Chimeric antigen receptor

Abstract

The present invention provides a chimeric antigen receptor (CAR) comprising an antigen recognition domain that specifically binds to ASGPR, which may be expressed in immune cells, particularly Tregs. Such immune cells have therapeutic uses in diseases and conditions associated with cells that express ASGPR on their surface, such as uses in induction of tolerance to liver transplant, the treatment and / or prevention of liver transplant rejection, liver graft-versus-host disease (GvHD), an autoimmune liver disease, or an inflammatory liver disorder in a subject. Also provided are nucleic acid molecules encoding such CARs and vectors containing them that may be used to modify host cells to express the CARs. Also provided are cell populations comprising a plurality of such cells, pharmaceutical compositions comprising such cells, cell populations or vectors, and methods of making such cells.

Description

[0001]CHIMERIC ANTIGEN RECEPTOR TECHNICAL FIELD The present disclosure relates generally to the field of chimeric antigen receptors (CARs) and relatedtherapies, particularly adoptive cell transfer therapies. More particularly, the disclosure provides CARscomprising an antigen recognition domain that specifically binds to ASGPR, which may be expressed inimmune cells, particularly Tregs. Such immune cells have therapeutic uses in diseases and conditions associated with cells that express ASGPR on their surface. For example, such immune cells have therapeutic uses in induction of tolerance to liver transplant, the treatment and / or prevention of livertransplant rejection, liver graft-versus-host disease (GvHD), an autoimmune liver disease, or aninflammatory liver disorder in a subject. The disclosure further provides nucleic acid molecules encodingsuch CARs and vectors containing them that may be used to modify host cells, e.g., immune cells such asTregs, to express the CARs. The disclosure further provides cell populations comprising a plurality of cellsas described herein, pharmaceutical compositions comprising a cell, cell population or vector as describedherein, and methods of making the cells described herein.BACKGROUND Immunotherapy is emerging as a beneficial tool for the treatment of many conditions, ranging from cancer, autoimmune and inflammatory diseases, to the prevention of solid organ transplant rejection. In particular, there has been increased clinical activity in the area of adoptive cellular immunotherapy (ACT), particularly in regulatory T cell (Treg) cell therapies, across the autoimmune and inflammatory space. CD4+FOXP3+ regulatory T cells (Tregs) are a lymphocyte subset that is essential for the maintenance of dominant immunological tolerance by inhibiting the function of various effector immune cell subsets such as T effector cells. In addition, Tregs are also known to promote tissue repair and regeneration. Tregs areable to confer immune tolerance through multiple contact-dependent and independent mechanisms. Theseinclude production of anti-inflammatory soluble mediators such as IL-10, TGF-β and IL-35, consumption of IL-2, expression of negative regulatory cell surface receptors, such as CTLA-4, and targeting T cells directly or indirectly through APCs. Importantly, once activated, Tregs can suppress immune responses in a non- antigen specific fashion (bystander suppression), i.e., once activated, Tregs have the ability to modulate the local immune micro-environment and suppress inflammation. Furthermore, they can confer a suppressive phenotype on other cells of the immune system, a process called “infectious tolerance”. Artificial chimeric antigen receptors (CARs) have been used to confer antigen specificity on a cell. CARs are generally composed of an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signalling domain which sends signals into the cell and activates it upon binding of the antigen to the extracellular antigen-binding domain. However, CARs are artificial molecules engineered into cellsand are less sensitive than TCRs, partly due to the number of molecules involved in the TCR machinery,i.e., CD4 / CD8 co-receptors, immunoreceptor tyrosinase-rich activation motifs (ITAMs), and subunits withinthe receptor complex. It is therefore difficult to select a CAR which will specifically recognise its target andtrigger intracellular signalling to activate the cell in which it is expressed to desired levels. It may beparticularly desirable and advantageous to select CARs with low background activation / tonic signalling. Asialoglycoprotein receptor (ASGR or ASGPR) is a C-type lectin, primarily expressed on the sinusoidal surface of hepatocytes. ASGPR is formed of a major 48 kDa subunit (ASGPR1) and a minor 40 kDa subunit (ASGPR2). The major role of ASGPR is the binding, internalization and subsequence clearance from the circulation of glycoproteins that contain terminal galactose or N-acetylgalactosamine residues(asialoglycoproteins) (Roggenbuck, D. et al., 2012. Autoimmunity Highlights, 3(3), p 119). In normalhepatocytes, ASGPR is expressed in a polar manner on the sinusoidal and basolateral surface of the plasma hepatocyte membrane. However, during liver inflammation, ASGPR’s expression shifts towards thecanalicular membrane. In end-stage liver disease (cirrhosis), ASGPR is over-expressed and serum levelsof asialoglycoproteins are increased (Roggenbuck, D. et al., 2012. Autoimmunity Highlights, 3(3), p 119).Accordingly, there is a need for ASGPR-specific CARs that can be expressed in and subsequently activateimmune cells. SUMMARYThe present inventors have developed CARs which can specifically bind to ASGPR and activate the cellsin which they are expressed, particularly Tregs. In particular, the present inventors have developed CARswhich can specifically bind and subsequently activate cells in response to human antigen at physiological levels and in a physiological environment. Further, CARs have been identified which are able to sufficientlyactivate Tregs to promote their proliferation. In addition, the inventors have developed CARs which canactivate cells in response to both human and murine antigen, which may be particularly advantageous fortesting CARs intended for use in a human therapy in in vivo mouse models. An NSG mouse model hasbeen used to demonstrate that CAR-Tregs can specifically home to and become activated in the liver.The CARs of the present invention may particularly be expressed on the surface of immune cells in orderto target said immune cells to where ASGPR is expressed locally at the site of disease. In particular, theseCARs may be expressed on the surface of Tregs for the treatment of an autoimmune or inflammatorydisease where ASGPR is expressed locally at the site of disease (e.g. the liver), in view of the well-known bystander effect of Tregs and their ability, once activated, to reduce the immune response and modulate the activation status of other immune cell subsets.Accordingly, in one aspect there is provided a chimeric antigen receptor (CAR) which comprises an antigenrecognition domain which specifically binds to ASGPR. For example, the CAR may specifically bind to human ASGPR and / or murine ASGPR. For example, the CAR may specifically bind to human ASGPR1 and / or murine ASGPR1. In certain embodiments, the antigen recognition domain comprises a VH CDR3 having a sequence selected from SEQ ID NOs: 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, 117, 123, 129, 135, 141, 147, 153, 159, 165, 171, 177, 183, 189 and 195 or a sequence comprising from 1 to 3 amino acid modifications relative to one of SEQ ID NOs: 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87,93, 99, 105, 111, 117, 123, 129, 135, 141, 147, 153, 159, 165, 171, 177, 183, 189 and 195. Particularly,the