1),pp.19-26) In some embodiments, the TNF inhibitor comprises a soluble form of a TNF receptor (TNFR). In some embodiments, the TNF inhibitor comprises a soluble form of TNFR1 or TNFR2. In some embodiments, the TNF inhibitor comprises or consists a soluble form of TNFR2.The TNF-binding domain and / or soluble form of a TNF receptor may be fused to any suitabledomain. Suitably, the TNF-binding domain and / or soluble form of a TNF receptor may becoupled to an Fc domain (e.g. the Fc portion of human IgG1).Etanercept In some embodiments, the TNF inhibitor is etanercept or a derivative thereof. Etanercept (Enbrel®) is a fusion protein, consisting of a TNFR2 domain coupled to the Fcportion of human IgG1. The skilled person would be able to generate etanercept derivativesusing conservative mutations and / or knowledge of the mechanism of etanercept inhibition ofTNF (see e.g. Lamanna, W.C., et al., 2017. Scientific reports, 7(1), pp.1-8).In some embodiments, the TNF inhibitor comprises or consists of an amino acid sequencehaving at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 60. In some embodiments, the TNF inhibitor comprises or consists of the amino acid sequence of SEQ ID NO: 60. LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDSTYT QLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRKCRPG FGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTSTSPTRS MAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Example etanercept sequence (SEQ ID NO: 60)Other fusion proteins In some embodiments, the TNF inhibitor is a fusion protein, consisting of a TNFR1 extracellular domain coupled to the Fc portion of human IgG1. In some embodiments, the TNF inhibitor comprises or consists of an amino acid sequencehaving at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 61. In some embodiments, the TNF inhibitor comprises or consists of the amino acid sequence of SEQ ID NO: 61. MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTKC HKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDRDTV CGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVSCSNCK KSLECTKLCLPQIENVKGTEDSGTTDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK Example fusion protein sequence (SEQ ID NO: 61)TNF-specific aptamers Other suitable TNF inhibitors include TNF-specific DNA aptamers, and TNF-specific RNA aptamers (see e.g. Lai, W.Y., et al., 2019. Theranostics, 9(6), p.1741; and Yan, X., et al., 2004. Genomics, Proteomics & Bioinformatics, 2(1), pp.32-42.).Aptamers are single-stranded DNA- or RNA-based synthetic oligonucleotides, which adoptcomplex three-dimensional conformations that allow them to bind and interact with a wide variety of targets with high affinity and specificity.In some embodiments, the TNF inhibitor is a TNF-specific aptamer. In some embodiments,the TNF inhibitor is a TNF-specific DNA aptamer. In some embodiments, the TNF inhibitor isa TNF-specific RNA aptamer. Example nucleotide sequencesThe TNF inhibitor may be encoded by any suitable nucleotide sequence. In someembodiments, the nucleotide sequence is codon-optimised, for example codon-optimised forexpression in humans. Suitably, a nucleotide sequence encoding an anti-TNF Fab may comprise from 5’ to 3’: a firstsignal sequence; a nucleotide encoding a heavy chain (e.g. VH + CH1); a linker sequence; asecond signal sequence; and a nucleotide encoding a light chain. Suitably, a nucleotide sequence encoding an anti-TNF Fab may comprise from 5’ to 3’: a first signal sequence; a nucleotide encoding a light chain; a linker sequence; a second signal sequence; and anucleotide encoding a heavy chain (e.g. VH + CH1).Heavy chains and light chainsThe nucleotide encoding a heavy chain (e.g. VH + CH1) and the nucleotide encoding a lightchain may encode any heavy chain (e.g. VH + CH1) and light chain combination describedherein. For example, the nucleotide sequence encoding an anti-TNF Fab may comprise from5’ to 3’: (a) a first signal sequence; a nucleotide encoding an adalimumab heavy chain (e.g.VH + CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an adalimumab light chain, or a derivative thereof; (b) a first signal sequence; a nucleotide encoding an infliximab heavy chain (e.g. VH +CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an infliximab light chain, or a derivative thereof; (c) a first signal sequence; a nucleotide encoding a golimumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a golimumab light chain, or a derivative thereof; (d) a first signal sequence; a nucleotide encoding a certolizumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and anucleotide encoding a certolizumab light chain, or a derivative thereof; (e) a first signal sequence; a nucleotide encoding an adalimumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an adalimumab heavy chain (e.g. VH + CH1), or a derivative thereof; (f) a first signal sequence; a nucleotide encoding an infliximab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an infliximab heavy chain (e.g. VH + CH1), or a derivative thereof;(g) a first signal sequence; a nucleotide encoding a golimumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a golimumab heavy chain (e.g. VH + CH1), or a derivative thereof; or(h) a first signal sequence; a nucleotide encoding a certolizumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a certolizumab heavy chain (e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding an anti-TNF Fab may comprisefrom 5’ to 3’: a first signal sequence; a nucleotide encoding an adalimumab heavy chain (e.g.VH + CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an adalimumab light chain, or a derivative thereof. In some embodiments,the nucleotide sequence encoding an anti-TNF Fab may comprise from 5’ to 3’: a first signalsequence; a nucleotide encoding an adalimumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an adalimumab heavy chain (e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding an adalimumab heavy chain (e.g.VH + CH1) comprises or consists of a nucleotide sequence having at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 62. In some embodiments, thenucleotide sequence encoding an adalimumab heavy chain (e.g. VH + CH1) comprises orconsists of SEQ ID NO: 62. gaggtgcaactggtggaaagcggcggcggcctggtccagcctggaaggtccctgagactgag ctgtgccgccagcggctttaccttcgacgactacgccatgcactgggtgcgccaggcccctg gcaagggcctggaatgggtctccgccatcacctggaatagcggccacatcgactacgccgat agcgtggaaggcagattcaccatcagccgggacaacgccaagaactctctgtatctgcaaat gaacagcctgcgggctgaagatacagccgtgtactattgcgccaaagtgagctacctctcca ccgccagcagcctggactattggggacagggcaccctggtgaccgtgtctagcgcctccaca aagggcccttctgtgtttccactggctccaagctccaaaagcacatctggaggaaccgctgc cctgggctgcctggttaaggactacttccccgagcctgtgaccgtgagctggaacagcggcg ccctgacatctggtgttcataccttccctgccgttctgcaatcttctggactctacagcctg tcttctgtggtgaccgtgcccagcagcagccttggaacacagacctacatctgcaatgtgaa ccacaagcctagcaacaccaaggtggacaagaaggtg Example nucleotide sequence encoding an adalimumab heavy chain (VH + CH1) (SEQ ID NO: 62)In some embodiments, the nucleotide sequence encoding an adalimumab light chaincomprises or consists of a nucleotide sequence having at least 70%, at least 75%, at least80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 63. In some embodiments, nucleotidesequence encoding an adalimumab light chain comprises or consists of SEQ ID NO: 63.gacatccagatgacccagagcccttcctcactgagcgccagcgtgggcgacagagtgactat tacatgcagagccagccaaggcatccggaactacctggcctggtatcagcagaagcccggca aagcccctaagctgctgatctacgccgccagcaccctgcaaagcggcgtgcctagcagattc agcggctcaggctctggcactgatttcaccctgaccatctcctctctgcaacctgaggacgt ggccacatactactgccagagatacaacagagccccatacacctttggccagggcacaaaag tggaaatcaagagaaccgtggccgctcccagtgtgttcatcttcccccccagtgatgagcag ctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctaccccagagaggccaa ggtgcagtggaaggtggataatgccctgcaaagcggcaacagccaggagagcgtgacagagc aggacagcaaggacagcacctacagcctctctagcacactgaccctgagcaaggccgactac gagaagcacaaggtgtacgcatgcgaggtgacccaccagggcctgagcagtcctgtgaccaa gagcttcaaccggggcgagtgt Example nucleotide sequence encoding an adalimumab light chain (SEQ ID NO: 63)In some embodiments, the nucleotide sequence encoding an anti-TNF Fab may comprisefrom 5’ to 3’: a first signal sequence; a nucleotide encoding an infliximab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an infliximab light chain, or a derivative thereof. In some embodiments, thenucleotide sequence encoding an anti-TNF Fab may comprise from 5’ to 3’: a first signalsequence; a nucleotide encoding an infliximab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an infliximab heavy chain (e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding an infliximab heavy chain (e.g. VH+ CH1) comprises or consists of a nucleotide sequence having at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 64. In some embodiments, nucleotidesequence encoding an infliximab heavy chain (e.g. VH + CH1) comprises or consists of SEQID NO: 64. gaggtgaaactggaggaaagtggaggaggcctcgttcaaccaggcggctccatgaagctgtc gtgtgtggcatctggcttcatcttcagcaatcactggatgaactgggtcaggcaatctcctg agaaggggctagagtgggtggcggagatccgctcaaaatcaatcaattccgccacacattat gcagagtcagtaaaagggcggttcaccatttctagagatgacagcaaaagcgccgtgtacct ccagatgaccgacctgcgaacagaggacactggggtctactactgctcccggaactactatg gctccacctatgactactggggccaagggaccacattgacagtatcctcagcctccactaaa ggtccttcagtgtttccgctggctccctcctccaaaagtacgtcaggcggcaccgctgctct gggctgtctggtgaaggattacttccctgaacctgtgactgtttcctggaacagtggagcct tgacttcaggagtccacacatttccggcagtgctccagagcagtggtctctattccctaagc agtgtagtgaccgtgccctctagcagcctcggaacccagacatacatctgcaatgtcaatca caagccaagcaatacaaaagtggacaagaaggtt Example nucleotide sequence encoding an infliximab heavy chain (VH + CH1) (SEQ ID NO: 64)In some embodiments, the nucleotide sequence encoding an infliximab light chain comprisesor consists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 65. In some embodiments, nucleotide sequence encoding aninfliximab light chain comprises or consists of SEQ ID NO: 65. gacattctcctgacccagtcccctgctatcttgtctgtctcccccggagagcgcgtctcctt ctcttgcagagcttcccagtttgtgggcagcagcattcactggtatcagcagagaacaaatg gatcaccaaggcttttgatcaagtatgcttcagaaagcatgagtgggataccatccaggttt agtggaagtggctctggtactgacttcactctctctataaacacggtggaaagcgaagatat tgctgactattactgtcagcaaagccatagctggccatttacttttggatcagggaccaacc tggaagtcaagagaactgtggccgcgccttcggtttttattttccccccatctgatgaacag ctgaagagcggtacagccagtgtagtgtgcctgctcaacaacttctaccctagagaagccaa ggtgcagtggaaggtcgacaatgcattacagagcgggaacagccaggaaagtgttactgagc aggatagcaaggacagcacctactctctgtctagcacactcactttgtctaaagcagattat gagaaacataaagtttatgcctgtgaagttacccaccagggcctgagcagtcccgtcaccaa gtctttcaaccgcggggagtgc Example nucleotide sequence encoding an infliximab light chain (SEQ ID NO: 65)Example anti-TNF Fab sequencesIn some embodiments, the nucleotide sequence encoding an anti-TNF Fab encodes an aminoacid sequence comprising or consisting of from 5’ to 3’: an amino acid sequence having atleast 70% identity to SEQ ID NO: 1, an amino acid sequence having at least 70% identity to SEQ ID NO: 22, an amino acid sequence having at least 70% sequence identity to any of SEQ ID NOs: 6-9, an amino acid sequence having at least 70% identity to SEQ ID NO: 1, and anamino acid sequence having at least 70% identity to SEQ ID NO: 23.In some embodiments, the nucleotide sequence encoding an anti-TNF Fab encodes an aminoacid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity toSEQ ID NO: 66. In some embodiments, the nucleotide sequence encoding an anti-TNF Fabencodes the amino acid sequence of SEQ ID NO: 66. MATGSRTSLLLAFGLLCLPWLQEGSAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHW VRQAPGKGLEWVSAITWNSGHIDYADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAK VSYLSTASSLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVRKR RSGSGATNFSLLKQAGDVEENPGPMATGSRTSLLLAFGLLCLPWLQEGSADIQMTQSPSSLS ASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLT ISSLQPEDVATYYCQRYNRAPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC Example adalimumab Fab amino acid sequence (SEQ ID NO: 66)In some embodiments, the nucleotide sequence encoding an anti-TNF Fab comprises orconsists of from 5’ to 3’: a nucleotide sequence having at least 70% identity to any of SEQ IDNOs: 2-5, a nucleotide sequence having at least 70% identity to SEQ ID NO: 62, a nucleotidesequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, a nucleotidesequence having at least 70% identity to any of SEQ ID NOs: 2-5, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 63.In some embodiments, the nucleotide sequence encoding an anti-TNF Fab comprises orconsists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 67. In some embodiments, the nucleotide sequence encodingan anti-TNF Fab comprises or consists of SEQ ID NO: 67.atggccacaggctctcggaccagcctgctgctggccttcggcctgctgtgtctgccttggct gcaagagggcagcgccgaggtgcaactggtggaaagcggcggcggcctggtccagcctggaa ggtccctgagactgagctgtgccgccagcggctttaccttcgacgactacgccatgcactgg gtgcgccaggcccctggcaagggcctggaatgggtctccgccatcacctggaatagcggcca catcgactacgccgatagcgtggaaggcagattcaccatcagccgggacaacgccaagaact ctctgtatctgcaaatgaacagcctgcgggctgaagatacagccgtgtactattgcgccaaa gtgagctacctctccaccgccagcagcctggactattggggacagggcaccctggtgaccgt gtctagcgcctccacaaagggcccttctgtgtttccactggctccaagctccaaaagcacat ctggaggaaccgctgccctgggctgcctggttaaggactacttccccgagcctgtgaccgtg agctggaacagcggcgccctgacatctggtgttcataccttccctgccgttctgcaatcttc tggactctacagcctgtcttctgtggtgaccgtgcccagcagcagccttggaacacagacct acatctgcaatgtgaaccacaagcctagcaacaccaaggtggacaagaaggtgagaaagcgg agaagcggaagcggtgctaccaacttcagcctcctgaaacaggccggcgatgtggaggaaaa ccctggacctatggctaccggcagcagaaccagcctgctgctggcattcggccttctgtgcc tgccttggctgcaagagggctctgccgacatccagatgacccagagcccttcctcactgagc gccagcgtgggcgacagagtgactattacatgcagagccagccaaggcatccggaactacct ggcctggtatcagcagaagcccggcaaagcccctaagctgctgatctacgccgccagcaccc tgcaaagcggcgtgcctagcagattcagcggctcaggctctggcactgatttcaccctgacc atctcctctctgcaacctgaggacgtggccacatactactgccagagatacaacagagcccc atacacctttggccagggcacaaaagtggaaatcaagagaaccgtggccgctcccagtgtgt tcatcttcccccccagtgatgagcagctgaagtccggcacagcctctgtcgtgtgcctgctg aacaacttctaccccagagaggccaaggtgcagtggaaggtggataatgccctgcaaagcgg caacagccaggagagcgtgacagagcaggacagcaaggacagcacctacagcctctctagca cactgaccctgagcaaggccgactacgagaagcacaaggtgtacgcatgcgaggtgacccac cagggcctgagcagtcctgtgaccaagagcttcaaccggggcgagtgt Example adalimumab Fab nucleotide sequence (SEQ ID NO: 67)In some embodiments, the nucleotide sequence encoding an anti-TNF Fab encodes an aminoacid sequence comprising or consisting of from 5’ to 3’: an amino acid sequence having at least 70% identity to SEQ ID NO: 1, an amino acid sequence having at least 70% identity to SEQ ID NO: 33, an amino acid sequence having at least 70% sequence identity to any of SEQ ID NOs: 6-9, an amino acid sequence having at least 70% identity to SEQ ID NO: 1, and anamino acid sequence having at least 70% identity to SEQ ID NO: 34.In some embodiments, the nucleotide sequence encoding an anti-TNF Fab encodes an aminoacid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity toSEQ ID NO: 68. In some embodiments, the nucleotide sequence encoding an anti-TNF Fabencodes the amino acid sequence of SEQ ID NO: 68. MATGSRTSLLLAFGLLCLPWLQEGSAEVKLEESGGGLVQPGGSMKLSCVASGFIFSNHWMNW VRQSPEKGLEWVAEIRSKSINSATHYAESVKGRFTISRDDSKSAVYLQMTDLRTEDTGVYYC SRNYYGSTYDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVRKRR SGSGATNFSLLKQAGDVEENPGPMATGSRTSLLLAFGLLCLPWLQEGSADILLTQSPAILSV SPGERVSFSCRASQFVGSSIHWYQQRTNGSPRLLIKYASESMSGIPSRFSGSGSGTDFTLSI NTVESEDIADYYCQQSHSWPFTFGSGTNLEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC Example infliximab Fab amino acid sequence (SEQ ID NO: 68)In some embodiments, the nucleotide sequence encoding an anti-TNF Fab comprises orconsists of from 5’ to 3’: a nucleotide sequence having at least 70% identity to any of SEQ IDNOs: 2-5, a nucleotide sequence having at least 70% identity to SEQ ID NO: 64, a nucleotidesequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, a nucleotidesequence having at least 70% identity to any of SEQ ID NOs: 2-5, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 65.In some embodiments, the nucleotide sequence encoding an anti-TNF Fab comprises orconsists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 69. In some embodiments, the nucleotide sequence encodingan anti-TNF Fab comprises or consists of SEQ ID NO: 69.atggcaacaggtagtcgaaccagcctattactggccttcggtctcctgtgtctgccctggct tcaagagggctctgctgaggtgaaactggaggaaagtggaggaggcctcgttcaaccaggcg gctccatgaagctgtcgtgtgtggcatctggcttcatcttcagcaatcactggatgaactgg gtcaggcaatctcctgagaaggggctagagtgggtggcggagatccgctcaaaatcaatcaa ttccgccacacattatgcagagtcagtaaaagggcggttcaccatttctagagatgacagca aaagcgccgtgtacctccagatgaccgacctgcgaacagaggacactggggtctactactgc tcccggaactactatggctccacctatgactactggggccaagggaccacattgacagtatc ctcagcctccactaaaggtccttcagtgtttccgctggctccctcctccaaaagtacgtcag gcggcaccgctgctctgggctgtctggtgaaggattacttccctgaacctgtgactgtttcc tggaacagtggagccttgacttcaggagtccacacatttccggcagtgctccagagcagtgg tctctattccctaagcagtgtagtgaccgtgccctctagcagcctcggaacccagacataca tctgcaatgtcaatcacaagccaagcaatacaaaagtggacaagaaggttaggaagcggcgt tccgggagcggggctacgaatttttcattgctcaagcaagcgggagatgtggaggagaaccc tggccccatggccacgggaagtcggacttccttactactcgcctttggtcttctttgcttgc catggctccaggagggtagtgcagacattctcctgacccagtcccctgctatcttgtctgtc tcccccggagagcgcgtctccttctcttgcagagcttcccagtttgtgggcagcagcattca ctggtatcagcagagaacaaatggatcaccaaggcttttgatcaagtatgcttcagaaagca tgagtgggataccatccaggtttagtggaagtggctctggtactgacttcactctctctata aacacggtggaaagcgaagatattgctgactattactgtcagcaaagccatagctggccatt tacttttggatcagggaccaacctggaagtcaagagaactgtggccgcgccttcggttttta ttttccccccatctgatgaacagctgaagagcggtacagccagtgtagtgtgcctgctcaac aacttctaccctagagaagccaaggtgcagtggaaggtcgacaatgcattacagagcgggaa cagccaggaaagtgttactgagcaggatagcaaggacagcacctactctctgtctagcacac tcactttgtctaaagcagattatgagaaacataaagtttatgcctgtgaagttacccaccag ggcctgagcagtcccgtcaccaagtctttcaaccgcggggagtgc Example infliximab Fab nucleotide sequence (SEQ ID NO: 69)CD3 inhibitors The combination of the present invention comprises a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same. The present invention also provides CD3 inhibitors, and polynucleotides and vectors comprising a nucleotide sequence encoding the same. The present inventors havesurprisingly shown that intraocular administration of a CD3 inhibitor, or a polynucleotide orvector comprising a nucleotide sequence encoding the same, may be used to prevent or treat an inflammatory eye disease.As used herein, a “CD3 inhibitor” may refer to any protein or oligonucleotide that suppressesT-cell activation by interacting with the T-cell receptor (TCR)-CD3 complex. CD3 (cluster ofdifferentiation 3) is a protein complex and T cell co-receptor. In mammals, the CD3 complexcontains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with theT-cell receptor (TCR) and the CD3ζ chain to generate an activation signal in T lymphocytes(see e.g. Kuhns, M.S. et al., 2006. Deconstructing the form and function of the TCR / CD3 complex. Immunity, 24(2), pp.133-139).Example CD3 inhibitors include foralumab, teplizumab, visilizumab, otelixizumab,muromonab-CD3, T3 / 4.A, YTH12.5, HuM291, 145-2C11, G4.18, 17A2, Dow2, 20-2b2,blinatumomab, tebentafusp, CD3-specific DNA aptamers, and CD3-specific RNA aptamers(see e.g. Kuhn, C. and Weiner, H.L., 2016. Immunotherapy, 8(8), pp.889-906; Sugita, S., et al., 2017. Arthritis Research & Therapy, 19, pp.1-12; Menon, A.P., et al., 2023. Cancers, 15(4),p.1189; and Renders, L. and Valerius, T., 2003. Clinical & Experimental Immunology, 133(3),pp.307-309). In preferred embodiments, the CD3 inhibitor is a human-specific CD3 inhibitor, i.e. a proteinor oligonucleotide that suppresses T-cell activation by binding to human CD3. In someembodiments, the CD3 inhibitor is an anti-human CD3 antibody or a fragment thereof (e.g.foralumab, teplizumab, visilizumab, otelixizumab, muromonab-CD3, T3 / 4.A, YTH12.5,HuM291, or fragments thereof). Suitably, a CD3 inhibitor may suppress T-cell activation by binding to a CD3γ chain, a CD3δ chain, and / or a CD3ε chain. In some embodiments, a CD3 inhibitor may inhibit CD3 activity by binding to a CD3ε chain. For example, a CD3 inhibitor may be an anti-CD3ε antibody (e.g. foralumab, teplizumab, visilizumab, otelixizumab, or muromonab-CD3) or a fragment thereof. In some embodiments, the CD3 inhibitor is an anti-human CD3ε antibody or a fragment thereof(e.g. foralumab, teplizumab, visilizumab, otelixizumab, and muromonab-CD3, or fragmentsthereof).Anti-CD3 antibody or fragment thereofIn some embodiments, the CD3 inhibitor comprises or consists of an anti-CD3 antibody or a fragment thereof. In preferred embodiments, the CD3 inhibitor is an anti-CD3 antibody or a fragment thereof.The anti-CD3 antibody may be a monoclonal antibody (mAb) or a fragment thereof. In someembodiments, the CD3 inhibitor is a humanized anti-CD3 mAb or a fragment thereof. In someembodiments, the CD3 inhibitor is a human anti-CD3 mAb or a fragment thereof.Suitable anti-CD3 antibodies are known in the art. Moreover, anti-CD3 antibodies, andfragments and / or derivatives thereof, can be prepared using methods known by those of skillin the art. Such methods include phage display, methods to generate human or humanized antibodies, or methods using transgenic animal or plant engineered to produce human antibodies. Phage display libraries of partially or fully synthetic antibodies are available and can be screened for an antibody or fragment thereof that can bind to the target molecule.Phage display libraries of human antibodies are also available. Once identified, the amino acidsequence or polynucleotide sequence encoding for the antibody (or fragment and / or derivative thereof) can be isolated and / or determined. The sequence of the antibody can be used to design suitable fragments and / or