aforementioned CDR sequence may optionally be modified by substitution, addition or deletion of 1, 2or 3 amino acids.In certain embodiments, the antigen recognition domain comprises a VL CDR3 having a sequence selectedfrom SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192 and 198 or a sequence comprising from 1 to 3 amino acid modifications relative to one of SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90,96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192 and 198. Particularly,the aforementioned CDR sequence may optionally be modified by substitution, addition or deletion of 1, 2 or 3 amino acids. In certain embodiments, the antigen recognition domain comprises VH CDR1, 2 and 3 sequences set forth in: (i) SEQ ID NOs: 1, 2 and 3 respectively;(ii) SEQ ID NOs: 7, 8 and 9 respectively;(iii) SEQ ID NOs: 13, 14 and 15 respectively;(iv) SEQ ID NOs: 19, 20 and 21 respectively;(v) SEQ ID NOs: 25, 26 and 27 respectively;(vi) SEQ ID NOs: 31, 32 and 33 respectively;(vii) SEQ ID NOs: 37, 38 and 39 respectively;(viii) SEQ ID NOs: 43, 44 and 45 respectively;(ix) SEQ ID NOs: 49, 50 and 51 respectively;(x) SEQ ID NOs: 55, 56 and 57 respectively;(xi) SEQ ID NOs: 61, 62 and 63 respectively;(xii) SEQ ID NOs: 67, 68 and 69 respectively;(xiii) SEQ ID NOs: 73, 74 and 75 respectively;(xiv) SEQ ID NOs: 79, 80 and 81 respectively;(xv) SEQ ID NOs: 85, 86 and 87 respectively;(xvi) SEQ ID NOs: 91, 92 and 93 respectively;(xvii) SEQ ID NOs: 97, 98 and 99 respectively;(xviii) SEQ ID NOs: 103, 104 and 105 respectively;(xix) SEQ ID NOs: 109, 110 and 111 respectively;(xx) SEQ ID NOs: 115, 116 and 117 respectively;(xxi) SEQ ID NOs: 121, 122 and 123 respectively;(xxii) SEQ ID NOs: 127, 128 and 129 respectively;(xxiii) SEQ ID NOs: 133, 134 and 135 respectively;(xxiv) SEQ ID NOs: 139, 140 and 141 respectively;(xxv) SEQ ID NOs: 145, 146 and 147 respectively;(xxvi) SEQ ID NOs: 151, 152 and 153 respectively;(xxvii) SEQ ID NOs: 157, 158 and 159 respectively;(xxviii) SEQ ID NOs: 163, 164 and 165 respectively;(xxix) SEQ ID NOs: 169, 170 and 171 respectively;(xxx) SEQ ID NOs: 175, 176 and 177 respectively;(xxxi) SEQ ID NOs: 181, 182 and 183 respectively;(xxxii) SEQ ID NOs: 187, 188 and 189 respectively; or(xxxiii) SEQ ID NOs: 193, 194 and 195 respectively;wherein one or more of said VH CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 aminoacid modifications relative to an aforementioned CDR sequence. Particularly, one, two or three of said CDRsequences of (i) to (xxxiii) may optionally be modified by substitution, addition or deletion of 1, 2 or 3 aminoacids. In certain embodiments, the antigen recognition domain comprises VL CDR1, 2 and 3 sequences set forth in: (i) SEQ ID NOs: 4, 5 and 6 respectively;(ii) SEQ ID NOs: 10, 11 and 12 respectively;(iii) SEQ ID NOs: 16, 17 and 18 respectively;(iv) SEQ ID NOs: 22, 23 and 24 respectively;(v) SEQ ID NOs: 28, 29 and 30 respectively;(vi) SEQ ID NOs: 34, 35 and 36 respectively;(vii) SEQ ID NOs: 40, 41 and 42 respectively;(viii) SEQ ID NOs: 46, 47 and 48 respectively;(ix) SEQ ID NOs: 52, 53 and 54 respectively;(x) SEQ ID NOs: 58, 59 and 60 respectively;(xi) SEQ ID NOs: 64, 65 and 66 respectively;(xii) SEQ ID NOs: 70, 71 and 72 respectively;(xiii) SEQ ID NOs: 76, 77 and 78 respectively;(xiv) SEQ ID NOs: 82, 83 and 84 respectively;(xv) SEQ ID NOs: 88, 89 and 90 respectively;(xvi) SEQ ID NOs: 94, 95 and 96 respectively;(xvii) SEQ ID NOs: 100, 101 and 102 respectively;(xviii) SEQ ID NOs: 106, 107 and 108 respectively;(xix) SEQ ID NOs: 112, 113 and 114 respectively;(xx) SEQ ID NOs: 118, 119 and 120 respectively;(xxi) SEQ ID NOs: 124, 125 and 126 respectively;(xxii) SEQ ID NOs: 130, 131 and 132 respectively;(xxiii) SEQ ID NOs: 136, 137 and 138 respectively;(xxiv) SEQ ID NOs: 142, 143 and 144 respectively;(xxv) SEQ ID NOs: 148, 149 and 150 respectively;(xxvi) SEQ ID NOs: 154, 155 and 156 respectively;(xxvii) SEQ ID NOs: 160, 161 and 162 respectively;(xxviii) SEQ ID NOs: 166, 167 and 168 respectively;(xxix) SEQ ID NOs: 172, 173 and 174 respectively;(xxx) SEQ ID NOs: 178, 179 and 180 respectively;(xxxi) SEQ ID NOs: 184, 185 and 186 respectively;(xxxii) SEQ ID NOs: 190, 191 and 192 respectively; or(xxxiii) SEQ ID NOs: 196, 197 and 198 respectively;wherein one or more of said VL CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3amino acid modifications relative to an aforementioned CDR sequence. Particularly, one, two or three ofsaid CDR sequences of (i) to (xxxiii) may optionally be modified by substitution, addition or deletion of 1, 2 or 3 amino acids. In certain embodiments, the antigen recognition domain of the CAR may be a single chain antibody (scFv).In certain embodiments, the antigen recognition domain comprises:(i) VH CDR 1, 2 and 3 sequences set forth in SEQ ID NOs: 1, 2 and 3 respectivelyand VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 4, 5 and 6 respectively;(ii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 7, 8 and 9 respectivelyand VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 10, 11 and 12respectively;(iii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 13, 14 and 15respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 16, 17 and 18 respectively;(iv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 19, 20 and 21respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 22, 23 and 24 respectively;(v) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 25, 26 and 27respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 28, 29 and 30 respectively;(vi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 31, 32 and 33respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 34, 35 and 36 respectively;(vii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 37, 38 and 39respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 40, 41 and 42 respectively;(viii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 43, 44 and 45respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 46, 47 and 48 respectively;(ix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 49, 50 and 51respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 52, 53 and 54 respectively;(x) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 55, 56 and 57respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 58, 59 and 60 respectively;(xi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 61, 62 and 63respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 64, 65 and 66 respectively;(xii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 67, 68 and 69respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 70, 71 and 72 respectively;(xiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 73, 74 and 75respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 76, 77and 78 respectively;(xiv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 79, 80 and 81respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 82, 83 and 84 respectively;(xv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 85, 86 and 87respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 88, 89 and 90 respectively;(xvi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 91, 92 and 93respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 94, 95 and 96 respectively;(xvii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 97, 98 and 99respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 100, 101 and 102 respectively;(xviii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 103, 104 and 105respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 106, 107 and 108 respectively;(xix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 109, 110 and 111respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 112, 113 and 114 respectively;(xx) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 115, 116 and 117respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 