derivatives thereof. In preferred embodiments, the anti-CD3 antibody or fragment thereof is an anti-CD3 antibodyfragment. An “anti-CD3 antibody fragment” may be a fragment of an anti-CD3 antibody, or agenetically engineered product of one of more fragments of the anti-CD3 antibody, whichfragment is involved in binding with CD3. In some embodiments, the anti-CD3 antibody fragment is an antigen-binding fragment (Fab), a fragment antibody (F(ab’)2), a single chain antibody (scFv), or a single-domain antibody (sdAb). In preferred embodiments, the anti-CD3 antibody fragment is an antigen-binding fragment (Fab).The CD3 inhibitor may comprise at least one CDR (e.g. HCDR3), which can be predicted froman anti-CD3 antibody (or a variant of such a predicted CDR e.g. a variant with one, two orthree amino acid substitutions). It will be appreciated that molecules containing three or fewerCDR regions (e.g. a single CDR or even a part thereof) may be capable of retaining the antigen-binding activity of the antibody from which the CDR is derived. Molecules containing two CDR regions are described in the art as being capable of binding to a target antigen, e.g.in the form of a minibody (see e.g. Vaughan and Sollazzo, 2001, Combinational Chemistry &High Throughput Screening, 4, 417-430). Molecules containing a single CDR have been described which can display strong binding activity to target (see e.g. Nicaise et al, 2004, Protein Science, 13: 1882-91). The CD3 inhibitor may comprise one or more variable heavy chain CDRs, e.g. one, two or three variable heavy chain CDRs. Alternatively, or additionally, the CD3 inhibitor may comprise one or more variable light chain CDRs, e.g. one, two or three variable light chain CDRs. TheCD3 inhibitor may comprise three heavy chain CDRs and / or three light chain CDRs (and moreparticularly a heavy chain variable region comprising three CDRs and / or a light chain variableregion comprising three CDRs) wherein at least one CDR, preferably all CDRs, may be from an anti-CD3 antibody, or may be selected from one of the CDR sequences provided below.The CD3 inhibitor may comprise any combination of variable heavy and light chain CDRs, e.g.one variable heavy chain CDR together with one variable light chain CDR, two variable heavy chain CDRs together with one variable light chain CDR, two variable heavy chain CDRs together with two variable light chain CDRs, three variable heavy chain CDRs together with one or two variable light chain CDRs, one variable heavy chain CDR together with two or three variable light chain CDRs, or three variable heavy chain CDRs together with three variablelight chain CDRs. Preferably, the CD3 inhibitor comprises three variable heavy chain CDRs(HCDR1, HCDR2 and HCDR3) and / or three variable light chain CDRs (LCDR1, LCDR2 andLCDR3).The one or more CDRs present within the CD3 inhibitor may not all be from the same antibody,as long as the domain has the binding activity described above. Thus, one CDR may be predicted from the heavy or light chains of an anti-CD3 antibody, whilst another CDR presentmay be predicted from a different anti-CD3 antibody. In this instance, it may be preferred thatCDR3 be predicted from an anti-CD3 antibody. Particularly however, if more than one CDR ispresent in the CD3 inhibitor, it is preferred that the CDRs are predicted from anti-CD3antibodies. A combination of CDRs may be used from different antibodies, particularly from antibodies that bind to the same desired region or epitope.In a preferred embodiment, the CD3 inhibitor comprises three CDRs predicted from thevariable heavy chain sequence of an anti-CD3 antibody and / or three CDRs predicted from thevariable light chain sequence of an anti-CD3 antibody.Examples of antibodies, and fragments and / or derivatives thereof that can be used in the invention are further described below. The CD3 inhibitor may comprise or consist of an amino acid sequence comprising the CDRs described herein and substitutions, variations,modifications, replacements, deletions and / or additions of one or more amino acid residuesmay occur in the framework region. The derivatives described herein may retain CD3-bindingability. The derivatives may be capable of binding CD3 to at least 10%, at least 20%, at least30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or100% of the level of the corresponding reference amino acid sequence.CD3-binding affinity may be determined by equilibrium binding constants (KD), which may bedetermined by any suitable assay e.g. surface plasmon resonance (see e.g. Kjer-Nielsen, L.,et al., 2004. PNAS, 101(20), pp.7675-7680). Suitably, an anti-CD3 antibody or a fragment thereof may bind to human CD3 with a binding affinity of about 10 µM or less, 1 µM or less, 100 nM or less, 10 nM or less, 1000 pM or less, about 900 pM or less, about 800 pM or less, about 700 pM or less, about 600 pM or less, about 500 pM or less, about 400 pM or less, about 300 pM or less, about 200 pM or less, or about 100 pM or less, for example as determined by surface plasmon resonance. Suitably, an anti-CD3 antibody or a fragment thereof may bind to human CD3 with a binding affinity of from about 0.1 pM to about 10 µM,from about 0.1 pM to about 1 µM, from about 0.1 pM to about 100 nM, from about 0.1 pM toabout 10 nM, or from about 0.1 pM to about 1000 pM, for example as determined by surface plasmon resonance. Suitably, an anti-CD3 antibody or a fragment thereof may bind to humanCD3 with a binding affinity of from about 1 pM to about 10 µM, from about 1 pM to about 1µM, from about 1 pM to about 100 nM, from about 1 pM to about 10 nM, or from about 1 pM to about 1000 pM, for example as determined by surface plasmon resonance. Suitably, ananti-CD3 antibody or a fragment thereof may bind to human CD3 with a binding affinity of fromabout 10 pM to about 10 µM, from about 10 pM to about 1 µM, from about 10 pM to about 100nM, from about 10 pM to about 10 nM, or from about 10 pM to about 1000 pM, for example asdetermined by surface plasmon resonance. Suitably, an anti-CD3 antibody or a fragmentthereof may bind to human CD3 with a binding affinity of from about 100 pM to about 10 µM,from about 100 pM to about 1 µM, from about 100 pM to about 100 nM, from about 100 pM toabout 10 nM, or from about 100 pM to about 1000 pM, for example as determined by surfaceplasmon resonance.In some embodiments, the CD3 inhibitor is selected from any of: foralumab, or a fragmentand / or derivative thereof; teplizumab, or a fragment and / or derivative thereof; visilizumab, ora fragment and / or derivative thereof; otelixizumab or a fragment and / or derivative thereof; muromonab-CD3, or a fragment and / or derivative thereof; T3 / 4.A or a fragment and / orderivative thereof; YTH12.5, or a fragment and / or derivative thereof; and HuM291, or afragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is selected from any of: foralumab, or a fragmentand / or derivative thereof; teplizumab, or a fragment and / or derivative thereof; visilizumab, ora fragment and / or derivative thereof; otelixizumab or a fragment and / or derivative thereof; and muromonab-CD3 or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is selected from any of: foralumab, or a fragmentand / or derivative thereof; teplizumab, or a fragment and / or derivative thereof; visilizumab, ora fragment and / or derivative thereof; and otelixizumab or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is selected from: foralumab, or a fragment and / orderivative thereof; and teplizumab, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is foralumab, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is selected from any of: a foralumab fragment orderivative thereof; a teplizumab fragment or derivative thereof; a visilizumab fragment orderivative thereof; a otelixizumab fragment or derivative thereof; a muromonab-CD3 fragmentor derivative thereof; a T3 / 4.A fragment or derivative thereof; a YTH12.5 fragment or derivativethereof; and a HuM291 fragment or derivative thereof.In some embodiments, the CD3 inhibitor is selected from any of: a foralumab fragment orderivative thereof; a teplizumab fragment or derivative thereof; a visilizumab fragment orderivative thereof; a otelixizumab fragment or derivative thereof; and a muromonab-CD3 fragment or derivative thereof.In some embodiments, the CD3 inhibitor is selected from any of: a foralumab fragment orderivative thereof; a teplizumab fragment or derivative thereof; a visilizumab fragment orderivative thereof; and a otelixizumab fragment or derivative thereof.In some embodiments, the CD3 inhibitor is selected from any of: a foralumab fragment orderivative thereof; and a teplizumab fragment or derivative thereof.In some embodiments, the CD3 inhibitor is a foralumab fragment or derivative thereof.Foralumab In some embodiments, the CD3 inhibitor is foralumab, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is a foralumab Fab, a foralumab F(ab’)2, a foralumabscFv, a foralumab sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is aforalumab Fab, or a derivative thereof.Foralumab is a fully human IgG1 monoclonal antibody that binds specifically to CD3ε, therebysuppressing T-cell activation. The heavy chain constant regions are mutated at two aminoacid positions, L234A and L235E (see e.g. Ilan, Y., et al., 2018. Clinical & ExperimentalImmunology, 193(3), pp.275-283). The skilled person would be able to generate foralumab derivatives using conservative mutations and / or knowledge of the mechanism of foralumabbinding to CD3.In some embodiments, the CD3 inhibitor is a fragment of foralumab, or a derivative thereof. Insome embodiments, the CD3 inhibitor is a foralumab Fab, a foralumab F(ab’)2, a foralumabscFv, or a foralumab sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is a foralumab Fab, or a derivative thereof. In some embodiments, the CD3 inhibitor is, or is derived from, an anti-CD3 antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 70-75, or variants thereof. In other words, in some embodimentsthe CD3 inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 70-75, orvariants thereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 70 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 71 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 72 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 73 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 74 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 75 or a variant thereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 70 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 71 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 72 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 73 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 74 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 75 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 76. In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 77. In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 76, and the light chaincomprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 77.In some embodiments, the CD3 inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 76, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 70 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 71 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 72 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 77, whereinthe amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQID NO: 73 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 74 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 75 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 78 or 79.In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 80.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 78, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 80.In some embodiments, the CD3 inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ IDNO: 78, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 70, a HCDR2 having an amino acid sequence of SEQ ID NO: 71, and a HCDR3 having an amino acid sequence of SEQ ID NO: 72; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 80, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 73, a LCDR2 having an amino acid sequence of SEQ ID NO: 74, and a LCDR3 having an amino acid sequence of SEQ ID NO: 75. Name Example sequenceForalumab HCDR1 GYGMH (SEQ ID NO: 70)Foralumab HCDR2 VIWYDGSKKYYVDSVKG (SEQ ID NO: 71)Foralumab HCDR3 QMGYWHFDL (SEQ ID NO: 72)Foralumab LCDR1 RASQSVSSYLA (SEQ ID NO: 73)Foralumab LCDR2 DASNRAT (SEQ ID NO: 74)Foralumab LCDR3 QQRSNWPPLT (SEQ ID NO: 75)Foralumab VH QVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQAPGKGLEWVAVIWYDGSKKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQM GYWHFDLWGRGTLVTV (SEQ ID NO: 76)Foralumab VL EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPLTFG GGTKVEIK (SEQ ID NO: 77)Foralumab VH + CH1 QVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQAPGKGLEWVAVIWYDGSKKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQM GYWHFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKRV (SEQ ID NO: 78)Foralumab heavy QVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHWVRQAPGKGLEWVAV chain IWYDGSKKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQM GYWHFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAEGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 79) Foralumab light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPLTFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC (SEQ ID NO: 80)Teplizumab In some embodiments, the CD3 inhibitor is teplizumab, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is a teplizumab Fab, a teplizumab F(ab’)2, ateplizumab scFv, a teplizumab sdAb, or a derivative thereof. In some embodiments, the CD3inhibitor is a teplizumab Fab, or a derivative thereof.Teplizumab is a recombinant, humanized IgG1 monoclonal antibody that binds specifically toCD3ε, thereby suppressing T-cell activation. The heavy chain constant regions are mutatedat two amino acid positions, L234A and L235A (see e.g. Sherry, N., et al., 2011. The Lancet,378(9790), pp.487-49). Teplizumab is a humanized version of the mouse monoclonal OKT3antibody, retaining the same binding region of OKT3 but with amino acids at positions 234 and235 of the human IgG1 Fc changed to alanine resulting in decreased Fc binding (see e.g.Masharani, U.B. and Becker, J., 2010. Expert opinion on biological therapy, 10(3), pp.459-465). The skilled person would be able to generate teplizumab derivatives using conservativemutations and / or knowledge of the mechanism of teplizumab binding to CD3.In some embodiments, the CD3 inhibitor is a fragment of teplizumab, or a derivative thereof.In some embodiments, the CD3 inhibitor is a teplizumab Fab, a teplizumab F(ab’)2, ateplizumab scFv, or a teplizumab sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is a teplizumab Fab, or a derivative thereof. In some embodiments, the CD3 inhibitor is, or is derived from, an anti-CD3 antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 81-86, or variants thereof. In other words, in some embodimentsthe CD3 inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 81-86, orvariants thereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 81 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 82 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 83 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 84 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 85 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 86 or a variant thereof.In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 81 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 82 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 83 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 84 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 85 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 86 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 87. In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 88. In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises an amino acid sequence having at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 87, and the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 88.In some embodiments, the CD3 inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 87, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 81 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 82 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 83 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 88, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 84 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 85 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 86 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 89 or 90.In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 91.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 89, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 91.In some embodiments, the CD3 inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 81, a HCDR2 having an amino acid sequence of SEQ ID NO: 82, and a HCDR3 having an amino acid sequence of SEQ ID NO: 83; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ IDNO: 91, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 84, a LCDR2 having an amino acid sequence of SEQ ID NO: 85, and a LCDR3 having an amino acid sequence of SEQ ID NO: 86.Name Example sequenceTeplizumab HCDR1 RYTMH (SEQ ID NO: 81)Teplizumab HCDR2 YINPSRGYTNYNQKVKD (SEQ ID NO: 82)Teplizumab HCDR3 YYDDHYCLDY (SEQ ID NO: 83)Teplizumab LCDR1 SASSSVSYMN (SEQ ID NO: 84)Teplizumab LCDR2 DTSKLAS (SEQ ID NO: 85)Teplizumab LCDR3 QQWSSNPFT (SEQ ID NO: 86)Teplizumab VH QVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYTMHWVRQAPGKGLEWIGYINPSRGYTNYNQKVKDRFTISRDNSKNTAFLQMDSLRPEDTGVYFCARYY DDHYCLDYWGQGTPVTVS (SEQ ID NO: 87)Teplizumab VL DIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQTPGKAPKRWIYDTSKLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSNPFTFGQG TKLQIT (SEQ ID NO: 88)Teplizumab VH +QVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYTMHWVRQAPGKGLEWIGY CH1 INPSRGYTNYNQKVKDRFTISRDNSKNTAFLQMDSLRPEDTGVYFCARYY DDHYCLDYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKV (SEQ ID NO: 89)Teplizumab heavy QVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYTMHWVRQAPGKGLEWIGY chain INPSRGYTNYNQKVKDRFTISRDNSKNTAFLQMDSLRPEDTGVYFCARYY DDHYCLDYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 90) Teplizumab light DIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQTPGKAPKRWIYDT chain SKLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSNPFTFGQG TKLQITRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC (SEQ ID NO: 91)VisilizumabIn some embodiments, the CD3 inhibitor is visilizumab, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is a visilizumab Fab, a visilizumab F(ab’)2, avisilizumab scFv, a visilizumab sdAb, or a derivative thereof. In some embodiments, the CD3inhibitor is a visilizumab Fab, or a derivative thereof.Visilizumab is a recombinant, humanized IgG2 monoclonal antibody that binds specifically toCD3ε, thereby suppressing T-cell activation. The heavy chain constant regions are mutatedat two amino acid positions, V234A and V237A (see e.g. Carpenter, P.A., et al., 2002.Blood, 99(8), pp.2712-2719). The skilled person would be able to generate visilizumabderivatives using conservative mutations and / or knowledge of the mechanism of visilizumab binding to CD3. In some embodiments, the CD3 inhibitor is a fragment of visilizumab, or a derivative thereof.In some embodiments, the CD3 inhibitor is a visilizumab Fab, a visilizumab F(ab’)2, avisilizumab scFv, or a visilizumab sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is a visilizumab Fab, or a derivative thereof. In some embodiments, the CD3 inhibitor is, or is derived from, an anti-CD3 antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 92-97, or variants thereof. In other words, in some embodimentsthe CD3 inhibitor comprises one or more CDR regions, selected from SEQ ID NOs: 92-97, orvariants thereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 92 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 93 or a variant thereof, and / ora HCDR3 having an amino acid sequence of SEQ ID NO: 94 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 95 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 96 or a variant thereof, and / ora LCDR3 having an amino acid sequence of SEQ ID NO: 97 or a variant thereof.In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 92 or a variant thereof, aHCDR2 having an amino acid sequence of SEQ ID NO: 93 or a variant thereof, and aHCDR3 having an amino acid sequence of SEQ ID NO: 94 or a variant thereof; and / or(ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 95 or a variant thereof, aLCDR2 having an amino acid sequence of SEQ ID NO: 96 or a variant thereof, and aLCDR3 having an amino acid sequence of SEQ ID NO: 97 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 98. In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 99. In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 98, and the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 99.In some embodiments, the CD3 inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 98, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQID NO: 92 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 93 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQ IDNO: 94 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 99, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 95 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 96 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 97 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein theheavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 100 or 101.In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises or consists of an amino acid sequence having at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 102.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 100, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 102.In some embodiments, the CD3 inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 100, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 92, a HCDR2 having an amino acid sequence of SEQ ID NO: 93, and a HCDR3 having an amino acid sequence of SEQ ID NO: 94; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 102, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 95, a LCDR2 having an amino acid sequence of SEQ ID NO: 96, and a LCDR3 having an amino acid sequence of SEQ ID NO: 97.Name Example sequenceVisilizumab HCDR1 SYTMH (SEQ ID NO: 92)Visilizumab HCDR2 YINPRSGYTHYNQKLKD (SEQ ID NO: 93)Visilizumab HCDR3 SAYYDYDGFAY (SEQ ID NO: 94)Visilizumab LCDR1 SASSSVSYMN (SEQ ID NO: 95)Visilizumab LCDR2 DTSKLAS (SEQ ID NO: 96)Visilizumab LCDR3 QQWSSNPPT (SEQ ID NO: 97)Visilizumab VH QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHYNQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSA YYDYDGFAYWGQGTLVTVS (SEQ ID NO: 98)Visilizumab VL DIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKRLIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGG TKVEIK (SEQ ID NO: 99)Visilizumab VH +QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGY CH1 INPRSGYTHYNQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSA YYDYDGFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT YTCNVDHKPSNTKVDKTV (SEQ ID NO: 100)Visilizumab heavy QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGY chain INPRSGYTHYNQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSA YYDYDGFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT YTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPAAAPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFR VVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPSK (SEQ ID NO: 101) Visilizumab light DIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKRLIYDT chain SKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC (SEQ ID NO: 102)Otelixizumab In some embodiments, the CD3 inhibitor is otelixizumab, or a fragment and / or derivativethereof. In some embodiments, the CD3 inhibitor is a otelixizumab Fab, a otelixizumab F(ab’)2,a otelixizumab scFv, a otelixizumab sdAb, or a derivative thereof. In some embodiments, theCD3 inhibitor is a otelixizumab Fab, or a derivative thereof.Otelixizumab is a recombinant, chimeric and humanized IgG1 monoclonal antibody that bindsspecifically to CD3ε, thereby suppressing T-cell activation. The heavy chain constant regions are mutated at N297A (see e.g. Aronson, R., et al, 2014. Diabetes care, 37(10), pp.2746- 2754). The skilled person would be able to generate otelixizumab derivatives usingconservative mutations and / or knowledge of the mechanism of otelixizumab binding to CD3.In some embodiments, the CD3 inhibitor is a fragment of otelixizumab, or a derivative thereof.In some embodiments, the CD3 inhibitor is a otelixizumab Fab, a otelixizumab F(ab’)2, aotelixizumab scFv, or a otelixizumab sdAb, or a derivative thereof. In some embodiments, theCD3 inhibitor is a otelixizumab Fab, or a derivative thereof. In some embodiments, the CD3 inhibitor is, or is derived from, an anti-CD3 antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 103-108, or variants thereof. In other words, in someembodiments the CD3 inhibitor comprises one or more CDR regions, selected from SEQ IDNOs: 103-108, or variants thereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 103 or a variant thereof,a HCDR2 having an amino acid sequence of SEQ ID NO: 104 or a variant thereof,and / or a HCDR3 having an amino acid sequence of SEQ ID NO: 105 or a variantthereof; and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 106 or a variant thereof,a LCDR2 having an amino acid sequence of SEQ ID NO: 107 or a variant thereof,and / or a LCDR3 having an amino acid sequence of SEQ ID NO: 108 or a variantthereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 103 or a variant thereof,a HCDR2 having an amino acid sequence of SEQ ID NO: 104 or a variant thereof, anda HCDR3 having an amino acid sequence of SEQ ID NO: 105 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 106 or a variant thereof,a LCDR2 having an amino acid sequence of SEQ ID NO: 107 or a variant thereof, anda LCDR3 having an amino acid sequence of SEQ ID NO: 108 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 109. In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 110. In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 109, and the light chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identityor 100% identity to SEQ ID NO: 110.In some embodiments, the CD3 inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 109, whereinthe amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 103 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 104 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQID NO: 105 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 110, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 106 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 107 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 108 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 111 or 112.In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein thelight chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 113.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 111, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 113.In some embodiments, the CD3 inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 111, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 103, a HCDR2 having an amino acid sequence of SEQ ID NO: 104, and a HCDR3 having an amino acid sequence of SEQ ID NO: 105; and / or (ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 113, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 106, a LCDR2 having an amino acid sequence of SEQ ID NO: 107, and a LCDR3 having an amino acid sequence of SEQ ID NO: 108. Name Example sequenceOtelixizumab HCDR1 SFPMA (SEQ ID NO: 103)Otelixizumab HCDR2 TISTSGGRTYYRDSVKG (SEQ ID NO: 104)Otelixizumab HCDR3 FRQYSGGFDY (SEQ ID NO: 105)Otelixizumab LCDR1 TLSSGNIENNYVH (SEQ ID NO: 106)Otelixizumab LCDR2 DDDKRPD (SEQ ID NO: 107)Otelixizumab LCDR3 HSYVSSFNV (SEQ ID NO: 108)Otelixizumab VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFPMAWVRQAPGKGLEWVSTISTSGGRTYYRDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKFR QYSGGFDYWGQGTLVTVS (SEQ ID NO: 109)Otelixizumab VL DIQLTQPNSVSTSLGSTVKLSCTLSSGNIENNYVHWYQLYEGRSPTTMIYDDDKRPDGVPDRFSGSIDRSSNSAFLTIHNVAIEDEAIYFCHSYVSSFNV FGGGTKLTVL (SEQ ID NO: 110)Otelixizumab VH +EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFPMAWVRQAPGKGLEWVST CH1 ISTSGGRTYYRDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKFR QYSGGFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKV (SEQ ID NO: 111)Otelixizumab heavy EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFPMAWVRQAPGKGLEWVST chain ISTSGGRTYYRDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKFR QYSGGFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYAS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 112) Otelixizumab light DIQLTQPNSVSTSLGSTVKLSCTLSSGNIENNYVHWYQLYEGRSPTTMIY chain DDDKRPDGVPDRFSGSIDRSSNSAFLTIHNVAIEDEAIYFCHSYVSSFNV FGGGTKLTVLRQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS (SEQ ID NO: 113)Muromonab-CD3 In some embodiments, the CD3 inhibitor is muromonab-CD3, or a fragment and / or derivativethereof. In some embodiments, the CD3 inhibitor is a muromonab-CD3 Fab, a muromonab-CD3 F(ab’)2, a muromonab-CD3 scFv, a muromonab-CD3 sdAb, or a derivative thereof. Insome embodiments, the CD3 inhibitor is a muromonab-CD3 Fab, or a derivative thereof.Muromonab-CD3 is a recombinant, murine monoclonal antibody that binds specifically toCD3ε, thereby suppressing T-cell activation (see e.g. Wilde, M.I. and Goa, K.L., 1996. Drugs,51, pp.865-894). The skilled person would be able to generate muromonab-CD3 derivativesusing conservative mutations and / or knowledge of the mechanism of muromonab-CD3binding to CD3 (see e.g. Kjer-Nielsen, L., et al., 2004. PNAS, 101(20), pp.7675-7680).In some embodiments, the CD3 inhibitor is a fragment of muromonab-CD3, or a derivativethereof. In some embodiments, the CD3 inhibitor is a muromonab-CD3 Fab, a muromonab-CD3 F(ab’)2, a muromonab-CD3 scFv, or a muromonab-CD3 sdAb, or a derivative thereof. Insome embodiments, the CD3 inhibitor is a muromonab-CD3 Fab, or a derivative thereof.In some embodiments, the CD3 inhibitor is, or is derived from, an anti-CD3 antibody (e.g. is aFab, F(ab’)2, scFv, or sdAb) wherein the antibody comprises one or more CDR regions,selected from SEQ ID NOs: 114-119, or variants thereof. In other words, in someembodiments the CD3 inhibitor comprises one or more CDR regions, selected from SEQ IDNOs: 114-119, or variants thereof. In some embodiments, the CD3 inhibitor comprises:(i) a HCDR1 having an amino acid sequence of SEQ ID NO: 114 or a variant thereof,a HCDR2 having an amino acid sequence of SEQ ID NO: 115 or a variant thereof,and / or a HCDR3 having an amino acid sequence of SEQ ID NO: 116 or a variantthereof; and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 117 or a variant thereof,a LCDR2 having an amino acid sequence of SEQ ID NO: 118 or a variant thereof,and / or a LCDR3 having an amino acid sequence of SEQ ID NO: 119 or a variantthereof. In some embodiments, the CD3 inhibitor comprises: (i) a HCDR1 having an amino acid sequence of SEQ ID NO: 114 or a variant thereof,a HCDR2 having an amino acid sequence of SEQ ID NO: 115 or a variant thereof, anda HCDR3 having an amino acid sequence of SEQ ID NO: 116 or a variant thereof;and / or (ii) a LCDR1 having an amino acid sequence of SEQ ID NO: 117 or a variant thereof,a LCDR2 having an amino acid sequence of SEQ ID NO: 118 or a variant thereof, anda LCDR3 having an amino acid sequence of SEQ ID NO: 119 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 120.In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein thelight chain comprises an amino acid sequence having at least 70%, at least 75%, at least 80%,at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least99% identity, or 100% identity to SEQ ID NO: 121. In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence having at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%,at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 120, and the light chaincomprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity or 100% identity to SEQ ID NO: 121.In some embodiments, the CD3 inhibitor comprises or consists of:(i) a heavy chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 120, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 114 or a variant thereof, a HCDR2 having an amino acid sequence of SEQ IDNO: 115 or a variant thereof, and a HCDR3 having an amino acid sequence of SEQID NO: 116 or a variant thereof; and / or(ii) a light chain comprising an amino acid sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 121, whereinthe amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 117 or a variant thereof, a LCDR2 having an amino acid sequence of SEQ IDNO: 118 or a variant thereof, and a LCDR3 having an amino acid sequence of SEQ IDNO: 119 or a variant thereof.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity, or 100% identity to SEQ ID NO: 122 or 123.In some embodiments, the CD3 inhibitor comprises or consists of a light chain, wherein thelight chain comprises or consists of an amino acid sequence having at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 124.In some embodiments, the CD3 inhibitor comprises or consists of a heavy chain and a lightchain, wherein the heavy chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 122, and the light chain comprises or consists of an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity or 100% identity to SEQ ID NO: 124.In some embodiments, the CD3 inhibitor comprises or consists of: (i) a heavy chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 122, wherein the amino acid sequence comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 114, a HCDR2 having an amino acid sequence of SEQ ID NO: 115, and a HCDR3 having an amino acid sequence of SEQ ID NO: 116; and / or(ii) a light chain comprising or consisting of an amino acid sequence having at least70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 124, wherein the amino acid sequence comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 117, a LCDR2 having an amino acid sequence of SEQ ID NO: 118, and a LCDR3 having an amino acid sequence of SEQ ID NO: 119. Name Example sequenceMuromonab-CD3 HCDR1 RYTMH (SEQ ID NO: 114)Muromonab-CD3 HCDR2 YINPSRGYTNYNQKFKD (SEQ ID NO: 115)Muromonab-CD3 HCDR3 YYDDHYCLDY (SEQ ID NO: 116)Muromonab-CD3 LCDR1 SASSSVSYMN (SEQ ID NO: 117)Muromonab-CD3 LCDR2 DTSKLAS (SEQ ID NO: 118)Muromonab-CD3 LCDR3 QQWSSNPFT (SEQ ID NO: 119)Muromonab-CD3 VH QVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSA VYYCARYYDDHYCLDYWGQGTTLTVS (SEQ ID NO: 120)Muromonab-CD3 VL QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWYQQKSGTSPKRWIYDTSKLASGVPAHFRGSGSGTSYSLTISGMEAEDAATYYCQQWSS NPFTFGSGTKLEIN (SEQ ID NO: 121)Muromonab-CD3 VH +QVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLE CH1 WIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSA VYYCARYYDDHYCLDYWGQGTTLTVSSAKTTAPSVYPLAPVCGGTT GSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDLYTLS SSVTVTSSTWPSQSITCNVAHPASSTKVDKKI (SEQ ID NO:122) Muromonab-CD3 heavyQVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLE chain WIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSA VYYCARYYDDHYCLDYWGQGTTLTVSSAKTTAPSVYPLAPVCGGTT GSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDLYTLS SSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ IDNO: 123) Muromonab-CD3 lightQIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWYQQKSGTSPKRW chain IYDTSKLASGVPAHFRGSGSGTSYSLTISGMEAEDAATYYCQQWSS NPFTFGSGTKLEINRADTAPTVSIFPPSSEQLTSGGASVVCFLNNF YPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDE YERHNSYTCEATHKTSTSPIVKSFNRNEC (SEQ ID NO: 124)Other anti-CD3 antibodiesOther suitable anti-CD3 antibodies, and fragments and / or derivatives thereof, are known inthe art.In some embodiments, the CD3 inhibitor is T3 / 4.A, or a fragment and / or derivative thereof. Insome embodiments, the CD3 inhibitor is a T3 / 4.A Fab, a T3 / 4.A F(ab’)2, a T3 / 4.A scFv, aT3 / 4.A sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is a T3 / 4.A Fab,or a derivative thereof.T3 / 4.A (also known as CLB-T3 / 4.A) is a murine IgA mAb specific for human CD3. T3 / 4.A isnon-mitogenic for human peripheral blood mononuclear cells (PBMC) in vitro. The mAb was developed as a switch variant antibody, derived from an originally IgG1-producing hybridoma(see e.g. Meijer, R.T., et al., 2003. Clinical & Experimental Immunology, 133(3), pp.485-492).In some embodiments, the CD3 inhibitor is YTH12.5, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is a YTH12.5 Fab, a YTH12.5 F(ab’)2, a YTH12.5scFv, a YTH12.5 sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is aYTH12.5 Fab, or a derivative thereof.YTH12.5 a rat CD3 antibody which has been humanized to provide a aglycosylated IgG1antibody (e.g. CAMPATH 3) (see e.g. Friend, P.J., et al., 1999. Transplantation, 68(11), pp.1632-1637). In some embodiments, the CD3 inhibitor is HuM291, or a fragment and / or derivative thereof.In some embodiments, the CD3 inhibitor is a HuM291Fab, a HuM291F(ab’)2, a HuM291scFv,a HuM291sdAb, or a derivative thereof. In some embodiments, the CD3 inhibitor is aHuM291Fab, or a derivative thereof.HuM291 is a humanized IgG2 antibody that was engineered to have less mitogenic activity inhumans compared with murine anti-CD3 antibodies (see e.g. Norman, D.J., et al., 2000.Transplantation, 70(12), pp.1707-1712). Other CD3 inhibitors Other suitable CD3 inhibitors include CD3 T-cell engagers, CD3-specific DNA aptamers, and CD3-specific RNA aptamers (see e.g. Menon, A.P., et al., 2023. Cancers, 15(4), p.1189). CD3 T-cell engagersIn some embodiments, the CD3 inhibitor is a CD3 T-cell engager or a fragment and / orderivative thereof. T-cell engagers are designed to bind to a target antigen expressed on a cancer cell and to a trigger molecule on T cells, such as CD3. Typically, T-cell engagers are based on bispecificmonoclonal antibodies (bsAbs). A bispecific T-cell engager (BiTE) is a sub-class of T-cell engaging bsAbs with promising clinical results in the treatment of cancers (see e.g. Huehls, A.M., et al., 2015. Immunology and cell biology, 93(3), pp.290-296; Zhou, S., et al., 2021. Biomarker Research, 9(1), p.38; and Tian, Z., et al., 2021. Journal of Hematology & Oncology, 14(1), pp.1-18). Examples of CD3 T-cell engagers include blinatumomab, tebentafusp, talquetamab, mosunetuzumab, glofitamab, epcoritamab, odronextamab, teclistamab, cevostamab, and lotetuzumab. In some embodiments, the CD3 inhibitor is a CD3-binding fragment from a CD3 T-cellengager, or a derivative thereof. For example, the CD3-binding fragment may be a single-chain variable fragment (scFv). CD3-specific aptamers In some embodiments, the CD3 inhibitor is a CD3-specific aptamer. In some embodiments, the CD3 inhibitor is a CD3-specific DNA aptamer. In some embodiments, the CD3 inhibitor is a CD3-specific RNA aptamer.A DNA aptamer selected against the human CD3ε complex by ligand-guided selection (LIGS)has been described and US. Patent Application No. 17 / 629,943 describes RNA aptamersselected against recombinant CD3ε / γ and CD3ε / δ proteins (see e.g. Menon, A.P., et al., 2023.Cancers, 15(4), p.1189). Example nucleotide sequencesThe CD3 inhibitor may be encoded by any suitable nucleotide sequence. In someembodiments, the nucleotide sequence is codon-optimised, for example codon-optimised forexpression in humans.In preferred embodiments, the CD3 inhibitor is an anti-CD3 antigen-binding fragment (Fab).Suitably, a nucleotide sequence encoding an anti-CD3 Fab may comprise from 5’ to 3’: a firstsignal sequence; a nucleotide encoding a heavy chain (e.g. VH + CH1); a linker sequence; asecond signal sequence; and a nucleotide encoding a light chain. Suitably, a nucleotidesequence encoding an anti-CD3 Fab may comprise from 5’ to 3’: a first signal sequence; anucleotide encoding a light chain; a linker sequence; a second signal sequence; and anucleotide encoding a heavy chain (e.g. VH + CH1).Heavy chains and light chainsThe nucleotide encoding a heavy chain (e.g. VH + CH1) and the nucleotide encoding a lightchain may encode any heavy chain (e.g. VH + CH1) and light chain combination describedherein. For example, the nucleotide sequence encoding an anti-CD3 Fab may comprise from5’ to 3’: (a) a first signal sequence; a nucleotide encoding a foralumab heavy chain (e.g. VH +CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a foralumab light chain, or a derivative thereof; (b) a first signal sequence; a nucleotide encoding a teplizumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a teplizumab light chain, or a derivative thereof; (c) a first signal sequence; a nucleotide encoding a visilizumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a visilizumab light chain, or a derivative thereof; (d) a first signal sequence; a nucleotide encoding an otelixizumab heavy chain (e.g.VH + CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an otelixizumab light chain, or a derivative thereof; (e) a first signal sequence; a nucleotide encoding a muromonab-CD3 heavy chain (e.g.VH + CH1), or a derivative thereof; a linker sequence; a second signal sequence; and anucleotide encoding a muromonab-CD3 light chain, or a derivative thereof;(f) a first signal sequence; a nucleotide encoding a foralumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a foralumab heavy chain (e.g. VH + CH1), or a derivative thereof;(g) a first signal sequence; a nucleotide encoding a teplizumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a teplizumab heavy chain (e.g. VH + CH1), or a derivative thereof;(h) a first signal sequence; a nucleotide encoding a visilizumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a visilizumab heavy chain (e.g. VH + CH1), or a derivative thereof;(i) a first signal sequence; a nucleotide encoding an otelixizumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding an otelixizumab heavy chain (e.g. VH + CH1), or a derivative thereof; or (j) a first signal sequence; a nucleotide encoding a muromonab-CD3 light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a muromonab-CD3 heavy chain (e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab may comprisefrom 5’ to 3’: a first signal sequence; a nucleotide encoding a foralumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a foralumab light chain, or a derivative thereof. In some embodiments, the nucleotidesequence encoding an anti-CD3 Fab may comprise from 5’ to 3’: a first signal sequence; anucleotide encoding a foralumab light chain, or a derivative thereof; a linker sequence; asecond signal sequence; and a nucleotide encoding a foralumab heavy chain (e.g. VH + CH1),or a derivative thereof.In some embodiments, the nucleotide sequence encoding a foralumab heavy chain (e.g. VH+ CH1) comprises or consists of a nucleotide sequence having at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 125. In some embodiments, thenucleotide sequence encoding a foralumab heavy chain (e.g. VH + CH1) comprises orconsists of SEQ ID NO: 