118, 119 and 120 respectively;(xxi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 121, 122 and 123respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 124, 125 and 126 respectively;(xxii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 127, 128 and 129respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 130, 131 and 132 respectively;(xxiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 133, 134 and 135respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 136, 137 and 138 respectively;(xxiv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 139, 140 and 141respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 142, 143 and 144 respectively;(xxv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 145, 146 and 147respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 148, 149 and 150 respectively;(xxvi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 151, 152 and 153respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 154, 155 and 156 respectively;(xxvii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 157, 158 and 159respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 160, 161 and 162 respectively;(xxviii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 163, 164 and 165respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 166, 167 and 168 respectively; (xxix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 169, 170 and 171respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 172, 173 and 174 respectively;(xxx) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 175, 176 and 177respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 178, 179 and 180 respectively;(xxxi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 181, 182 and 183respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 184,185 and 186 respectively;(xxxii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 187, 188 and 189respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 190, 191 and 192 respectively; or(xxxiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 193, 194 and 195respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 196, 197 and 198 respectively; wherein one or more of said CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 amino acid modifications relative to an aforementioned CDR sequence. Particularly, one, two, three, four, five or six ofsaid CDR sequences of (i) to (xxxiii) may optionally be modified by substitution, addition or deletion of 1, 2or 3 amino acids. In one embodiment, the antigen recognition domain of the CAR may comprise: (i) a VH domain comprising the sequence set forth in SEQ ID NO: 199, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 200, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto); (ii) a VH domain comprising the sequence set forth in SEQ ID NO: 201, or asequence having at least 70% identity thereto (optionally at least 80% or 90% identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 202, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(iii) a VH domain comprising the sequence set forth in SEQ ID NO: 203, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 204, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(iv) a VH domain comprising the sequence set forth in SEQ ID NO: 205, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 206, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(v) a VH domain comprising the sequence set forth in SEQ ID NO: 207, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 208, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(vi) a VH domain comprising the sequence set forth in SEQ ID NO: 209, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 210, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(vii) a VH domain comprising the sequence set forth in SEQ ID NO: 211, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 212, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(viii) a VH domain comprising the sequence set forth in SEQ ID NO: 213, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 214, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(ix) a VH domain comprising the sequence set forth in SEQ ID NO: 215, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQID NO: 216, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(x) a VH domain comprising the sequence set forth in SEQ ID NO: 217, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 218, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xi) a VH domain comprising the sequence set forth in SEQ ID NO: 219, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 220, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xii) a VH domain comprising the sequence set forth in SEQ ID NO: 221, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 222, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xiii) a VH domain comprising the sequence set forth in SEQ ID NO: 223, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 224, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xiv) a VH domain comprising the sequence set forth in SEQ ID NO: 225, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 226, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xv) a VH domain comprising the sequence set forth in SEQ ID NO: 227, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 228, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xvi) a VH domain comprising the sequence set forth in SEQ ID NO: 229, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 230, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xvii) a VH domain comprising the sequence set forth in SEQ ID NO: 231, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 232, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xviii) a VH domain comprising the sequence set forth in SEQ ID NO: 233, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 234, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xix) a VH domain comprising the sequence set forth in SEQ ID NO: 235, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 236, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xx) a VH domain comprising the sequence set forth in SEQ ID NO: 237, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 238, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxi) a VH domain comprising the sequence set forth in SEQ ID NO: 239, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 240, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxii) a VH domain comprising the sequence set forth in SEQ ID NO: 241, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 242, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxiii) a VH domain comprising the sequence set forth in SEQ ID NO: 243, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 244, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxiv) a VH domain comprising the sequence set forth in SEQ ID NO: 245, or asequence having at least 70% identity thereto (optionally at least 80% or 90% identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 246, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxv) a VH domain comprising the sequence set forth in SEQ ID NO: 247, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 248, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxvi) a VH domain comprising the sequence set forth in SEQ ID NO: 249, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 250, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxvii) a VH domain comprising the sequence set forth in SEQ ID NO: 251, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 252, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxviii) a VH domain comprising the sequence set forth in SEQ ID NO: 253, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 254, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxix) a