125. caggtgcagttggtggagagcggcggcggggtggtgcagcccggccggagcctgcggctgtc ttgtgccgctagcggattcaagttctctggctacggcatgcactgggtgcgccaggcacctg gcaagggcctggagtgggtggccgtgatctggtacgacggctccaagaaatattacgtggat tctgtgaagggacgctttacaatctcccgcgacaatagcaagaacaccctgtatctgcagat gaactccctgagggccgaggacacagccgtgtattactgcgcccggcagatgggctactggc actttgatctgtggggcagaggcaccctggtgacagtgtctagcgccagcaccaaggggcct agcgtgttccccctggccccctcttccaagtcaacctccgggggcaccgccgccctgggctg cctggtgaaagactattttcctgagcctgtgacagtgtcttggaactccggggccctgactt ctggcgtgcatacatttccagcagtgctgcagtcctccgggctgtactctctgagctccgtg gtgactgtgcctagcagctctctggggacacagacctacatctgtaatgtgaaccacaaacc cagcaataccaaggtggacaagagagtgtga Example nucleotide sequence encoding a foralumab heavy chain (VH+ CH1) (SEQ ID NO: 125)In some embodiments, the nucleotide sequence encoding a foralumab light chain comprisesor consists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 126. In some embodiments, nucleotide sequence encoding aforalumab light chain comprises or consists of SEQ ID NO: 126.gagattgtgctgacccagagcccagctaccctgagcctgtcccccggcgagcgggccacact gagctgcagagcctcacagagcgtgtcctcctacctggcttggtaccagcagaagccaggcc aggctcctagactgctgatttacgacgcctcaaacagagccaccggcattcccgcaagattc agcggctctggatctgggacagacttcacactgaccattagcagcctggagcccgaggattt tgccgtgtattactgtcagcagagatcaaactggccacctctgacatttggcggggggacca aggtggaaattaaaagaaccgtggccgccccaagcgtgttcatctttccccccagcgacgag cagctgaaatccgggactgcctctgtggtgtgcctgctgaacaacttttacccaagagaagc caaggtgcagtggaaggtggacaatgccctgcagagtggaaattcccaggagtctgtgaccg agcaggatagcaaagacagcacatactcactgagctccaccctgaccctgagcaaggccgac tacgagaagcacaaggtgtacgcctgcgaggtgacccaccagggcctgagcagtcccgtgac caagtcatttaatagaggcgagtgttga Example nucleotide sequence encoding a foralumab light chain(SEQ ID NO: 126)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab may comprisefrom 5’ to 3’: a first signal sequence; a nucleotide encoding a teplizumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a teplizumab light chain, or a derivative thereof. In some embodiments, thenucleotide sequence encoding an anti-CD3 Fab may comprise from 5’ to 3’: a first signalsequence; a nucleotide encoding a teplizumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a teplizumab heavy chain (e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding a teplizumab heavy chain (e.g. VH+ CH1) comprises or consists of a nucleotide sequence having at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 127. In some embodiments, nucleotidesequence encoding a teplizumab heavy chain (e.g. VH + CH1) comprises or consists of SEQID NO: 127. caggtgcagctggtgcagagcggcggcggggtggtgcagcctggcaggtctctgagactgtc ctgcaaggccagcgggtacaccttcacccggtacaccatgcattgggtgcgccaggcaccag gaaaggggctggagtggatcgggtacatcaacccctcaagagggtacaccaactacaatcag aaggtgaaggaccggttcaccatctccagagacaactccaagaataccgccttcctgcagat ggactccctccggccagaggataccggcgtgtacttttgcgccaggtactatgatgatcact actgcctggattactggggccaggggacccctgtgacagtgtcaagcgcctctaccaaaggc ccctcagtgttcccactggccccaagcagcaagtctaccagcggcggcaccgccgctctggg gtgcctggtgaaggactacttccccgaacccgtgaccgtgagctggaactccggtgccctga catctggggtgcacacattcccagccgtgctgcagtctagcggcctgtatagcctgagctct gtggtgactgtgccaagctcctccctggggacccagacctacatttgtaacgtgaaccataa accatctaacaccaaagtggacaagaaggtgtag Example nucleotide sequence encoding a teplizumab heavy chain (VH + CH1) (SEQ ID NO: 127)In some embodiments, the nucleotide sequence encoding a teplizumab light chain comprisesor consists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 128. In some embodiments, nucleotide sequence encoding ateplizumab light chain comprises or consists of SEQ ID NO: 128. gacatccagatgacccagtccccctccagcctgagcgcctctgtgggcgaccgggtgacaat tacatgttcagcctcatccagcgtgagctatatgaattggtaccagcagaccccaggcaagg cccctaagagatggatctacgacaccagcaagctggcctctggcgtgcctagtcggttcagc gggtccggctccggaaccgattacaccttcaccatctcatcactgcagcctgaggacatcgc cacctactactgccagcagtggtcttctaacccattcactttcggccagggcaccaagctgc agatcacacgcaccgtggccgccccttctgtgttcatcttcccaccttccgatgaacagctg aagtccggcacagccagcgtggtgtgcctgctgaacaacttctatcccagggaggccaaggt gcagtggaaagtggataatgcactgcagagcggcaactcccaggagagcgtgaccgagcaag actctaaggactctacttattctctgtcatccaccctgaccctgagcaaggccgactacgag aagcacaaagtgtacgcctgcgaagtgacacaccaggggctgagcagccctgtgaccaagag cttcaatagaggagaatgctga Example nucleotide sequence encoding a teplizumab light chain (SEQ ID NO: 128)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab may comprisefrom 5’ to 3’: a first signal sequence; a nucleotide encoding a visilizumab heavy chain (e.g. VH+ CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a visilizumab light chain, or a derivative thereof. In some embodiments, thenucleotide sequence encoding an anti-CD3 Fab may comprise from 5’ to 3’: a first signalsequence; a nucleotide encoding a visilizumab light chain, or a derivative thereof; a linkersequence; a second signal sequence; and a nucleotide encoding a visilizumab heavy chain(e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding a visilizumab heavy chain (e.g. VH+ CH1) comprises or consists of a nucleotide sequence having at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 129. In some embodiments, thenucleotide sequence encoding a visilizumab heavy chain (e.g. VH + CH1) comprises orconsists of SEQ ID NO: 129. caggtgcagctggtgcagagcggcgccgaagtgaagaagccaggagcctccgtgaaggtgtc ttgtaaagcctcaggttatactttcatctcatataccatgcactgggtgagacaggcccccg ggcagggccttgagtggatgggatacattaaccctcgctccggctacacccattataatcag aagctgaaggacaaggccaccctgaccgctgacaagagcgcctccactgcctatatggagct gagcagcctgcggtccgaagacaccgccgtgtactactgtgccaggtctgcctactacgact acgatgggtttgcctactggggccagggcacactggtgacagtgagcagcgccagcaccaag ggccccagcgtgtttccactggccccctgcagcaggagcacctccgagagcaccgccgctct gggatgcctcgtgaaggactatttccccgagcccgtgacagtgagctggaactccggagcac tgacctccggcgtgcatacctttcccgccgtgctgcagagcagcggcctgtattccctgagc agcgtggtgaccgtgcctagcagcaatttcgggacacagacatacacatgtaacgtggatca taagccttcaaacactaaggtggacaagacagtgtaa Example nucleotide sequence encoding a visilizumab heavy chain(VH + CH1) (SEQ ID NO: 129)In some embodiments, the nucleotide sequence encoding a visilizumab light chain comprisesor consists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 130. In some embodiments, nucleotide sequence encoding avisilizumab light chain comprises or consists of SEQ ID NO: 130. gatattcagatgacacagagccctagctccctgagcgcctccgtgggggacagagtgacaat cacatgcagcgcttcatcctccgtgtcttacatgaattggtaccagcagaagcccggcaagg ctcccaagaggctgatctacgacaccagcaaactggcctctggcgtgccctctcgctttagc ggctccgggtccggcaccgacttcacactgaccatctcttctctgcaacccgaggattttgc cacttactactgtcagcagtggtcctccaacccccccactttcggcggaggcaccaaggtgg agatcaagcggacagtggctgcccccagcgttttcatcttcccaccaagcgacgagcagctg aaaagcggcacagctagcgtggtgtgcctgctgaataacttctacccccgggaggccaaggt gcagtggaaggtggataacgccctgcagtccgggaacagccaggagtcagtgaccgagcagg actctaaggattccacctacagcctgagcagcaccctgaccctgtccaaagcagactacgag aaacacaaggtgtacgcctgcgaggtgacacaccagggcctgtcttcccccgtgaccaagtc cttcaatcggggcgagtgttga Example nucleotide sequence encoding a visilizumab light chain (SEQ ID NO: 130)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab may comprisefrom 5’ to 3’: a first signal sequence; a nucleotide encoding a otelixizumab heavy chain (e.g.VH + CH1), or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a otelixizumab light chain, or a derivative thereof. In some embodiments,the nucleotide sequence encoding an anti-CD3 Fab may comprise from 5’ to 3’: a first signalsequence; a nucleotide encoding a otelixizumab light chain, or a derivative thereof; a linker sequence; a second signal sequence; and a nucleotide encoding a otelixizumab heavy chain (e.g. VH + CH1), or a derivative thereof.In some embodiments, the nucleotide sequence encoding a otelixizumab heavy chain (e.g.VH + CH1) comprises or consists of a nucleotide sequence having at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 131. In some embodiments, thenucleotide sequence encoding a otelixizumab heavy chain (e.g. VH + CH1) comprises orconsists of SEQ ID NO: 131. gaggtgcagctgctggagagcggagggggcctggtgcagccaggtggctctctgaggctgtc atgcgctgccagtggcttcaccttctccagctttcctatggcctgggtgcggcaggcccccg gcaagggtctggaatgggtgagcaccatcagcacctccgggggcaggacatactacagagac agcgtgaagggcagattcaccatcagccgagataattccaaaaacacactctacctgcagat gaatagcctgagagctgaagatactgccgtgtactactgcgccaagttccggcagtactccg gaggatttgattattggggccagggcaccctggtgacagtgtcctcagccagcaccaagggc cccagcgtgtttcccctggcccccagctctaagtccacctcaggcggcaccgccgccctggg gtgcctggtgaaggactatttcccagaacctgtgacagtgagctggaattccggagctctca ccagcggcgtgcacacatttcctgccgtgctgcagagcagcggactgtatagtctgagttct gtggtgaccgtgccctcctcctccctgggcacccagacctatatctgtaacgtgaaccacaa acccagcaacaccaaagtggacaagaaggtgtgaExample nucleotide sequence encoding a otelixizumab heavy chain(VH + CH1) (SEQ ID NO: 131)In some embodiments, the nucleotide sequence encoding a otelixizumab light chaincomprises or consists of a nucleotide sequence having at least 70%, at least 75%, at least80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 132. In some embodiments, nucleotidesequence encoding a otelixizumab light chain comprises or consists of SEQ ID NO: 132.gacatccagctgacacagcctaatagtgtgtctacctctctggggagcaccgtgaagctgtc ctgcaccctgtctagcggcaacatcgaaaacaactacgtgcactggtaccagctgtacgagg gcagaagcccaaccaccatgatttatgatgacgataagcggcctgatggcgtgcccgaccgg ttcagcggcagcattgacagatcctccaacagtgcctttctgaccatccacaacgtggctat cgaggacgaggccatttacttttgccactcctatgtgagctctttcaatgtcttcggaggcg ggaccaagctgaccgtgctgagacagccaaaagccgccccttccgtgaccctgttcccaccc tccagcgaggaactgcaggccaataaggccacactggtgtgcctgatctccgacttctatcc cggagccgtgaccgtcgcttggaaggccgacagcagccccgtcaaagccggcgtggagacaa ccaccccctccaaacagagcaataataagtatgcagccagcagctatctgtctctgacgccc gagcagtggaagagccacagaagctattcctgccaggtgacacacgagggcagcacagtgga gaagaccgtggcccccacagagtgtagctga Example nucleotide sequence encoding a otelixizumab light chain (SEQ ID NO: 132)Example anti-CD3 Fab sequencesIn some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence comprising or consisting of from 5’ to 3’: an amino acid sequence having atleast 70% identity to SEQ ID NO: 1, an amino acid sequence having at least 70% identity to SEQ ID NO: 76, an amino acid sequence having at least 70% sequence identity to any of SEQ ID NOs: 6-9, an amino acid sequence having at least 70% identity to SEQ ID NO: 1, and anamino acid sequence having at least 70% identity to SEQ ID NO: 77.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity toSEQ ID NO: 133. In some embodiments, the nucleotide sequence encoding an anti-CD3 Fabencodes the amino acid sequence of SEQ ID NO: 133. MATGSRTSLLLAFGLLCLPWLQEGSAQVQLVESGGGVVQPGRSLRLSCAASGFKFSGYGMHW VRQAPGKGLEWVAVIWYDGSKKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR QMGYWHFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVRKRRSG SGATNFSLLKQAGDVEENPGPMATGSRTSLLLAFGLLCLPWLQEGSAEIVLTQSPATLSLSP GERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISS LEPEDFAVYYCQQRSNWPPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC Example foralumab Fab amino acid sequence (SEQ ID NO: 133)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of from 5’ to 3’: a nucleotide sequence having at least 70% identity to any of SEQ IDNOs: 2-5, a nucleotide sequence having at least 70% identity to SEQ ID NO: 125, a nucleotidesequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, a nucleotidesequence having at least 70% identity to any of SEQ ID NOs: 2-5, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 126.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 134. In some embodiments, the nucleotide sequenceencoding an anti-CD3 Fab comprises or consists of SEQ ID NO: 134.atggctaccggctctaggacctcactgctgctggccttcggcctgctgtgcctgccctggct gcaggagggcagcgcccaggtccagctggtggagagcggcgggggcgtggtgcagcccggca gaagcctgcggctgagctgtgccgccagcggattcaagtttagcggctacgggatgcactgg gtcaggcaggctcctggaaagggactggagtgggtggcagtgatctggtatgatggctccaa gaaatactacgtcgacagcgtgaaaggacgcttcaccatcagcagggataacagcaagaata cactgtacctgcagatgaacagcctgagagcagaggatacagccgtgtactactgcgccagg cagatgggctactggcacttcgacctatgggggaggggtacactggtgaccgtgagctccgc atccaccaaagggccctctgtgttccccctggccccctccagcaagtccacctctggaggaa ccgctgccctgggctgtctggtgaaagattattttccagagcctgtcaccgtgtcttggaac tccggcgctctgacatccggcgtgcacacattccccgccgtgctgcagagctctggcctcta cagcctgtcttctgtggtgacagtgcccagctccagcctggggacccagacctatatctgca acgtgaaccacaagccatctaacaccaaagtggataaacgggtgaggaagaggaggtccggc tccggcgccacaaacttttctctgctgaagcaggccggggacgtggaggagaaccccggccc aatggccaccggttctagaaccagcctgctgctggcctttggcctgctgtgcctgccttggc tgcaggagggcagcgctgaaattgtgctgacacagtctcccgccaccctgtccctgtccccc ggcgagagggccacactgagctgtagggccagccagtccgtgagcagctatctggcctggta ccagcagaaacccggacaggccccaagactgctgatttatgacgcctccaacagagctacgg gcatccccgctcgcttttccggcagcggaagcgggacagacttcactctgaccattagctca ctggaacccgaggacttcgctgtgtattattgtcagcaacgcagcaactggccccctctgac cttcggggggggaacaaaagtggagattaaaagaaccgtggccgctccttccgtgttcatct ttcctccatccgatgagcagctgaagtccggtacagccagcgttgtgtgcctgctgaacaac ttttatccccgggaggctaaagtgcagtggaaagtggacaatgccctgcagagcggaaatag ccaggagtcagtgaccgaacaggatagcaaggattccacctacagcctgagcagcaccctga cactgtctaaagccgactatgagaagcacaaggtgtatgcctgcgaggtgactcaccagggc ctgagttctcccgtgaccaagtctttcaacaggggagaatgctga Example foralumab Fab nucleotide sequence (SEQ ID NO: 134)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence comprising or consisting of from 5’ to 3’: an amino acid sequence having atleast 70% identity to SEQ ID NO: 1, an amino acid sequence having at least 70% identity toSEQ ID NO: 87, an amino acid sequence having at least 70% sequence identity to any of SEQID NOs: 6-9, an amino acid sequence having at least 70% identity to SEQ ID NO: 1, and anamino acid sequence having at least 70% identity to SEQ ID NO: 88.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity toSEQ ID NO: 135. In some embodiments, the nucleotide sequence encoding an anti-CD3 Fabencodes the amino acid sequence of SEQ ID NO: 135. MATGSRTSLLLAFGLLCLPWLQEGSAQVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYTMHW VRQAPGKGLEWIGYINPSRGYTNYNQKVKDRFTISRDNSKNTAFLQMDSLRPEDTGVYFCAR YYDDHYCLDYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVRKRRS GSGATNFSLLKQAGDVEENPGPMATGSRTSLLLAFGLLCLPWLQEGSADIQMTQSPSSLSAS VGDRVTITCSASSSVSYMNWYQQTPGKAPKRWIYDTSKLASGVPSRFSGSGSGTDYTFTISS LQPEDIATYYCQQWSSNPFTFGQGTKLQITRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC Example teplizumab Fab amino acid sequence (SEQ ID NO: 135)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of from 5’ to 3’: a nucleotide sequence having at least 70% identity to any of SEQ IDNOs: 2-5, a nucleotide sequence having at least 70% identity to SEQ ID NO: 127, a nucleotidesequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, a nucleotidesequence having at least 70% identity to any of SEQ ID NOs: 2-5, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 128.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 136. In some embodiments, the nucleotide sequenceencoding an anti-CD3 Fab comprises or consists of SEQ ID NO: 136.atggctaccggctccagaacctccctgctgctggctttcggcctgctgtgtctgccttggct gcaggaaggctccgcccaggtgcagctggtgcagtccggaggaggagtggtgcagcccggca gatcccttcgcctgagctgcaaggcttctggctacacattcaccaggtacaccatgcactgg gtgagacaggcccccggaaagggcctggagtggattggctatattaaccccagcaggggata caccaattacaatcagaaggtcaaggacaggttcaccatcagcagggacaacagtaagaata cagcattcctgcagatggacagcctgagaccagaggatacaggcgtgtatttttgcgccagg tattacgatgaccactactgtctggactactgggggcagggaacaccagtgaccgtgagctc cgccagcacaaagggcccctctgtgttcccactggccccctccagcaagagcacctccggcg gaaccgccgccctgggctgtctggtgaaggactactttcctgaacctgtgacagtcagctgg aactcaggcgccctgaccagcggagtgcataccttccccgccgtgctgcagagctctggcct gtactccctgagcagcgtggtcacagtgcccagcagcagcctgggcacacagacttatatct gcaacgtgaaccacaagcctagcaacactaaggtcgataaaaaggtcagaaagagaagatca ggcagcggcgctaccaacttcagcttgctgaagcaggccggcgacgtggaggagaaccccgg cccaatggcaaccggctcaaggacttccctgctcctggctttcgggctgctgtgtctgccct ggctgcaggaggggagcgccgacatccagatgacccagtctccatcttccctgagcgccagc gtgggcgatcgggtcacaatcacatgttctgccagctccagcgtgagctacatgaattggta ccagcagacccccggcaaggctcccaaaaggtggatttacgacacctcaaagctggcaagcg gagttccctctcggttctccggcagcggatccggaaccgactacaccttcacaatcagctcc ctgcagcctgaagacatcgctacatattactgccagcagtggagcagcaaccctttcacctt cggccagggcacaaagctgcagatcaccaggaccgtggctgcccctagcgtgttcatcttcc ccccctcagatgagcagctcaagagcggcacagcctcagtggtgtgcctcctgaacaatttc taccccagagaagcaaaggtgcagtggaaggtggacaatgccctgcagtccggcaactctca ggagagcgtgacagaacaggacagtaaagactccacatatagcctgtctagcaccctgaccc tgtccaaggccgactacgagaagcacaaggtctacgcttgcgaggtgacacaccaagggctg tcttcccctgtcaccaagtcatttaatagaggcgaatgctga Example teplizumab Fab nucleotide sequence (SEQ ID NO: 136)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence comprising or consisting of from 5’ to 3’: an amino acid sequence having atleast 70% identity to SEQ ID NO: 1, an amino acid sequence having at least 70% identity to SEQ ID NO: 98, an amino acid sequence having at least 70% sequence identity to any of SEQID NOs: 6-9, an amino acid sequence having at least 70% identity to SEQ ID NO: 1, and anamino acid sequence having at least 70% identity to SEQ ID NO: 99.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity toSEQ ID NO: 137. In some embodiments, the nucleotide sequence encoding an anti-CD3 Fabencodes the amino acid sequence of SEQ ID NO: 137.MATGSRTSLLLAFGLLCLPWLQEGSAQVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHW VRQAPGQGLEWMGYINPRSGYTHYNQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCAR SAYYDYDGFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVRKRR SGSGATNFSLLKQAGDVEENPGPMATGSRTSLLLAFGLLCLPWLQEGSADIQMTQSPSSLSA SVGDRVTITCSASSSVSYMNWYQQKPGKAPKRLIYDTSKLASGVPSRFSGSGSGTDFTLTIS SLQPEDFATYYCQQWSSNPPTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC Example visilizumab Fab amino acid sequence (SEQ ID NO: 137)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of from 5’ to 3’: a nucleotide sequence having at least 70% identity to any of SEQ IDNOs: 2-5, a nucleotide sequence having at least 70% identity to SEQ ID NO: 129, a nucleotidesequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, a nucleotidesequence having at least 70% identity to any of SEQ ID NOs: 2-5, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 130.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 138. In some embodiments, the nucleotide sequenceencoding an anti-CD3 Fab comprises or consists of SEQ ID NO: 138.atggccaccggctctcggacctccctgctgctggccttcggcctgctgtgtctgccctggct ccaggaaggctccgcccaggtgcagctggtgcagtctggggccgaagtgaagaaacccggcg ccagcgttaaggtgagctgcaaggcctctggctacaccttcatcagctacaccatgcactgg gtgagacaggcccccggccagggactggaatggatggggtatatcaacccaaggtctgggta cacccactacaaccagaaactgaaagataaggccacgctgaccgccgataagtctgccagca ccgcctacatggagctgagtagcctgcggtcagaggataccgccgtgtactactgcgccaga tctgcctattacgactacgacgggtttgcctactggggacagggaacactggtgaccgtgag ctctgcttctacgaagggcccatccgtgttcccactggccccctgcagccgcagcaccagcg agtccaccgccgccctgggatgcctggtgaaagactactttccagagcctgtgaccgtgtcc tggaattccggcgcccttaccagcggagtgcacacctttccagccgttctgcagtccagcgg cctgtactctctgtctagcgtggtgaccgtgcccagctccaattttggcacccagacctaca cctgcaacgtggaccacaagccatccaacactaaagtcgataagactgtgcgcaagagaaga agcggcagcggcgccaccaatttttccctgctgaagcaggctggagacgtcgaggagaaccc agggcctatggctaccggcagccggacttccctgctgctggcctttgggctgctgtgcctgc cctggctccaggagggcagcgccgatatccagatgactcagtccccatcctcactgtccgcc agcgtgggagatcgggtgactatcacatgtagcgcaagcagcagcgtgagctatatgaactg gtatcagcagaagccaggaaaggccccaaagaggctgatctatgacacctccaaactggcca gtggcgtgccttcacgtttctccggatctggctctgggaccgacttcaccctgacaatctcc agcctgcagccagaggatttcgctacttactactgccagcagtggagctctaacccaccaac cttcggcggcggcaccaaggtggagatcaagagaaccgtggccgccccatccgtgttcattt tccctccctctgacgagcagctgaagagcggcaccgcaagtgtggtgtgcctcctgaataat ttctaccctcgcgaagccaaggtgcagtggaaggtggacaacgccctgcagtccggcaatag ccaggagtccgtgaccgaacaggacagcaaggactccacatactccctgagcagcaccctga cactgagcaaggctgactacgagaaacacaaggtctatgcctgcgaggtgacccatcagggc ctgtcttcccctgtgacaaaaagctttaacagaggcgaatgttga Example visilizumab Fab nucleotide sequence (SEQ ID NO: 138)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence comprising or consisting of from 5’ to 3’: an amino acid sequence having atleast 70% identity to SEQ ID NO: 1, an amino acid sequence having at least 70% identity to SEQ ID NO: 109, an amino acid sequence having at least 70% sequence identity to any of SEQ ID NOs: 6-9, an amino acid sequence having at least 70% identity to SEQ ID NO: 1, andan amino acid sequence having at least 70% identity to SEQ ID NO: 110.