VH domain comprising the sequence set forth in SEQ ID NO: 255, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 256, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxx) a VH domain comprising the sequence set forth in SEQ ID NO: 257, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 258, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto);(xxxi) a VH domain comprising the sequence set forth in SEQ ID NO: 259, or asequence having at least 70% identity thereto (optionally at least 80% or 90%identity thereto), and a VL domain comprising the sequence as set forth in SEQID NO: 260, or a sequence having at least 70% identity thereto (optionally atleast 80% or 90% identity thereto); (xxxii) a VH domain comprising the sequence set forth in SEQ ID NO: 261, or a sequencehaving at least 70% identity thereto (optionally at least 80% or 90% identitythereto), and a VL domain comprising the sequence as set forth in SEQ ID NO: 262, or a sequence having at least 70% identity thereto (optionally at least 80% or90% identity thereto); or (xxxiii) a VH domain comprising the sequence set forth in SEQ ID NO: 263, or a sequencehaving at least 70% identity thereto (optionally at least 80% or 90% identitythereto), and a VL domain comprising the sequence as set forth in SEQ ID NO:264, or a sequence having at least 70% identity thereto (optionally at least 80% or90% identity thereto).In one embodiment, the antigen recognition domain of the CAR may comprise or consist of:(i) the sequence set forth in SEQ ID NO: 265 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (ii) the sequence set forth in SEQ ID NO: 266 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (iii) the sequence set forth in SEQ ID NO: 267 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (iv) the sequence set forth in SEQ ID NO: 268 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (v) the sequence set forth in SEQ ID NO: 269 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (vi) the sequence set forth in SEQ ID NO: 270 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (vii) the sequence set forth in SEQ ID NO: 271 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (viii) the sequence set forth in SEQ ID NO: 272 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (ix) the sequence set forth in SEQ ID NO: 273 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (x) the sequence set forth in SEQ ID NO: 274 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (xi) the sequence set forth in SEQ ID NO: 275 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xii) the sequence set forth in SEQ ID NO: 276 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xiii) the sequence set forth in SEQ ID NO: 277 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xiv) the sequence set forth in SEQ ID NO: 278 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xv) the sequence set forth in SEQ ID NO: 279 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xvi) the sequence set forth in SEQ ID NO: 280 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xvii) the sequence set forth in SEQ ID NO: 281 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xviii) the sequence set forth in SEQ ID NO: 282 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xix) the sequence set forth in SEQ ID NO: 283 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xx) the sequence set forth in SEQ ID NO: 284 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxi) the sequence set forth in SEQ ID NO: 285 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxii) the sequence set forth in SEQ ID NO: 286 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxiii) the sequence set forth in SEQ ID NO: 287 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxiv) the sequence set forth in SEQ ID NO: 288 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxv) the sequence set forth in SEQ ID NO: 289 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxvi) the sequence set forth in SEQ ID NO: 290 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxvii) the sequence set forth in SEQ ID NO: 291 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxviii) the sequence set forth in SEQ ID NO: 292 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxix) the sequence set forth in SEQ ID NO: 293 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto;(xxx) the sequence set forth in SEQ ID NO: 294 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (xxxi) the sequence set forth in SEQ ID NO: 295 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; (xxxii) the sequence set forth in SEQ ID NO: 296 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto; or (xxxiii) the sequence set forth in SEQ ID NO: 297 or a sequence having at least 70%identity thereto, optionally at least 80% or 90% identity thereto. In certain embodiments, the CAR may comprise: a. an exodomain comprising the antigen recognition domain;b. a transmembrane domain; andc. an endodomain comprising an intracellular signalling domain.The CAR may further comprise a hinge domain and / or one or more co-stimulatory domains. The term “hinge domain” typically refers to the portion of the exodomain that connects the antigen recognition domain with the transmembrane domain. The hinge domain may be selected from the hinge regions of CD28, CD8α, CD4, CD7, CH2CH3, an immunoglobulin, or a part or variant thereof. Preferably, the CAR may comprise a CD8α or CH2CH3 hinge domain. The co-stimulatory domain may be selected from the intracellular domains of CD28, ICOS, CD134 (OX40), CD137 (4-1BB), CD27, or TNFRSF25, or a part or variant thereof. Preferably, the CAR may comprise a CD28 co-stimulatory domain.The CAR may comprise one or more transmembrane domains, which may be selected from thetransmembrane domains of CD28, ICOS, CD8α, CD4, CD134 (OX40), CD137 (4-1BB), CD3 zeta, CD45, CD9, CD16, CD22, CD33, CD64, CD80, CD86, CD154, or a part or variant thereof. Preferably, the CAR comprises a CD28 or CD8α transmembrane domain. The CAR (specifically the endodomain of the CAR) may comprise one or more intracellular signalling domains selected from the group consisting of the CD3 zeta signalling domain or any of its homologs, a CD3 polypeptide, a syk family tyrosine kinase, a src family tyrosine kinase, CD2, CD5, and CD28, or a part or variant thereof. Preferably, the CAR may comprise the CD3 zeta signalling domain. In one embodiment, the CAR may comprise a CD8α or CH2CH3 hinge domain (i.e. a hinge domain derived from CD8α or CH2CH3); a CD8α or CD28 transmembrane domain (i.e. a transmembrane domain derived from CD8α or CD28); a CD28 co-stimulatory domain (i.e. a co-stimulatory domain derived from CD28); and the CD3 zeta signalling domain (i.e. a signalling domain derived from CD3 zeta), wherein when the hinge domain is a CD8α hinge domain, the transmembrane domain is a CD8α transmembrane domain, and when the hinge domain is a CH2CH3 hinge domain, the transmembrane domain is a CD28 transmembrane domain. Alternatively viewed, in one embodiment, the CAR may comprise a CD8α hinge domain, a CD8α transmembrane domain, a CD28 co-stimulatory domain, and the CD3 zeta signalling domain. In a separate embodiment, the CAR may comprise a CH2CH3 hinge domain, a CD28 transmembrane domain, a CD28 co-stimulatory domain, and the CD3 zeta signalling domain. The CAR of the present invention may comprise a signal peptide and / or a reporter peptide. In one embodiment, the polynucleotide sequence encoding a CAR of the present invention may comprise a further polynucleotide sequence encoding a reporter peptide linked by a self-cleaving or cleavage domain.The CAR of the present invention may comprise or consist of:(i) the sequence set forth in SEQ ID NO: 298 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(ii) the sequence set forth in SEQ ID NO: 299 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (iii) the sequence set forth in SEQ ID NO: 300 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (iv) the sequence set forth in SEQ ID NO: 301 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (v) the sequence set forth in SEQ ID NO: 302 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (vi) the sequence set forth in SEQ ID NO: 303 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (vii) the sequence set forth in SEQ ID NO: 304 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (viii) the sequence set forth in SEQ ID NO: 305 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (ix) the sequence set forth in SEQ ID NO: 306 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (x) the sequence set forth in SEQ ID NO: 307 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (xi) the sequence set forth in SEQ ID NO: 308 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); (xii) the sequence set forth in SEQ ID NO: 309 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xiii) the sequence set forth in SEQ ID NO: 310 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xiv) the sequence set forth in SEQ ID NO: 311 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xv) the sequence set forth in SEQ ID NO: 312 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xvi) the sequence set forth in SEQ ID NO: 313 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xvii) the sequence set forth in SEQ ID NO: 314 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xviii) the sequence set forth in SEQ ID NO: 315 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xix) the sequence set forth in SEQ ID NO: 316 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xx) the sequence set forth in SEQ ID NO: 317 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxi) the sequence set forth in SEQ ID NO: 318 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxii) the sequence set forth in SEQ ID NO: 319 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxiii) the sequence set forth in SEQ ID NO: 320 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxiv) the sequence set forth in SEQ ID NO: 321 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxv) the sequence set forth in SEQ ID NO: 322 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxvi) the sequence set forth in SEQ ID NO: 323 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxvii) the sequence set forth in SEQ ID NO: 324 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxviii) the sequence set forth in SEQ ID NO: 325 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxix) the sequence set forth in SEQ ID NO: 326 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxx) the sequence set forth in SEQ ID NO: 327 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxi) the sequence set forth in SEQ ID NO: 328 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxii) the sequence set forth in SEQ ID NO: 329 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxiii) the sequence set forth in SEQ ID NO: 330 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxiv) the sequence set forth in SEQ ID NO: 331 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxv) the sequence set forth in SEQ ID NO: 332 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxvi) the sequence set forth in SEQ ID NO: 333 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxvii) the sequence set forth in SEQ ID NO: 334 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxviii) the sequence set forth in SEQ ID NO: 335 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xxxix) the sequence set forth in SEQ ID NO: 336 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xl) the sequence set forth in SEQ ID NO: 337 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xli) the sequence set forth in SEQ ID NO: 338 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xlii) the sequence set forth in SEQ ID NO: 339 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xliii) the sequence set forth in SEQ ID NO: 340 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xliv) the sequence set forth in SEQ ID NO: 341 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xlv) the sequence set forth in SEQ ID NO: 342 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xlvi) the sequence set forth in SEQ ID NO: 343 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xlvii) the sequence set forth in SEQ ID NO: 344 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xlviii) the sequence set forth in SEQ ID NO: 345 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(xlix) the sequence set forth in SEQ ID NO: 346 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(l) the sequence set forth in SEQ ID NO: 347 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(li) the sequence set forth in SEQ ID NO: 348 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lii) the sequence set forth in SEQ ID NO: 349 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(liii) the sequence set forth in SEQ ID NO: 350 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(liv) the sequence set forth in SEQ ID NO: 351 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lv) the sequence set forth in SEQ ID NO: 352 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lvi) the sequence set forth in SEQ ID NO: 353 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lvii) the sequence set forth in SEQ ID NO: 354 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lviii) the sequence set forth in SEQ ID NO: 355 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lix) the sequence set forth in SEQ ID NO: 356 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lx) the sequence set forth in SEQ ID NO: 357 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lxi) the sequence set forth in SEQ ID NO: 358 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lxii) the sequence set forth in SEQ ID NO: 359 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lxiii) the sequence set forth in SEQ ID NO: 360 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lxiv) the sequence set forth in SEQ ID NO: 361 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto);(lxv) the sequence set forth in SEQ ID NO: 362 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto); or(lxvi) the sequence set forth in SEQ ID NO: 363 or a sequence having at least 70%identity thereto (optionally at least 80% or 90% identity thereto). The CAR of the present invention may comprise or consist of a sequence encoded by the sequence set forth in any of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence having at least 70% identity (optionally at least 80% or 90% identity) to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443 respectively. In a second aspect, the invention provides a nucleic acid molecule comprising a nucleotide sequence encoding the CAR according to the invention. The nucleic acid molecule may comprise the sequence set forth in any of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence encoding a CAR having at least 70% identity (optionally at least 80% or 90% identity) to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443 respectively. In a third aspect, the invention provides a vector comprising the nucleic acid molecule according to the invention. The vector may further comprise a nucleic acid molecule comprising a nucleotide sequenceencoding a FOXP3 polypeptide, or a derivative or variant thereof.In a further aspect, the invention provides a cell comprising the CAR, nucleic acid molecule or vector according to the invention. The cell may further comprise an exogenous FOXP3 polypeptide or an exogenous nucleic acid encoding FOXP3. The cell may be an immune cell or a progenitor