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab encodes an aminoacid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity toSEQ ID NO: 139. In some embodiments, the nucleotide sequence encoding an anti-CD3 Fabencodes the amino acid sequence of SEQ ID NO: 139. MATGSRTSLLLAFGLLCLPWLQEGSAEVQLLESGGGLVQPGGSLRLSCAASGFTFSSFPMAW VRQAPGKGLEWVSTISTSGGRTYYRDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK FRQYSGGFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVRKRRS GSGATNFSLLKQAGDVEENPGPMATGSRTSLLLAFGLLCLPWLQEGSADIQLTQPNSVSTSL GSTVKLSCTLSSGNIENNYVHWYQLYEGRSPTTMIYDDDKRPDGVPDRFSGSIDRSSNSAFL TIHNVAIEDEAIYFCHSYVSSFNVFGGGTKLTVLRQPKAAPSVTLFPPSSEELQANKATLVC LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS Example otelixizumab Fab amino acid sequence (SEQ ID NO: 139)In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of from 5’ to 3’: a nucleotide sequence having at least 70% identity to any of SEQ IDNOs: 2-5, a nucleotide sequence having at least 70% identity to SEQ ID NO: 131, a nucleotidesequence having at least 70% sequence identity to SEQ ID NO: 10 or 11, a nucleotidesequence having at least 70% identity to any of SEQ ID NOs: 2-5, and a nucleotide sequence having at least 70% identity to SEQ ID NO: 132.In some embodiments, the nucleotide sequence encoding an anti-CD3 Fab comprises orconsists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity,or 100% identity to SEQ ID NO: 140. In some embodiments, the nucleotide sequenceencoding an anti-CD3 Fab comprises or consists of SEQ ID NO: 140.atggccaccgggtctaggaccagcctgctgctggccttcggcctgctgtgtctgccctggct gcaggagggctccgccgaggtgcagctgctggaatcaggaggcggcctggtgcagcctggag gcagcctgcgcctgtcatgcgcagcatctgggttcaccttctcctctttccctatggcctgg gtgagacaggcccccgggaagggtctggagtgggtgtctaccatttctacatctggaggccg gacctactacagagatagcgtgaagggccggttcaccatttctagagacaattccaagaata ccctgtacctgcaaatgaatagcctgagagccgaagacactgccgtgtattactgcgctaag ttccgccagtactccggcggattcgactactggggccagggcaccctagtgacagtgtcctc cgccagcacaaaaggcccctccgtgtttccactggccccctcttccaagtctacttcaggag gcacagccgccctgggctgcctggtgaaagattacttccctgagcccgtgaccgtgtcctgg aactcaggagccctgaccagcggcgtgcacaccttcccagccgtgctgcagtcctctggcct gtacagcctgtccagcgtggtgactgtgccaagctccagcctgggcacccagacctacatct gcaatgtgaaccacaagcctagcaacacaaaggtggacaagaaagtgagaaaaagaaggtct ggctccggcgcgaccaacttctccctgctgaaacaggccggggacgtggaggagaaccctgg cccaatggccacaggctctagaaccagcctgctgctggctttcggcctgctgtgcctgccct ggctgcaggaaggctccgccgatatccagcttacccagcccaatagcgtgtccacgtcactg ggttccacagtcaagctgagttgtactctgagcagtgggaatattgagaataactacgtgca ctggtatcagctgtacgagggtaggagccctacaaccatgatctatgacgacgacaagcgcc cagacggcgtgcctgacagattctccggctcaatcgacagatccagtaactccgccttcctg acaattcacaacgtggctattgaggacgaggccatttacttttgccactcctacgtgagcag cttcaatgtgttcggcggcgggactaagctgaccgttctgcgccagcctaaagccgctccaa gcgtgaccctgttcccccccagcagcgaggaactgcaggccaacaaagccaccctggtgtgc ctgatcagcgatttctaccccggggccgtgaccgttgcctggaaggccgacagcagccctgt gaaggccggggtggagaccacaaccccctccaagcagagcaacaacaagtacgccgcaagct cctacctgagcctgactcccgagcagtggaaatctcataggtcttacagttgccaggttaca cacgaagggagcacagtggaaaaaacagtggcccccaccgaatgctcctgaExample otelixizumab Fab nucleotide sequence (SEQ ID NO: 140)PolynucleotidesThe present invention provides polynucleotides comprising: (a) a nucleotide sequenceencoding a TNF inhibitor; and / or (b) a nucleotide sequence encoding a CD3 inhibitor.The present invention provides polynucleotides comprising: (a) a nucleotide sequenceencoding a TNF inhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor. Thepresent invention also provides a combination of: (a) a polynucleotide comprising a nucleotide sequence encoding a TNF inhibitor; and (b) a polynucleotide comprising a nucleotide sequence encoding a TNF inhibitor.The present invention also provides polynucleotides comprising a nucleotide sequenceencoding the CD3 inhibitor of the invention.Polynucleotides of the invention may comprise DNA or RNA, preferably DNA. They may be single-stranded or double-stranded. Polynucleotides such as DNA polynucleotides may beproduced recombinantly, synthetically or by any means available to those of skill in the art.They may also be cloned by standard techniques. The polynucleotides may be isolatedpolynucleotides. Longer polynucleotides will generally be produced using recombinant means, for example using polymerase chain reaction (PCR) cloning techniques. This will involve making a pair of primers (e.g. of about 15 to 30 nucleotides) flanking the target sequence which it is desired to clone, bringing the primers into contact with mRNA or cDNA obtained from an animal or humancell, performing a polymerase chain reaction under conditions which bring about amplificationof the desired region, isolating the amplified fragment (e.g. by purifying the reaction mixture with an agarose gel) and recovering the amplified DNA. The primers may be designed to contain suitable restriction enzyme recognition sites so that the amplified DNA can be cloned into a suitable vector. The polynucleotides may be modified by any method available in the art. Such modifications may be carried out in order to enhance the in vivo activity or lifespan of the polynucleotides. VectorsThe present invention provides vectors comprising: (a) a nucleotide sequence encoding a TNFinhibitor; and / or (b) a nucleotide sequence encoding a CD3 inhibitor.The present invention provides vectors comprising: (a) a nucleotide sequence encoding a TNFinhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor. The present invention alsoprovides a combination of: (a) a vector comprising a nucleotide sequence encoding a TNFinhibitor; and (b) a vector comprising a nucleotide sequence encoding a TNF inhibitor.The present invention also provides vectors comprising a nucleotide sequence encoding the CD3 inhibitor of the invention. A vector is a tool that allows or facilitates the transfer of an entity from one environment to another. The four major types of vectors are plasmids, viral vectors, cosmids, and artificial chromosomes. The vectors of the present invention may be capable of transducing ocular cells (e.g. retinal ganglion cells, RPE cells, photoreceptors, glial cells). In some embodiments, the vectors of the present invention are capable of specifically transducing ocular cells.In some embodiments, a vector of the present invention is capable of transducing retinal cells.In some embodiments, a vector of the present invention is capable of specifically transducingretinal cells. The retina is the multi-layered membrane, which lines the inner posterior chamber of the eye and senses an image of the visual world which is communicated to the brain via theoptic nerve. In order from the inside to the outside of the eye, the retina comprises the layersof the neurosensory retina and retinal pigment epithelium, with the choroid lying outside theretinal pigment epithelium.In some embodiments, a vector of the present invention is capable of transducing retinalganglion cells. In some embodiments, a vector of the present invention is capable ofspecifically transducing retinal ganglion cells. A retinal ganglion cell is a type of neuron locatednear the inner surface of the retina of the eye.Suitable vectors for transducing ocular cells include viral vectors such as parvovirus vectors(e.g. AAV vectors), lentivirus vectors, adenovirus vectors and also non-viral delivery systems(see e.g. Rodrigues, G.A., et al., 2019. Pharmaceutical research, 36(2), pp.1-20).A vector of the present invention may be a viral vector. A viral vector of the present invention is preferably an adeno-associated viral (AAV), although it is contemplated that other viral vectors may be used. In some embodiments, the viral vector is any of a parvoviral vector, anadenoviral vector, a herpes simplex viral vector, an anelloviral vector, a retroviral vector, or alentiviral vector.A vector of the present invention may be in the form of a viral vector particle. In someembodiments, the viral vector is any of a parvoviral vector particle, an adenoviral vectorparticle, a herpes simplex viral vector particle, an anelloviral vector particle, a retroviral vectorparticle, or a lentiviral vector particle. Preferably, a viral vector of the present invention is inthe form of an AAV vector particle. Methods of preparing and modifying viral vectors and viral vector particles, such as those derived from AAV, are known in the art. Suitable methods are described in Ayuso, E., et al., 2010. Current gene therapy, 10(6), pp.423-436, Merten, O.W., et al., 2016. Molecular Therapy-Methods & Clinical Development, 3, p.16017; and Nadeau, I. and Kamen, A., 2003. Biotechnology advances, 20(7-8), pp.475-489. Parvovirus vectorsA vector of the present invention may be a parvovirus vector. A vector of the present inventionmay be in the form of a parvovirus vector particle.Parvoviruses, and especially the adeno-associated virus (AAV), provide a versatile platformfor the rational design of human gene-therapy vectors. Typically, parvoviruses are composedof a small, non-enveloped capsid containing a single-stranded DNA genome. Suitably, theparvovirus vector is from the Parvovirinae subfamily, which includes Dependoparvovirus,Protoparvovirus, and Bocaparvovirus. A vector of the present invention may be a hybrid genetherapy vector based on parvoviruses (see e.g. Fakhiri, J. and Grimm, D., 2021. Molecular Therapy, 29(12), pp.3359-3382).In some embodiments, a vector of the present invention is a dependoparvovirus vector. Insome embodiments, a vector of the present invention is in the form of a dependoparvovirusvector. Some dependoparvoviruses are also known as adeno-associated viruses because they cannot replicate productively in their host cell without the cell being co-infected by a helper virus such as an adenovirus. In preferred embodiments, a vector of the present invention is an adeno-associated viral (AAV)vector. In preferred embodiments, a vector of the present invention is in the form of an AAVvector particle.AAV genomes The AAV vector or AAV vector particle may comprise an AAV genome or a fragment orderivative thereof. An AAV genome is a polynucleotide sequence, which may encode functionsneeded for production of an AAV particle. These functions include those operating in the replication and packaging cycle of AAV in a host cell, including encapsidation of the AAV genome into an AAV particle. Naturally occurring AAVs are replication-deficient and rely on the provision of helper functions in trans for completion of a replication and packaging cycle. Accordingly, the AAV genome of the AAV vector of the invention is typically replication- deficient. The AAV genome may be in single-stranded form, either positive or negative-sense, or alternatively in double-stranded form. The use of a double-stranded form allows bypass of the DNA replication step in the target cell and so can accelerate transgene expression.AAVs occurring in nature may be classified according to various biological systems. The AAVgenome may be from any naturally derived serotype, isolate or clade of AAV.AAV may be referred to in terms of their serotype. A serotype corresponds to a variantsubspecies of AAV which, owing to its profile of expression of capsid surface antigens, has a distinctive reactivity which can be used to distinguish it from other variant subspecies. Typically, an AAV vector particle having a particular AAV serotype does not efficiently cross-react with neutralising antibodies specific for any other AAV serotype. AAV serotypes includeAAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10 and AAV11. In someembodiments, the AAV vector of the present invention is an AAV1, AAV2, AAV4, AAV5, AAV6,AAV7, AAV8, or AAV9 serotype, or a variant thereof. In some embodiments, the AAV vector of the present invention is an AAV2 serotype, or a variant thereof. The AAV genome may also comprise packaging genes, such as rep and / or cap genes whichencode packaging functions for an AAV particle. The rep gene encodes one or more of theproteins Rep78, Rep68, Rep52 and Rep40 or variants thereof. The cap gene encodes one or more capsid proteins such as VP1, VP2 and VP3 or variants thereof. These proteins make up the capsid of an AAV particle, which determines the AAV serotype. The AAV genome may be the full genome of a naturally occurring AAV. For example, a vector comprising a full AAV genome may be used to prepare an AAV vector or vector particle. Preferably, the AAV genome is derivatised for the purpose of administration to patients. Such derivatisation is standard in the art and the invention encompasses the use of any known derivative of an AAV genome, and derivatives which could be generated by applyingtechniques known in the art. The AAV genome may be a derivative of any naturally occurringAAV. Suitably, the AAV genome is a derivative of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6,AAV7, AAV8, AAV9, AAV10, or AAV11. Suitably, the AAV genome is a derivative of AAV2. Derivatives of an AAV genome include any truncated or modified forms of an AAV genome which allow for expression of a transgene from an AAV vector of the invention in vivo. Typically, it is possible to truncate the AAV genome significantly to include minimal viral sequence yet retain the above function. This is preferred for safety reasons to reduce the risk of recombination of the vector with wild-type virus, and also to avoid triggering a cellular immune response by the presence of viral gene proteins in the target cell. Typically, a derivative will include at least one inverted terminal repeat sequence (ITR), preferably more than one ITR, such as two ITRs or more. One or more of the ITRs may be derived from AAV genomes having different serotypes, or may be a chimeric or mutant ITR. A preferred mutant ITR is one having a deletion of a trs (terminal resolution site). This deletionallows for continued replication of the genome to generate a single-stranded genome whichcontains both coding and complementary sequences, i.e. a self-complementary AAV genome. This allows for bypass of DNA replication in the target cell, and so enables accelerated transgene expression.The AAV genome may comprise one or more ITR sequences from any naturally derivedserotype, isolate or clade of AAV or a variant thereof. The AAV genome may comprise at leastone, such as two, AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, or AAV11 ITRs, or variants thereof.Suitably, the AAV genome may comprise at least one, such as two, AAV2 ITRs, or variantsthereof. In some embodiments, the AAV genome comprises an AAV25’ ITR and / or an AAV23’ ITR.In some embodiments, the AAV genome comprises a 5’ ITR having at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 141. In some embodiments, theAAV genome comprises a 5’ ITR comprising or consisting of SEQ ID NO: 141.ctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtcgggcgacctttgg tcgcccggcctcagtgagcgagcgagcgcgcagagagggagtggccaactccatcactaggg gttcct Example AAV25’ITR (SEQ ID NO: 141)In some embodiments, the AAV genome comprises a 3’ ITR having at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least98%, at least 99% identity, or 100% identity to SEQ ID NO: 142. In some embodiments, theAAV genome comprises a 3’ ITR comprising or consisting of SEQ ID NO: 142. aggaacccctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggcc gggcgaccaaaggtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgagcgagc gcgcag Example AAV23’ITR (SEQ ID NO: 142) The inclusion of one or more ITRs is preferred to aid concatamer formation of the AAV vector in the nucleus of a host cell, for example following the conversion of single-stranded vector DNA into double-stranded DNA by the action of host cell DNA polymerases. The formation ofsuch episomal concatamers protects the AAV vector during the life of the host cell, therebyallowing for prolonged expression of the transgene in vivo.The one or more ITRs may flank: (a) the nucleotide sequence encoding a TNF inhibitor; and / or(b) the nucleotide sequence encoding a CD3 inhibitor. In some embodiments, the AAVgenome comprises (a) a nucleotide sequence encoding a TNF inhibitor; and (b) a nucleotidesequence encoding a CD3 inhibitor, flanked by one or more ITRs. In some embodiments, theAAV genome comprises (a) a nucleotide sequence encoding a TNF inhibitor; or (b) anucleotide sequence encoding a CD3 inhibitor, flanked by one or more ITRs.Suitably, the AAV genome may comprise one or more AAV2 ITR sequences flanking (a) thenucleotide sequence encoding a TNF inhibitor; and / or (b) the nucleotide sequence encodinga CD3 inhibitor. Suitably, the AAV genome may comprise two AAV2 ITR sequences flankingeither side of (a) the nucleotide sequence encoding a TNF inhibitor; and / or (b) the nucleotidesequence encoding a CD3 inhibitor. In some embodiments, the AAV genome comprises (a) anucleotide sequence encoding a TNF inhibitor; and (b) a nucleotide sequence encoding a CD3inhibitor, flanked by one or more AAV2 ITR sequences. In some embodiments, the AAVgenome comprises two AAV2 ITR sequences flanking either side of (a) a nucleotide sequenceencoding a TNF inhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor. In someembodiments, the AAV genome comprises (a) a nucleotide sequence encoding a TNFinhibitor; or (b) a nucleotide sequence encoding a CD3 inhibitor, flanked by one or more AAV2ITRs. In some embodiments, the AAV genome comprises (a) two AAV2 ITR sequencesflanking either side of a nucleotide sequence encoding a TNF inhibitor; or (b) two AAV2 ITRsequences flanking either side of a nucleotide sequence encoding a CD3 inhibitor.Suitably, ITR elements will be the only sequences retained from the native AAV genome inthe derivative. A derivative will preferably not include the rep and / or cap genes of the nativegenome and any other sequences of the native genome. This is preferred for the reasons described above, and also to reduce the possibility of integration of the vector into the host cell genome. Additionally, reducing the size of the AAV genome allows for increased flexibility in incorporating other sequence elements (such as regulatory elements) within the vector in addition to the transgene. The following portions could therefore be removed in a derivative of the invention: one inverted terminal repeat (ITR) sequence, the replication (rep) and capsid (cap) genes. However,derivatives may additionally include one or more rep and / or cap genes or other viralsequences of an AAV genome. Naturally occurring AAV integrates with a high frequency at a specific site on human chromosome 19, and shows a negligible frequency of random integration, such that retention of an integrative capacity in the AAV vector may be tolerated in a therapeutic setting.The invention additionally encompasses the provision of sequences of an AAV genome ina different order and configuration to that of a native AAV genome. The invention alsoencompasses the replacement of one or more AAV sequences or genes with sequencesfrom another virus or with chimeric genes composed of sequences from more than onevirus. Such chimeric genes may be composed of sequences from two or more related viralproteins of different viral species.AAV capsid proteins The AAV vector particle may be encapsidated by capsid proteins. The serotype may facilitate the transduction of ocular cells (e.g. retinal ganglion cells, RPE cells, photoreceptors, glial cells), for example specific transduction of ocular cells. The AAV vector particle may be an ocular tissue-specific vector particle. The AAV vector particle may be encapsidated by anocular tissue-specific capsid. The AAV vector particle may comprise an ocular tissue-specificcapsid protein. In some embodiments, the AAV vector particle is a retinal-specific vector particle. In some embodiments, the AAV vector particle is encapsidated by a retinal-specific capsid. In some embodiments, the AAV vector particle comprises a retinal-specific capsid protein. In some embodiments, the AAV vector particle is a retinal ganglion-specific vector particle. In some embodiments, the AAV vector particle is encapsidated by a retinal ganglion-specificcapsid. In some embodiments, the AAV vector particle comprises a retinal ganglion-specificcapsid protein.Suitably, the AAV vector particles may be transcapsidated forms wherein an AAV genome orderivative having an ITR of one serotype is packaged in the capsid of a different serotype. TheAAV vector particle also includes mosaic forms wherein a mixture of unmodified capsidproteins from two or more different serotypes makes up the viral capsid. The AAV vector particle also includes chemically modified forms bearing ligands adsorbed to the capsid surface. For example, such ligands may include antibodies for targeting a particular cell surface receptor. Where a derivative comprises capsid proteins i.e. VP1, VP2 and / or VP3, the derivative maybe a chimeric, shuffled or capsid-modified derivative of one or more naturally occurring AAVs.In particular, the invention encompasses the provision of capsid protein sequences from different serotypes, clades, clones, or isolates of AAV within the same vector (i.e. apseudotyped vector). The AAV vector may be in the form of a pseudotyped AAV vectorparticle. Chimeric, shuffled or capsid-modified derivatives will be typically selected to provide one or more desired functionalities for the AAV vector. Thus, these derivatives may display increased efficiency of gene delivery, decreased immunogenicity (humoral or cellular), an altered tropism range and / or improved targeting of retinal cells compared to an AAV vector comprising a naturally occurring AAV genome. Increased efficiency of gene delivery may be effected by improved receptor or co-receptor binding at the cell surface, improved internalisation, improved trafficking within the cell and into the nucleus, improved uncoating of the viral particle and improved conversion of a single-stranded genome to double-stranded form. Increased efficiency may also relate to an altered tropism range or targeting of retinal cells, such that the vector dose is not diluted by administration to tissues where it is not needed. Chimeric capsid proteins include those generated by recombination between two or more capsid coding sequences of naturally occurring AAV serotypes. This may be performed for example by a marker rescue approach in which non-infectious capsid sequences of one serotype are co-transfected with capsid sequences of a different serotype, and directed selection is used to select for capsid sequences having desired properties. The capsid sequences of the different serotypes can be altered by homologous recombination within the cell to produce novel chimeric capsid proteins.For example, a directed evolution approach has been leveraged to generate novel AAVvectors that can more effectively cross biological barriers and target specific cell types. An example is the identification of the AAV.7m8 variant which, following intravitreal injection, is capable of efficient gene delivery to all retina layers in both mice and primates. Similarly, SH10, an AAV6 variant, has increased tropism for glial