or precursor thereof. Preferably, the cell may be a T cell, or a precursor thereof, or a stem cell. In particular, the cell may be a Treg, or a precursor thereof, or an iPSC cell. The cell may be a production host cell. In a specificembodiment, the invention provides a Treg comprising a CAR, nucleic acid or vector according to theinvention. The cell may be provided in a cell population, which forms a further aspect of the invention. In particular, the cell population may comprise a plurality of cells according to the invention, particularly a plurality of T cells (e.g. a plurality of Tregs) according to the invention. The invention also provides a pharmaceutical composition comprising the cell, cell population or vector according to the invention. In another aspect, the invention provides a cell, cell population or pharmaceutical composition according tothe invention for use in therapy or for use in the manufacture of a medicament for use in therapy (e.g., foruse in treating and / or preventing an autoimmune or inflammatory disease, or for use in inducing immunosuppression, or for use in promoting tissue repair and / or tissue regeneration). The therapy may be adoptive cell transfer therapy. Alternatively viewed, the invention provides a method for treating and / or preventing an autoimmune or inflammatory disease, or for inducing immunosuppression, or for promoting tissue repair and / or tissue regeneration, wherein the method comprises administering a cell, particularly a Treg cell, a cell population, or a pharmaceutical composition, particularly comprising a Treg, according to the invention. In this respect, the method may comprise the following steps: (i) isolation or provision of a Treg-enriched cell sample from a subject;(ii) introduction into the Treg cells of a nucleic acid molecule or vector of the invention; and(iii) administering the Treg cells from (ii) to the subject.The invention also provides use of a cell, cell population or pharmaceutical composition according to the invention in the manufacture of a medicament for treating and / or preventing an autoimmune or inflammatory disease, or for inducing immunosuppression, or for promoting tissue repair and / or tissue regeneration in a subject, particularly wherein the cell is a Treg cell. In particular, the cell, cell population or pharmaceutical composition according to the invention may be used for the induction of tolerance to a liver transplant in a subject, or for the treatment and / or prevention of liver transplant rejection, liver graft-versus-host disease (GvHD), an autoimmune liver disease, or aninflammatory liver disorder in a subject. The autoimmune liver disease may be biliary cholangitis and / orprimary sclerosing cholangitis. The inflammatory liver disorder may be liver cirrhosis, acute liver failure oracute-on-chronic liver failure. The liver inflammation may be caused by alcohol, viral hepatitis, steatohepatitis, ischemia or drug toxicity or may have no identifiable cause. In particular, the cell, cell population or pharmaceutical composition according to the invention may be used to promote liver repair or to regenerate liver tissue in a subject. The liver may have been injured and / or damaged by ischemia, partial hepatectomy, or inflammation. The inflammation may be liver cirrhosis, acute liver failure or acute-on-chronic liver failure. The inflammation may be caused by alcohol, viral hepatitis, steatohepatitis, ischemia or drug toxicity, or may have no identifiable cause. The subject may have impaired liver regeneration, for example due to one or more of acute liver failure, cirrhosis, acute-on-chronic liver failure, hepatitis, steatosis, steatohepatitis and old age. The subject of the uses and methods described herein may be a mammal, particularly a human. In another aspect, the invention provides a method of making a cell according to the invention, which comprises the step of introducing into the cell (e.g., transducing or transfecting a cell with) the nucleic acidmolecule or vector according to the invention. The cell may be a Treg cell, and the method may compriseisolating or providing a cell-containing sample comprising Tregs, and / or enriching Tregs or generating Tregsfrom the cell-containing sample prior to or after the step of introducing the nucleic acid molecule or vectorinto the cell. The invention also provides a cell obtainable by this method, which forms a further aspect of the invention. BRIEF DESCRIPTION OF THE FIGURESFigures 1 and 2 show the results of the Jurkat NFAT activation assays described in Example 1 below.Figure 3 shows the transduction efficiency of Tregs prepared according to Example 2 below.Figure 4 shows FOXP3 and Helios expression in the transduced fraction and untransduced fraction of Tregsprepared according to Example 2 below.Figure 5 shows the results of the Treg activation assay described in Example 2 below.Figure 6 shows the results of the Treg proliferation assay described in Example 2 below.Figure 7 shows the number of CAR+ cells present in the spleen, lung and liver of NSG mice administeredcells as described in Example 3 below. Figure 8 shows the % of activated cells (indicated by CD69 expression) in the blood, spleen, lung and liverof NSG mice administered cells as described in Example 3 below.Figure 9 shows the % of GFP+ cells present pre-injection and at days 5 and 10 post-injection in the liver, blood and spleen of NSG mice administered cells as described in Example 3 below. Figure 10 shows the % of activated cells (indicated by CD69 expression) in PCLS supernatant or PCLStissue following incubation with CAR-Teff cells as described in Example 4 below (n = 1).Figure 11 shows % of activated cells (indicated by CD69 expression) in PCLS supernatant or PCLS tissue following incubation with CAR-Teff cells as described in Example 4 below (n = 3).Figure 12A shows % of CD4+CAR+ Teffs expressing the activation marker CD69 when injected alone, withmock Tregs or with CAR-Tregs and figure 12B shows % of CD4+CAR- Teffs expressing the activationmarker CD69 when injected alone or with CAR-Tregs. Figure 13 shows % of transduced and untransduced Tregs expressing the activation marker CD69 following injection to mice together with CAR Teffs. Figure 14 shows serum AST levels in mice following injection with CAR-Teffs only, CAR-Teffs with mock Tregs and CAR-Teffs with CAR-Tregs. Figure 15 shows serum IFNγ levels in mice following injection with CAR-Teffs only or CAR-Teffs with CAR- Tregs.Figure 16A shows % Teff suppression by CAR-Tregs following activation by CD3 / CD28 beads and / or Bcells expressing ASGPR1. As a negative control, cells were exposed to WT B cells. Figure 16B shows the difference in area under the under (ΔAUC) for Teff suppression shown in Figure 16B (ΔAUC = % suppression when exposed to ASGPR1+ B cells minus % suppression when exposed to WT B cells). Figure 17 shows % expression of Treg phenotype markers in mock Tregs (right-hand bars for each marker) and CAR-Tregs (left-hand bars for each marker). DETAILED DESCRIPTIONThe present invention provides CARs that specifically bind to ASGPR and provide an activation signal tocells in which they are expressed, particularly immune cells in which they are expressed. Thus, these CAR-expressing immune cells have therapeutic potential in treating diseases or disorders where ASGPR isexpressed locally at the site of disease (e.g. the liver). In particular, Tregs expressing these CARs havetherapeutic potential for the induction of tolerance to a liver transplant or treating or preventing livertransplant rejection, liver graft-versus-host disease (GvHD), an autoimmune liver disease, or an inflammatory liver disorder in a subject. Further, Tregs expressing these CARs have therapeutic potential in repairing