cells following intravitreal delivery andhas been shown to rescue retinal function in a rat model of RP (see e.g. Rodrigues, G.A., etal., 2019. Pharmaceutical research, 36(2), pp.1-20). Chimeric capsid proteins also include those generated by engineering of capsid protein sequences to transfer specific capsid protein domains, surface loops or specific amino acid residues between two or more capsid proteins, for example between two or more capsid proteins of different serotypes. Shuffled or chimeric capsid proteins may also be generated by DNA shuffling or by error-prone PCR. Hybrid AAV capsid genes can be created by randomly fragmenting the sequences of related AAV genes e.g. those encoding capsid proteins of multiple different serotypes and then subsequently reassembling the fragments in a self-priming polymerase reaction, which may also cause crossovers in regions of sequence homology. A library of hybrid AAV genes created in this way by shuffling the capsid genes of several serotypes can be screened toidentify viral clones having a desired functionality. Similarly, error prone PCR may be used torandomly mutate AAV capsid genes to create a diverse library of variants which may then be selected for a desired property.The sequences of the capsid genes may also be genetically modified to introduce specificdeletions, substitutions or insertions with respect to the native wild-type sequence. In particular, capsid genes may be modified by the insertion of a sequence of an unrelated protein or peptide within an open reading frame of a capsid coding sequence, or at the N-and / or C-terminus of a capsid coding sequence. The unrelated protein or peptide mayadvantageously be one which acts as a ligand for a particular cell type, thereby conferringimproved binding to a target cell or improving the specificity of targeting of the vector to aparticular cell population. The unrelated protein may also be one which assists purification of the viral particle as part of the production process, i.e. an epitope or affinity tag. The site of insertion will typically be selected so as not to interfere with other functions of the viral particle e.g. internalisation, trafficking of the viral particle. For example, AAV variants gave been generated by site-directed mutagenesis of surface- exposed tyrosine residues, which prevents capsid phosphorylation and subsequent ubiquitination and proteasome-mediated degradation. AAV2, AAV8, and AAV9 carrying thesemutations have been shown to have increased transduction efficiency both in vitro and in vivo(see e.g. Petrs-Silva, H., et al., 2009. Molecular therapy, 17(3), pp.463-471).The capsid protein may be an artificial capsid protein. The term “artificial capsid” as usedherein means that the capsid particle comprises an amino acid sequence which does not occur in nature or which comprises an amino acid sequence which has been engineered (e.g.modified) from a naturally occurring capsid amino acid sequence. In other words, the artificialcapsid protein comprises a mutation or a variation in the amino acid sequence compared to the sequence of the parent capsid from which it is derived where the artificial capsid amino acid sequence and the parent capsid amino acid sequences are aligned. The capsid protein may comprise a mutation or modification relative to the wild type capsidprotein which improves the ability to transduce ocular cells relative to an unmodified or wildtype viral particle. Improved ability to transduce ocular cells may be measured for example bymeasuring the expression of a transgene, e.g. GFP, carried by the AAV vector particle,wherein expression of the transgene in ocular cells correlates with the ability of the AAV vectorparticle to transduce ocular cells.Suitably, the AAV vector particle of the present invention is an AAV1, AAV2, AAV4, AAV5,AAV6, AAV7, AAV8, or AAV9 vector particle, or a variant thereof. AAV vector particles with these serotypes can transduce ocular cells. The AAV vector particle of the present invention may comprise AAV1, AAV2, AAV4, AAV5,AAV6, AAV7, AAV8, or AAV9 capsid proteins, or variants thereof. Suitably, the AAV vectorparticle may comprise AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, or AAV9 capsid proteins VP1, VP2 and VP3, or variants thereof. In one embodiment, the AAV vector particle comprises one or more AAV2 ITR sequencesflanking (a) the nucleotide sequence encoding a TNF inhibitor; and / or (b) the nucleotidesequence encoding a CD3 inhibitor and AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, orAAV9 capsid proteins, or variants thereof. In one embodiment, the AAV vector particle comprises an AAV2 genome and AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, or AAV9 capsid proteins, or variants thereof. AAV2 vectors and variants thereof In some embodiments, the AAV vector particle is an AAV2 vector particle, or a variant thereof.In some embodiments, the AAV vector particle comprises AAV2 capsid proteins, or variantsthereof. Suitably, the AAV vector particle may comprise AAV2 capsid protein VP1, VP2 andVP3, or variants thereof. AAV2 variants include AAV2.tYF, AAV2.7m8, R100, AAV2.GL, AAV2.NN, LSV1, R195-003, and dyno-86m. In some embodiments, the AAV vector particle is an AAV2 vector particle, anAAV2.tYF vector particle, an AAV2.7m8 vector particle, a R100 vector particle, an AAV2.GLvector particle, an AAV2.NN vector particle, an LSV1 vector particle, an R195-003 vectorparticle, or a dyno-86m vector particle. In some embodiments, the AAV vector particlecomprises AAV2 capsid proteins, AAV2.tYF capsid proteins, AAV2.7m8 capsid proteins, R100capsid proteins, AAV2.GL capsid proteins, AAV2.NN capsid proteins, LSV1 capsid proteins, R195-003 capsid proteins, or dyno-86m capsid proteins. Suitably, the AAV vector particle maycomprise AAV2 capsid protein VP1, VP2 and VP3, AAV2.tYF capsid protein VP1, VP2 andVP3, AAV2.7m8 capsid protein VP1, VP2 and VP3, R100 capsid protein VP1, VP2 and VP3,AAV2.GL capsid protein VP1, VP2 and VP3, AAV2.NN capsid protein VP1, VP2 and VP3,LSV1 capsid protein VP1, VP2 and VP3, R195-003 capsid protein VP1, VP2 and VP3, or dyno-86m capsid protein VP1, VP2 and VP3.In some embodiments, the AAV vector particle is an AAV2 vector particle, an AAV2.tYF vectorparticle, an AAV2.7m8 vector particle, a R100 vector particle, an AAV2.GL vector particle, oran AAV2.NN vector particle. In some embodiments, the AAV vector particle comprises AAV2capsid proteins, AAV2.tYF capsid proteins, AAV2.7m8 capsid proteins, R100 capsid proteins,AAV2.GL capsid proteins, or AAV2.NN capsid proteins. Suitably, the AAV vector particle maycomprise AAV2 capsid protein VP1, VP2 and VP3, AAV2.tYF capsid protein VP1, VP2 andVP3, AAV2.7m8 capsid protein VP1, VP2 and VP3, R100 capsid protein VP1, VP2 and VP3,AAV2.GL capsid protein VP1, VP2 and VP3, or AAV2.NN capsid protein VP1, VP2 and VP3.In some embodiments, the AAV vector particle is an AAV2 vector particle. In some embodiments, the AAV vector particle comprises AAV2 capsid proteins. In some embodiments, the AAV vector particle comprises AAV2 capsid protein VP1, VP2 and VP3. Suitably, an AAV2 VP1 capsid protein may comprise or consist of the amino acid sequence SEQ ID NO: 143, or a variant which is at least 90% identical to SEQ ID NO: 143. Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identicalto SEQ ID NO: 143. Suitably, an AAV2 VP2 and VP3 capsid protein may be an N-terminaltruncation of SEQ ID NO: 143, or an N-terminal truncation of a variant which is at least 90%identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 143. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNRQAATADVNTQGVLPGMVWQDRDVYLQGPIWAK IPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFITQYSTGQVSVEI EWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLTRNL Example AAV2 VP1 capsid protein (SEQ ID NO: 143)In some embodiments, the AAV vector particle is an AAV2.tYF vector particle. In someembodiments, the AAV vector particle comprises AAV2.tYF capsid proteins. In someembodiments, the AAV vector particle comprises AAV2.tYF capsid protein VP1, VP2 and VP3.Single phenylalanine (F) for tyrosine (Y) substitutions had increased the potency of AAV2following intraocular injection (see e.g. Petrs-Silva, H., et al., 2009. Molecular therapy, 17(3),pp.463-471).Suitably, an AAV2.tYF VP1 capsid protein may comprise or consist of the amino acidsequence SEQ ID NO: 144, or a variant which is at least 90% identical to SEQ ID NO: 144. Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least99% identical to SEQ ID NO: 144. Suitably, an AAV2.tYF VP2 and VP3 capsid protein maybe an N-terminal truncation of SEQ ID NO: 144, or an N-terminal truncation of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 144. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYFLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEFSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNRQAATADVNTQGVLPGMVWQDRDVYLQGPIWAK IPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFITQYSTGQVSVEI EWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRFLTRNL Example AAV2.tYF VP1 capsid protein (SEQ ID NO: 144)In some embodiments, the AAV vector particle is an AAV2.7m8 vector particle. In someembodiments, the AAV vector particle comprises AAV2.7m8 capsid proteins. In some embodiments, the AAV vector particle comprises AAV2.7m8 capsid protein VP1, VP2 and VP3. AAV2.7m8 is an engineered capsid with a 10-amino acid insertion in adeno-associated virus (AAV) surface variable region VIII (VR-VIII) resulting in the ability to efficiently transduce retina cells following intravitreal administration (see e.g. Bennett, A., et al., 2020. Journal of structural biology, 209(2), p.107433). Suitably, an AAV2.7m8 VP1 capsid protein may comprise or consist of the amino acid sequence SEQ ID NO: 145, or a variant which is at least 90% identical to SEQ ID NO: 145. Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least99% identical to SEQ ID NO: 145. Suitably, an AAV2.7m8 VP2 and VP3 capsid protein maybe an N-terminal truncation of SEQ ID NO: 145, or an N-terminal truncation of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 145. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNLALGETTRPARQAATADVNTQGVLPGMVWQDRD VYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFITQ YSTGQVSVEIEWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLTRN L Example AAV2.7m8 VP1 capsid protein (SEQ ID NO: 145) In some embodiments, the AAV vector particle is a R100 vector particle. In some embodiments, the AAV vector particle comprises R100 capsid proteins. In some embodiments, the AAV vector particle comprises R100 capsid protein VP1, VP2 and VP3.R100 demonstrated superior transduction of human retinal cells compared to wild-type AAV(see e.g. Kotterman, M., et al., 2021. bioRxiv 2021.06.24.449775).Suitably, a R100 VP1 capsid protein may comprise or consist of the amino acid sequenceSEQ ID NO: 146, or a variant which is at least 90% identical to SEQ ID NO: 146. Suitably, thevariant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identicalto SEQ ID NO: 146. Suitably, a R100 and VP3 capsid protein may be an N-terminal truncationof SEQ ID NO: 146, or an N-terminal truncation of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 146. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNLAISDQTKHARQAATADVNTQGVLPGMVWQDRD VYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFITQ YSTGQVSVEIEWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLTRN L Example R100 VP1 capsid protein (SEQ ID NO: 146) In some embodiments, the AAV vector particle is an AAV2.GL vector particle. In some embodiments, the AAV vector particle comprises AAV2.GL capsid proteins. In some embodiments, the AAV vector particle comprises AAV2.GL capsid protein VP1, VP2 and VP3.In some embodiments, the AAV vector particle is an AAV2.NN vector particle. In someembodiments, the AAV vector particle comprises AAV2.NN capsid proteins. In some embodiments, the AAV vector particle comprises AAV2.NN capsid protein VP1, VP2 and VP3. AAV2.GL and AAV2.NN mediate widespread and high-level retinal transduction after intravitreal injection in mice, dogs and non-human primates (see e.g. Pavlou, M., et al., 2021. EMBO molecular medicine, 13(4), p.e13392).Suitably, an AAV2.GL VP1 capsid protein may comprise or consist of the amino acid sequenceSEQ ID NO: 147, or a variant which is at least 90% identical to SEQ ID NO: 147. Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identicalto SEQ ID NO: 147. Suitably, an AAV2.GL VP2 and VP3 capsid protein may be an N-terminaltruncation of SEQ ID NO: 147, or an N-terminal truncation of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 147. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNAAAGLSPPTRAARQAATADVNTQGVLPGMVWQD RDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFI TQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLT RNL Example AAV2.GL VP1 capsid protein (SEQ ID NO: 147)Suitably, an AAV2.NN VP1 capsid protein may comprise or consist of the amino acidsequence SEQ ID NO: 148, or a variant which is at least 90% identical to SEQ ID NO: 148. Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least99% identical to SEQ ID NO: 148. Suitably, an AAV2.NN VP2 and VP3 capsid protein may bean N-terminal truncation of SEQ ID NO: 148, or an N-terminal truncation of a variant which isat least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%identical to SEQ ID NO: 148. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNAAANNPTPSRAARQAATADVNTQGVLPGMVWQD RDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFI TQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLT RNL Example AAV2.NN VP1 capsid protein (SEQ ID NO: 148) In some embodiments, the AAV vector particle is a LSV1 vector particle. In some embodiments, the AAV vector particle comprises LSV1 capsid proteins. In someembodiments, the AAV vector particle comprises LSV1 capsid protein VP1, VP2 and VP3.Loop swap variant 1 (LSV1) transduces the retina and retinal pigment epithelium (RPE) fromthe vitreous and is based on AAV2.5T, a substitution from aa 571-579 (see e.g. Baker, C.K.,et al., 2022, Molecular Therapy, 30(4), p.575). Suitably, a LSV1 VP1 capsid protein may comprise or consist of the amino acid sequenceSEQ ID NO: 149 or a variant which is at least 90% identical to SEQ ID NO: 149 Suitably, thevariant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identicalto SEQ ID NO: 149 Suitably, a LSV1 VP2 and VP3 capsid protein may be an N-terminaltruncation of SEQ ID NO: 149 or an N-terminal truncation of a variant which is at least 90%identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 149 MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPFGLVEEGAKTAPTGKRIDDHFPKRKKARTEEDSKPSTSSDAEAGPSGSQQLQIPAQPA SSLGADTMSAGGGGPLGDNNQGADGVGNASGDWHCDSTWMGDRVVTKSTRTWVLPSYNNHQY REIKSGSVDGSNANAYFGYSTPWGYFDFNRFHSHWSPRDWQRLINNYWGFRPRSLRVKIFNI QVKEVTVQDSTTTIANNLTSTVQVFTDDDYQLPYVVGNGTEGCLPAFPPQVFTLPQYGYATL NRDNTENPTERSSFFCLEYFPSKMLRTGNNFEFTYNFEEVPFHSSFAPSQNLFKLANPLVDQ YLYRFVSTNNTGGVQFNKNLAGRYANTYKNWFPGPMGRTQGWNLGSGVNRASVSAFATTNRM ELEGASYQVPPQPNGMTNNLQGSNTYALENTMIFNSQPANPGTTATYLEGNMLITSESETQP VNRVAYNVGGQMLAHKFKSGDAPTTGTYNLQEIVPGSVWMERDVYLQGPIWAKIPETGAHFH PSPAMGGFGLKHPPPMMLIKNTPVPGNITSFSDVPVSSFITQYSTGQVTVEMEWELKKENSK RWNPEIQYTNNYNDPQFVDFAPDSTGEYRTTRPIGTRYLTRPL Example LSV1 capsid protein (SEQ ID NO: 149) In some embodiments, the AAV vector particle is a R195-003 vector particle. In some embodiments, the AAV vector particle comprises R195-003 capsid proteins. In some embodiments, the AAV vector particle comprises R195-003 capsid protein VP1, VP2 and VP3 (see e.g. Human Gene Therapy Methods 2022; 33 (23-24): A27-A28). In some embodiments, the AAV vector particle is a dyno-86m vector particle. In some embodiments, the AAV vector particle comprises dyno-86m capsid proteins. In some embodiments, the AAV vector particle comprises dyno-86m capsid protein VP1, VP2 and VP3 (see e.g. Molecular Therapy 2023; 31(4), S1, p.1284). In some embodiments, the AAV vector particle comprises one or more AAV2 ITR sequencesflanking (a) the nucleotide sequence encoding a TNF inhibitor; and / or (b) the nucleotidesequence encoding a CD3 inhibitor and AAV2 capsid proteins, or variants thereof. In someembodiments, the AAV vector particle comprises an AAV2 genome and AAV2 capsid proteins, or variants thereof. Other parvovirus vectorsIn some embodiments, a vector of the present invention is a protoparvovirus vector. In someembodiments, a vector of the present invention is in the form of a protoparvovirus vector.Protoparvoviruses have been studied extensively and utilized as vectors, including the minutevirus of mice (MVM), the rat parvovirus H1, and the LuIII virus. Human variants that have beenfound recently include bufavirus (BuV), tusavirus (TuV), and cutavirus (CuV) (see e.g. Fakhiri,J. and Grimm, D., 2021. Molecular Therapy, 29(12), pp.3359-3382).In some embodiments, a vector of the present invention is a bocaparvovirus vector. In someembodiments, a vector of the present invention is in the form of a bocaparvovirus vector. Theuse of Human bocavirus 1 (HBoV1) as a parvoviral vector for gene delivery has beendescribed (see e.g. Shao, L., et al., 2021. Frontiers in Microbiology, 12, p.1463).Other viral vectorsRetroviral and lentiviral vectorsA vector of the present invention may be a retroviral vector or a lentiviral vector. TAhe vectorof the present invention may be a retroviral vector particle or a lentiviral vector particle.A retroviral vector may be derived from or may be derivable from any suitable retrovirus. A large number of different retroviruses have been identified. Examples include murine leukaemia virus (MLV), human T-cell leukaemia virus (HTLV), mouse mammary tumour virus (MMTV), Rous sarcoma virus (RSV), Fujinami sarcoma virus (FuSV), Moloney murine leukaemia virus (Mo-MLV), FBR murine osteosarcoma virus (FBR MSV), Moloney murine sarcoma virus (Mo-MSV), Abelson murine leukaemia virus (A-MLV), avian myelocytomatosis virus-29 (MC29) and avian erythroblastosis virus (AEV). Retroviruses may be broadly divided into two categories, “simple” and “complex”. Retroviruses may be even further divided into seven groups. Five of these groups represent retroviruses with oncogenic potential. The remaining two groups are the lentiviruses and the spumaviruses. The basic structure of retrovirus and lentivirus genomes share many common features such as a 5’ LTR and a 3’ LTR. Between or within these are located a packaging signal to enable the genome to be packaged, a primer binding site, integration sites to enable integration intoa host cell genome, and gag, pol and env genes encoding the packaging components – theseare polypeptides required for the assembly of viral particles. Lentiviruses have additional features, such as rev and RRE sequences in HIV, which enable the efficient export of RNA transcripts of the integrated provirus from the nucleus to the cytoplasm of an infected target cell. In the provirus, these genes are flanked at both ends by regions called long terminal repeats (LTRs). The LTRs are responsible for proviral integration and transcription. LTRs also serve as enhancer-promoter sequences and can control the expression of the viral genes. The LTRs themselves are identical sequences that can be divided into three elements: U3, R and U5. U3 is derived from the sequence unique to the 3’ end of the RNA. R is derived from a sequence repeated at both ends of the RNA. U5 is derived from the sequence unique to the 5’ end of the RNA. The sizes of the three elements can vary considerably among different retroviruses. In a defective retroviral vector genome gag, pol and env may be absent or not functional. In a typical retroviral vector, at least part of one or more protein coding regions essential for replication may be removed from the virus. This makes the viral vector replication-defective. Portions of the viral genome may also be replaced by a library encoding candidate modulating moieties operably linked to a regulatory control region and a reporter moiety in the vector genome in order to generate a vector comprising candidate modulating moieties which is capable of transducing a target host cell and / or integrating its genome into a host genome.Lentivirus vectors are part of the larger group of retroviral vectors. In brief, lentiviruses can bedivided into primate and non-primate groups. Examples of primate lentiviruses include but are not limited to human immunodeficiency virus (HIV), the causative agent of human acquired immunodeficiency syndrome (AIDS); and simian immunodeficiency virus (SIV). Examples of non-primate lentiviruses include the prototype “slow virus” visna / maedi virus (VMV), as well as the related caprine arthritis-encephalitis virus (CAEV), equine infectious anaemia virus (EIAV), and the more recently described feline immunodeficiency virus (FIV) and bovine immunodeficiency virus (BIV). The lentivirus family differs from retroviruses in that lentiviruses have the capability to infectboth dividing and non-dividing cells. In contrast, other retroviruses, such as MLV, are unableto infect non-dividing or slowly dividing cells such as those that make up, for example, muscle, brain, lung and liver tissue.A lentiviral vector, as used herein, is a vector which comprises at least one component partderivable from a lentivirus. Preferably, that component part is involved in the biological mechanisms by which the vector infects cells, expresses genes or is replicated. The lentiviral vector may be a “primate” vector. The lentiviral vector may be a “non-primate” vector (i.e. derived from a virus which does not primarily infect primates, especially humans). Examples of non-primate...

Claims

CLAIMS1. A vector comprising: (a) a nucleotide sequence encoding a TNF inhibitor; and (b) anucleotide sequence encoding a CD3 inhibitor.

2. The vector according to any preceding claim, wherein the nucleotide sequence encoding a TNF inhibitor is linked to the nucleotide sequence encoding a CD3 inhibitor by a nucleotidesequence encoding a 2A self-cleaving peptide, an enzymatically cleavable peptide motif,and / or an IRES element.

3. The vector according to any preceding claim, wherein the nucleotide sequence encoding a TNF inhibitor is linked to the nucleotide sequence encoding a CD3 inhibitor by a nucleotide sequence encoding a 2A self-cleaving peptide.

4. The vector according to any preceding claim, wherein the nucleotide sequence encoding aTNF inhibitor and the nucleotide sequence encoding a CD3 inhibitor are each operably linkedto the same promoter.

5. The vector according to any preceding claim, wherein the vector comprises a nucleotide sequence comprising or consisting of from 5’ to 3’: a promoter; the nucleotide sequenceencoding a TNF inhibitor; a 2A self-cleaving peptide, an enzymatically cleavable peptide motif,and / or an IRES element; and the nucleotide sequence encoding a CD3 inhibitor.

6. The vector according to any of claims 1-5, wherein the vector comprises a nucleotidesequence comprising or consisting of from 5’ to 3’: a promoter; the nucleotide sequenceencoding a CD3 inhibitor; a 2A self-cleaving peptide, an enzymatically cleavable peptide motif,and / or an IRES element; and the nucleotide sequence encoding a TNF inhibitor.

7. A kit comprising: (a) a vector comprising a nucleotide sequence encoding a TNF inhibitor;and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.

8. A pharmaceutical composition comprising: (a) a vector comprising a nucleotide sequenceencoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3inhibitor.

9. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe TNF inhibitor is any of adalimumab or a fragment thereof, infliximab or a fragment thereof,golimumab or a fragment thereof, or certolizumab or a fragment thereof.

10. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe TNF inhibitor is adalimumab or a fragment thereof, or infliximab or a fragment thereof,preferably wherein the TNF inhibitor is adalimumab or a fragment thereof.

11. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe TNF inhibitor is an antigen binding fragment (Fab) of adalimumab.

12. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe TNF inhibitor is an anti-TNF antibody or fragment thereof comprising one or more CDRregions selected from SEQ ID NOs: 16 to 21 or derivatives thereof comprising one amino acidsubstitution, preferably wherein the TNF inhibitor is an anti-TNF antibody or fragment thereofcomprising CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 comprising orconsisting of SEQ ID NOs: 16, 17, 18, 19, 20 and 21 respectively or derivatives thereofcomprising one amino acid substitution.

13. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe TNF inhibitor is an anti-TNF antibody or fragment thereof comprising a heavy chaincomprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 22 and / or alight chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:

23.

14. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe CD3 inhibitor is any of foralumab or a fragment thereof, teplizumab or a fragment thereof,visilizumab or a fragment thereof, otelixizumab or a fragment thereof, muromonab-CD3 or afragment thereof, T3 / 4.A or a fragment thereof, YTH12.5 or a fragment thereof, or HuM291 ora fragment thereof.

15. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe CD3 inhibitor is foralumab or a fragment thereof, teplizumab or a fragment thereof,visilizumab or a fragment thereof, or otelixizumab or a fragment thereof.

16. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe CD3 inhibitor is an antigen binding fragment (Fab) of foralumab, teplizumab, visilizumab,or otelixizumab.

17. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe CD3 inhibitor is an anti-CD3 antibody or fragment thereof comprising one or more CDRregions selected from: (a) SEQ ID NOs: 70 to 75 or derivatives thereof comprising one aminoacid substitution, (b) SEQ ID NOs: 81 to 86 or derivatives thereof comprising one amino acidsubstitution, (c) SEQ ID NOs: 92 to 97 or derivatives thereof comprising one amino acidsubstitution, and (d) SEQ ID NOs: 103 to 108 or derivatives thereof comprising one aminoacid substitution, preferably wherein the CD3 inhibitor is an anti-CD3 antibody or fragmentthereof comprising (a) CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3comprising or consisting of SEQ ID NOs: 70, 71, 72, 73, 74 and 75 respectively or derivativesthereof comprising one amino acid substitution; (b) CDR regions HCDR1, HCDR2, HCDR3,LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs: 81, 82, 83, 84, 85 and 86respectively or derivatives thereof comprising one amino acid substitution; (c) CDR regionsHCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs:92, 93, 94, 95, 96 and 97 respectively or derivatives thereof comprising one amino acidsubstitution; or (d) CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3comprising or consisting of SEQ ID NOs: 103, 104, 105, 106, 107 and 108 respectively orderivatives thereof comprising one amino acid substitution.

18. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe CD3 inhibitor is an anti-CD3 antibody or fragment thereof comprising: (a) a heavy chaincomprising or consisting of a sequence with at least 70% identity to SEQ ID NO: 76 and / or alight chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:77; (b) a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQID NO: 87 and / or a light chain comprising or consisting of a sequence with at least 70% identityto SEQ ID NO: 88; (c) a heavy chain comprising or consisting of a sequence with at least 70%identity to SEQ ID NO: 98 and / or a light chain comprising or consisting of a sequence with atleast 70% identity to SEQ ID NO: 99; or (d) a heavy chain comprising or consisting of asequence with at least 70% identity to SEQ ID NO: 109 and / or a light chain comprising orconsisting of a sequence with at least 70% identity to SEQ ID NO:

110.

19. The vector, kit, or pharmaceutical composition according to any preceding claim, wherein the nucleotide sequence encoding a TNF inhibitor is operably linked to an inflammation-inducible promoter and / or the nucleotide sequence encoding a CD3 inhibitor is operably linkedto an inflammation-inducible promoter.

20. The vector, kit, or pharmaceutical composition according to claim 19, wherein the inflammation-inducible promoter comprises one or more inflammation-inducible transcription factor binding motif selected from: an AP-1 transcription factor binding motif; a NF-κB transcription factor binding motif; an IRF transcription factor binding motif; a STAT transcription factor binding motif; and a NFAT transcription factor binding motif or any combination thereof.

21. The vector, kit, or pharmaceutical composition according to claim 19 or 20, wherein the inflammation-inducible promoter comprises one or more AP-1 binding motif and / or one or more NF-κB binding motif.

22. The vector, kit, or pharmaceutical composition according to any of claims 19-21, whereinthe inflammation-inducible promoter comprises two or more AP-1 binding motifs and / or two ormore NF-κB binding motifs, three or more AP-1 binding motifs and / or three or more NF-κB binding motifs, four or more AP-1 binding motifs and / or four or more NF-κB binding motifs, or five or more AP-1 binding motifs and / or five or more NF-κB binding motifs 23. The vector, kit, or pharmaceutical composition according to any of claims 19-22, wherein the inflammation-inducible promoter comprises at least one AP-1 binding motif coupled to at least one NF-κB binding motif.

24. The vector, kit, or pharmaceutical composition according to any of claims 19-23, wherein the inflammation-inducible promoter comprises five AP-1 binding motifs coupled to five NF-κB binding motifs.

25. The vector, kit, or pharmaceutical composition according to any of claims 20-24, wherein the AP-1 binding motif comprises or consists of SEQ ID NO: 151, or wherein the AP-1 bindingmotif comprises or consists of any of SEQ ID NOs: 152-154 or derivatives thereof comprisingone nucleotide substitution.

26. The vector, kit, or pharmaceutical composition according to any of claims 20-25, wherein the NF-κB binding motif comprises or consists of SEQ ID NO: 155, or wherein the NF-κBbinding motif comprises or consists of SEQ ID NO: 156 or a derivative thereof comprising twoor fewer nucleotide substitutions.

27. The vector, kit, or pharmaceutical composition according to any of claims 19-26, wherein the inflammation-inducible promoter comprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO:

157.

28. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe vector(s) further comprise a polyadenylation sequence.

29. The vector, kit, or pharmaceutical composition according to claim 28, wherein the polyadenylation sequence is selected from any of: a bovine growth hormone (bGH) polyadenylation sequence, a SV40 polyadenylation sequence, and a rabbit beta-globin polyadenylation sequence.

30. The vector, kit, or pharmaceutical composition according to claim 28 or 29, wherein the polyadenylation sequence comprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO:

163.

31. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe vector(s) further comprise a woodchuck hepatitis post-transcriptional regulatory element(WPRE).

32. The vector, kit, or pharmaceutical composition according to claim 31, wherein the WPRE comprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO:

164.

33. The vector, kit, or pharmaceutical composition according to any preceding claim, whereinthe vector(s) further comprise an intron, optionally wherein the intron is selected from a beta-globin intron or a SV40 intron.

34. The vector, kit, or pharmaceutical composition according to claim 33, wherein the intron comprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO:

165.

35. The vector, kit, or pharmaceutical composition according to any previous claim, whereinthe vector(s) are a viral vector, optionally wherein the vector(s) are any of a parvoviral vector,an adenoviral vector, a herpes simplex viral vector, an anelloviral vector, a retroviral vector or a lentiviral vector.

36. The vector, kit, or pharmaceutical composition according to any previous claim, whereinthe vector(s) are an adeno-associated virus (AAV) vector.

37. The vector, kit, or pharmaceutical composition according to any previous claim, whereinthe vector(s) are an AAV vector particle.

38. The vector, kit, or pharmaceutical composition according to claim 37, wherein the AAV vector particle is pseudotyped to confer ocular tissue tropism.

39. The vector, kit, or pharmaceutical composition according to claim 37 or 38, wherein theAAV vector particle comprises AAV2 capsid proteins or AAV2 capsid variant proteins, optionally wherein the AAV2 capsid variant is selected from any of: AAV2.tYF, AAV2.7m8, R100, AAV2.GL and AAV2.NN.

40. The vector, kit, or pharmaceutical composition according to any previous claim, whereinthe vector(s) comprise one or more inverted terminal repeats (ITRs).

41. An isolated cell comprising: (i) the vector according to any of claims 1-6 or 9-40; and / or(ii) (a) a vector comprising a nucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.

42. A kit for the production of: (i) the vector of any one of claims 1-6 or 9-40; and / or(ii) (a) a vector comprising a nucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.

43. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluentor excipient in combination with:(i) the vector according to any one of claims 1-6 or 9-40;(ii) (a) a vector comprising a nucleotide sequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor; and / or(iii) the isolated cell according to claim 41.

44. A vector according to any one of claims 1-6 or 9-40, an isolated cell according to claim 41, and / or a pharmaceutical composition according to claim 43, for use as a medicament.

45. Use of a vector according to any one of claims 1-6 or 9-40, an isolated cell according to claim 41, or a pharmaceutical composition according to claim 43, for the manufacture of a medicament.

46. A method comprising administering a vector according to any one of claims 1-6 or 9-40, an isolated cell according to claim 41, or a pharmaceutical composition according to claim 43, to a subject in need thereof.

47. A vector for use in preventing or treating an inflammatory eye disease, wherein the vectorcomprises: (a) a nucleotide sequence encoding a TNF inhibitor; and (b) a nucleotide sequenceencoding a CD3 inhibitor.

48. Use of a vector in the manufacture of a medicament for preventing or treating aninflammatory eye disease, wherein the vector comprises: (a) a nucleotide sequence encodinga TNF inhibitor; and (b) a nucleotide sequence encoding a CD3 inhibitor.

49. A method for preventing or treating an inflammatory eye disease, wherein the method comprises administering a vector to a subject in need thereof, wherein the vector comprises:(a) a nucleotide sequence encoding a TNF inhibitor; and (b) a nucleotide sequence encodinga CD3 inhibitor.

50. A product comprising: (a) a vector comprising a nucleotide sequence encoding a TNFinhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor, as acombined preparation for simultaneous, separate or sequential use in preventing or treatingan inflammatory eye disease.

51. A method for preventing or treating an inflammatory eye disease, wherein the methodcomprises administering to a subject in need thereof: (a) a vector comprising a nucleotidesequence encoding a TNF inhibitor; and (b) a vector comprising a nucleotide sequence encoding a CD3 inhibitor.

52. A vector according to any one of claims 1-6 or 9-40, or a pharmaceutical composition according to claim 43, for use in preventing or treating an inflammatory eye disease.

53. Use of a vector according to any one of claims 1-6 or 9-40, or a pharmaceutical composition according to claim 43, for the manufacture of a medicament for preventing or treating an inflammatory eye disease.

54. A method of preventing or treating an inflammatory eye disease comprising administering a vector according to any one of claims 1-6 or 7-40, or a pharmaceutical composition according to claim 43, to a subject in need thereof.

55. The vector or pharmaceutical composition for use according to claim 47 or 52, the useaccording to claim 48 or 53, the method according to claim 49, 51 or 54, or the product for useaccording to claim 50, wherein the inflammatory eye disease is uveitis.

56. The vector or pharmaceutical composition for use according to any of claims 47, 52 or 55, the use according to any of claims 48, 53 or 55, the method according to any of claims 49, 51or 54-55, or the product for use according to claim 50 or 55, wherein the vector(s) orpharmaceutical composition are administered intraocularly.

57. The vector or pharmaceutical composition for use according to any of claims 47, 52, or 55-56, the use according to any of claims 48, 53 or 55-56, the method according to any ofclaims 49, 51 or 54-56, or the product for use according to any of claims 50 or 55-56, whereinthe vector(s) or pharmaceutical composition are administered via intravitreal, subretinal,subconjunctival, sub-Tenon’s or suprachoroidal injection.

58. The vector or pharmaceutical composition for use according to any of claims 47, 52, or 55-57, the use according to any of claims 48, 53 or 55-57, the method according to any ofclaims 49, 51 or 54-57, or the product for use according to any of claims 50 or 55-57, whereinthe vector(s) or pharmaceutical composition are administered via intravitreal injection.

59. The vector or pharmaceutical composition for use according to any of claims 47, 52, or 55-58, the use according to any of claims 48, 53 or 55-58, the method according to any of claims 49, 51 or 54-58, or the product for use according to any of claims 50 or 55-58, whereinthe vector(s) or pharmaceutical composition are administered as a single dose.

60. The vector or pharmaceutical composition for use according to any of claims 47, 52, or55-59, the use according to any of claims 48, 53 or 55-59, the method according to any of claims 49, 51 or 54-59, or the product for use according to any of claims 50 or 55-59, whereinthe vector(s) are administered at a dose of at least about 1E10 vg / mL, at least about 1E11vg / mL, at least about 1E12 vg / mL, or at least about 5E12 vg / mL.

61. The vector or pharmaceutical composition for use according to any of claims 47, 52, or 55-60, the use according to any of claims 48, 53 or 55-60, the method according to any of claims 49, 51 or 54-60, or the product for use according to any of claims 50 or 55-60, whereinthe vector(s) are administered at a dose of at least about 1E9 vg / eye, at least about 1E10vg / eye, or at least about 1E11 vg / eye, preferably wherein the vector(s) are administered at adose of about 1E9 vg / eye to about 5E12 vg / eye.

62. The vector or pharmaceutical composition for use according to any of claims 47, 52, or 55-61, the use according to any of claims 48, 53 or 55-61, the method according to any of claims 49, 51 or 54-61, or the product for use according to any of claims 50 or 55-61, whereinthe vector(s) or pharmaceutical composition are administered in response to relapse of aninflammatory eye disease, preferably wherein the inflammatory eye disease is uveitis.

63. A kit comprising: (a) a TNF inhibitor, or a polynucleotide comprising a nucleotide sequenceencoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotidesequence encoding the same.

64. A pharmaceutical composition comprising: (a) a TNF inhibitor, or a polynucleotidecomprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or apolynucleotide comprising a nucleotide sequence encoding the same.

65. A product comprising: (a) a TNF inhibitor, or a polynucleotide comprising a nucleotidesequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising anucleotide sequence encoding the same, as a combined preparation for simultaneous, separate or sequential use in therapy.

66. A product comprising: (a) a TNF inhibitor, or a polynucleotide comprising a nucleotidesequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising anucleotide sequence encoding the same, as a combined preparation for simultaneous, separate or sequential use in preventing or treating an inflammatory eye disease.

67. A method for preventing or treating an inflammatory eye disease, wherein the methodcomprises administering to a subject in need thereof: (a) a TNF inhibitor, or a polynucleotidecomprising a nucleotide sequence encoding the same; and (b) a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same.

68. The product for use according to claim 66 or the method according to claim 67, wherein the inflammatory eye disease is uveitis.

69. The product for use according to claim 66 or 68 or the method according to claim 67 or68, wherein (a) the TNF inhibitor or polynucleotide is administered intraocularly; and / or (b) theCD3 inhibitor or polynucleotide is administered intraocularly.

70. The product for use according to any of claims 66 or 68-69 or the method according to anyof claims 67-69, wherein (a) the TNF inhibitor or polynucleotide is administered via intravitreal,subretinal, subconjunctival, sub-Tenon’s or suprachoroidal injection; and / or (b) the CD3 inhibitor or polynucleotide is administered via intravitreal, subretinal, subconjunctival, sub- Tenon’s or suprachoroidal injection.

71. The product for use according to any of claims 66 or 68-70 or the method according to anyof claims 67-70, wherein (a) the TNF inhibitor or polynucleotide is administered via intravitrealinjection; and / or (b) the CD3 inhibitor or polynucleotide is administered via intravitreal injection.

72. The product for use according to any of claims 66 or 68-71 or the method according to anyof claims 67-71, wherein (a) the TNF inhibitor or polynucleotide is administered in response torelapse of an inflammatory eye disease, preferably wherein the inflammatory eye disease isuveitis; and / or (b) the CD3 inhibitor or polynucleotide is administered in response to relapseof an inflammatory eye disease, preferably wherein the inflammatory eye disease is uveitis.

73. The product for use according to any of claims 66 or 68-72 or the method according to any of claims 67-72, wherein (a) the TNF inhibitor or polynucleotide is administered in the form ofa vector comprising a nucleotide sequence encoding a TNF inhibitor; and / or (b) the CD3inhibitor or polynucleotide is administered in the form of a vector comprising a nucleotide sequence encoding a CD3 inhibitor.

74. The product for use according to any of claims 66 or 68-73 or the method according to any of claims 67-73, wherein (a) the TNF inhibitor or polynucleotide is administered in the form of a pharmaceutical composition comprising the TNF inhibitor or polynucleotide; and / or (b) the CD3 inhibitor or polynucleotide is administered in the form of a pharmaceutical composition comprising the CD3 inhibitor or polynucleotide.

75. A vector comprising a nucleotide sequence encoding a CD3 inhibitor, wherein the nucleotide sequence encoding the CD3 inhibitor is operably linked to an inflammation- inducible promoter.

76. A vector comprising a nucleotide sequence having at least 70% identity to SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, or SEQ ID NO:

186.

77. An isolated cell comprising the vector according to claim 75 or 76.

78. A kit for the production of the vector of claim 75 or 76.

79. A pharmaceutical composition comprising the vector according to claim 75 or 76 or the isolated cell according to claim 77, in combination with a pharmaceutically acceptable carrier, diluent or excipient.

80. A vector according to claim 75 or 76, an isolated cell according to claim 77, and / or a pharmaceutical composition according to claim 79, for use as a medicament.

81. Use of a vector according to claim 75 or 76, an isolated cell according to claim 77, or a pharmaceutical composition according to claim 79, for the manufacture of a medicament.

82. A method comprising administering a vector according to claim 75 or 76, an isolated cell according to claim 77, or a pharmaceutical composition according to claim 79, to a subject in need thereof.

83. A vector for use in preventing or treating an inflammatory eye disease, wherein the vector comprises a nucleotide sequence encoding a CD3 inhibitor.

84. Use of a vector in the manufacture of a medicament for preventing or treating an inflammatory eye disease, wherein the vector comprises a nucleotide sequence encoding a CD3 inhibitor.

85. A method for preventing or treating an inflammatory eye disease, wherein the method comprises administering a vector to a subject in need thereof, wherein the vector comprises a nucleotide sequence encoding a CD3 inhibitor.

86. A vector according to claim 75 or 76, or a pharmaceutical composition according to claim 79, for use in preventing or treating an inflammatory eye disease.

87. Use of a vector according to claim 75 or 76, or a pharmaceutical composition according to claim 79, for the manufacture of a medicament for preventing or treating an inflammatory eye disease.

88. A method of preventing or treating an inflammatory eye disease comprising administering a vector according to claim 75 or 76, or a pharmaceutical composition according to claim 79, to a subject in need thereof.

89. A CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same, for use in preventing or treating an inflammatory eye disease, wherein the CD3 inhibitor or polynucleotide is administered intraocularly.

90. Use of a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encodingthe same, in the manufacture of a medicament for preventing or treating an inflammatory eyedisease, wherein the CD3 inhibitor or polynucleotide is administered intraocularly.

91. A method for preventing or treating an inflammatory eye disease, wherein the method comprises administering a CD3 inhibitor, or a polynucleotide comprising a nucleotide sequence encoding the same, to a subject in need thereof, wherein the CD3 inhibitor or polynucleotide is administered intraocularly.

Images