and / or regenerating liver tissue in a subject. Accordingly, the present invention provides a CAR comprising an antigen recognition domain that specifically binds to ASGPR. A “chimeric antigen receptor", "CAR" or “CAR construct” refers to engineered receptors which can confer an antigen specificity onto cells (e.g., immune cells, such as Tregs). In particular, a CAR enables a cell to bind specifically to a particular antigen, e.g., a target molecule such as a target protein, whereupon a signal is generated by the endodomain (comprising an intracellular signalling domain) of the CAR, e.g., a signal resulting in activation of the cell. CARs are also known as artificial T-cell receptors, chimeric T-cell receptors or chimeric immunoreceptors. The structure of CARs is well-known in the art and several generations of CARs have been produced. For instance, as a minimum a CAR may contain an extracellular antigen-specific targeting region, antigen binding domain, target binding domain or ligand binding domain, which is or forms part of the exodomain (also known as the extracellular domain or ectodomain) of the CAR, a transmembrane domain, and an intracellular signalling domain (which is, or is comprised within, an endodomain). However, the CAR may contain further domains to improve its functionality, e.g., one or more co-stimulatory domains to improve Tcell proliferation, cytokine secretion, resistance to apoptosis, and in vivo persistence.Thus, a chimeric receptor or CAR construct generally comprises a binding domain (which may be viewed as an antigen (i.e., target) or ligand binding domain and the terms binding domain, antigen recognition domain, antigen binding domain and ligand binding domain are used interchangeably herein), optionally a hinge domain, which functions as a spacer to extend the binding domain away from the plasma membrane of the cell (e.g., immune cell) on which it is expressed, a transmembrane domain, an intracellular signalling domain (e.g., the signalling domain from the zeta chain of the CD3 molecule (CD3ζ) of the TCR complex, or an equivalent) and optionally one or more co-stimulatory domains, which may assist in signalling or functionality of the cell expressing the CAR. A CAR may also comprise a signal or leader sequence or domain which functions to target the protein to the membrane and may form part of the exodomain of the CAR. The different domains may be linked directly or by linkers, and / or may occur within different polypeptides, e.g., within two polypeptides which associate with one another. When the CAR binds its target antigen (i.e., ASGPR), this results in the transmission of an activating signalto the cell in which it is expressed. Thus, the CAR directs the specificity of the engineered cells towardsASGPR, particularly towards cells expressing ASGPR. The term “directed towards” or “directed against” is synonymous with “specific for” or “anti”. Put anotherway, the CAR recognises the ASGPR target molecule. Accordingly, it is meant that the CAR is capable ofbinding specifically to ASGPR. In particular, the antigen-binding domain of the CAR is capable of bindingspecifically to ASGPR (more particularly when the CAR is expressed on the surface of a cell, notably animmune effector cell). Specific binding may be distinguished from non-specific binding to a non-target molecule or antigen. Thus, a cell expressing the CAR is directed, or re-directed, to bind specifically to atarget cell, expressing ASGPR, particularly a target cell expressing ASGPR on its cell surface. Particularly,“specific” binding means that binding only or mainly occurs to ASGPR and not to other proteins orpolypeptides (i.e., binding to other proteins or polypeptides is insignificant or weaker). Some cross-reaction with other proteins may occur but this level of binding can be considered as background. As mentionedabove, the CAR is capable of binding to ASGPR and of transducing a signal into a cell in which it isexpressed. The cell may then be activated and may exert a suppressive effect within the localenvironment. Activation of a cell expressing a CAR after antigen binding can be determined by anincreased level of CD69 as compared to the same cells expressing a CAR in the absence of antigen. Forexample, an increase of at least 10, 20, 30, 40, 50, 60, 70, 80 or 90% in CD69. Expression levels of CD69can be determined using standard techniques, for example FACS, using commercially available antibodies(e.g. FITC anti-human CD69 antibody, Biolegend). Thus, CAR function within a cell can be determined byactivation status of the cell in which the CAR is expressed, e.g., by determining CD69 expression. Asialoglycoprotein receptor (ASGR or ASGPR) is a C-type lectin, primarily expressed on the sinusoidal surface of hepatocytes. ASGPR is formed of a major 48 kDa subunit (ASGPR1) and a minor 40 kDa subunit (ASGPR2). The major role of ASGPR is the binding, internalization and subsequence clearance from the circulation of glycoproteins that contain terminal galactose or N-acetylgalactosamine residues(asialoglycoproteins) (Roggenbuck, D. et al., 2012. Autoimmunity Highlights, 3(3), p 119). In normalhepatocytes, ASGPR is expressed in a polar manner on the sinusoidal and basolateral surface of the plasma hepatocyte membrane. However, during liver inflammation, ASGPR’s expression shifts towards the canalicular membrane. In end-stage liver disease (cirrhosis), ASGPR is over-expressed and serum levels of asialoglycoproteins are increased (Roggenbuck, D. et al., 2012. Autoimmunity Highlights, 3(3), p 119). Human ASGPR1 (UniProt entry P07306) is encoded by the ASGR1 gene. Spliced transcript variants encoding multiple isoforms have been observed for this gene (Harris, R.L., et al. , 2012. Molecular biology international, 2012, Article ID 283974, 10 pages). The longer transcript contains all 8 exons, is by far the more abundant, and encodes full-length ASGPR1 (isoform a, 291 amino acids). The shorter transcript has an in-frame deletion of exon 3 resulting in the loss of 39 residues (isoform b, 252 amino acids). Isoform b lacks the transmembrane domain and is secreted as a soluble protein. Illustrative sequences of humanASGPR1 isoforms a and b are shown as SEQ ID NOs: 364 and 365 respectively.Human ASGPR2 (UniProt entry P07307) is encoded by the ASGR2 gene. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene (Harris, R.L., et al., 2012. Molecular biology international, 2012, Article ID 283974, 10 pages). ASGR2 gives rise to five transcripts (TH2', T1, T2, T3, and T4) encoding four isoforms (a to d) that contain different in-frame deletions arising from alternative exon splicing events. Isoforms a and c contain 5 amino acids that serve as a proteolysis cleavage signal near the junction between the transmembrane domain and the CRD. Isoforms b and d lack this signal therefore they are not proteolytically cleaved but rather remain membrane bound where they may oligomerize with ASGPR1 isoform a, to form native ASGPR at the cell surface. Illustrative sequences ofASGPR2 isoforms a-d are shown below (SEQ ID NOs: 366 to 369).The antigen recognition domain may bind, suitably specifically bind, one or more region or epitope within ASGPR. An epitope, also known as antigenic determinant, is the part of an antigen that is recognised by an antigen recognition domain (e.g. an antibody). In other words, the epitope is the specific piece of the antigen to which an antigen recognition domain binds. Suitably, the antigen recognition domain binds, suitably specifically binds, to one region or epitope within ASGPR. The antigen recognition domain used in the present invention may selectively or specifically bind to ASGPR,and thus may have a greater binding affinity for ASGPR as compared to its binding affinity for otherproteins / molecules. Suitably, “specifically binds” as used herein means that the antigen recognition domain does not bind to other proteins or binds with a greatly reduced affinity compared to the binding to the antigen to which it specifically binds (e.g. with an affinity of at least 10, 50, 100, 500, 1000 or 10000 times less than its affinity for the antigen to which it specifically binds). Thus, the antigen recognition domain as referred to herein may bind to ASGPR with at least 10, 50, 100, 500, 1000 or 10000 times the affinity of its binding to other proteins. The binding affinity of the antigen recognition domain can be determined using methods well known in the art such as with the Biacore system. The antigen-binding domain of a CAR may be derived or obtained from any protein or polypeptide whichbinds (i.e., has affinity for) ASGPR (e.g. which binds to any region or part of ASGPR, or alternatively viewedwhich binds to any epitope within ASGPR, either in an isolated protein form or when expressed on cells). Particularly, the antigen-binding domain of a CAR may be derived or obtained from any protein or polypeptide which binds (i.e., has affinity for) the extracellular domain of ASGPR. This may be for example, a physiological binding protein for ASGPR, or a part thereof, or a synthetic or derivative protein. The target molecule (i.e., ASGPR) may commonly be expressed on the surface of a cell, for example a target cell(e.g., a liver cell), or a cell in the vicinity of a target cell (for a bystander effect), but need not be.The antigen-binding domain is most commonly derived from antibody variable chains (for example it commonly takes the form of a scFv), but may also be generated from other molecules, such as ligands or other binding molecules. The CAR is typically expressed as a polypeptide also comprising a signal sequence (also known as a leader sequence), and in particular a signal sequence which targets the CAR to the plasma membrane of the cell. This will generally be positioned next to or close to the antigen binding domain, generally upstream of the antigen binding domain. The extracellular domain, or ectodomain, of the CAR may thus comprise, consistessentially of or consist of a signal sequence and an antigen binding domain. The extracellular domain, orectodomain, of the CAR may comprise, consist essentially of or consist of a signal sequence, an antigenbinding domain, and a hinge domain. As noted above, the antigen binding domain may be any protein or peptide that possesses the ability to specifically recognize and bind to ASGPR. The antigen binding domain includes any naturally occurring,synthetic, semi-synthetic, or recombinantly produced binding partner for ASGPR. Illustrative antigen-specific targeting domains include antibodies or antibody fragments or derivatives, or ligands for ASGPR. In an embodiment, the antigen binding domain is, or is derived from, an antibody. The term “antibody” as used herein refers broadly to any immunological binding agent or molecule that comprises an antigen binding domain, including polyclonal and monoclonal antibodies. Depending on the type of constant domain in the heavy chains, whole antibodies are assigned to one of five major classes: IgA, IgD, IgE, IgG and IgM and the antibodies as described herein may be in any one of these classes. Several of these are further divided into subclasses or isotypes such as IgG1, IgG2, IgG3, IgG4 and the like. Generally, IgG or IgM antibodies are the most common antibodies utilised in physiological settings. As will be understood bythose in the art, the term “antibody” extends to all antibodies including whole antibodies, dimeric, trimericand multimeric antibodies; bispecific antibodies; chimeric antibodies; recombinant and engineered antibodies and fragments thereof. An antibody-derived binding domain can be a fragment of an antibody or a genetically engineered product of one or more fragments of the antibody, which fragment is involved in binding with the antigen. Examplesinclude a variable region (Fv), a complementarity determining region (CDR), Fab or F(ab’)2, or the light andheavy chain variable regions can be joined together in a single chain (e.g. as a scFv) and in eitherorientation (e.g. VL-VH or VH-VL). The VL and / or VH sequences may be modified. In particular, the frameworkregions may be modified (e.g., substituted, for example to humanise the antigen-binding domain). Otherexamples include a heavy chain variable region (VH), a light chain variable region (VL) and a single domain antibody (sdAb) which may be referred to as a nanobody. An example of a single domain antibody is a camelid heavy-chain antibody (HCAb) which has an antigen recognition site formed by a single domain, termed VHH.In a preferred embodiment, the antigen-binding domain is a single chain antibody (scFv). The scFv maybe murine, human or humanized scFv. “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 (although some framework regions are known to be involved in binding). The heavy chain variable region and the light chain variable region of an antibody each contain 3 CDRs. "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 are more highly conserved than the CDRs and form a scaffold to support the CDRs. "Light chain variable region" or "VL" refers to the fragment of the light chain of an antibody that contains three CDRs interposed between framework regions. "Fv" refers to the smallest fragment of an antibody to bear the complete antigen binding site. An Fv fragment consists of the variable region of a single light chain bound to the variable region of a single heavychain. "Single-chain Fv antibody" or "scFv" refers to an engineered antibody consisting of a light chainvariable region and a heavy chain variable region connected to one another, in either orientation, directly or via a peptide linker sequence. Antibodies that specifically bind a predetermined antigen, i.e., ASGPR, can be prepared using methodswell known in the art. Such methods include phage display, methods to generate human or humanizedantibodies, or methods using a 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, i.e., to ASGPR. Phage display libraries of human antibodies are also available. Once identified, the amino acid sequence or polynucleotide sequence coding for the antibody can be isolated and / or determined. The antigen recognition domain may bind, suitably specifically bind, one or more regions or epitopes within ASGPR. An epitope, also known as antigenic determinant, is the part of an antigen that is recognised by an antigen recognition domain (e.g., an antibody). In other words, the epitope is the specific piece of the antigen to which an antibody binds. Suitably, the antigen recognition domain binds, suitably specifically binds, to one region or epitope within ASGPR.The antigen recognition domain of the CAR may comprise at least one CDR (e.g. CDR3), which can bepredicted from an antibody which binds to an antigen, i.e., ASGPR (or a variant of such a predicted CDR(e.g. a variant with one, two or three amino acid substitutions)). It will be appreciated that molecules containing three or fewer CDR regions (e.g. a single CDR or even a part thereof) may be capable ofretaining the antigen-binding activity of the antibody from which the CDR is derived. Molecules containingtwo CDR regions are described in the art as being capable of binding to a target antigen, e.g. in the form of a minibody (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 (Nicaise et al, 2004, Protein Science, 13: 1882-91). In this respect, the antigen binding domain may comprise one or more variable heavy chain CDRs, e.g., one, two or three variable heavy chain CDRs. Alternatively, or additionally, the antigen binding domain may comprise one or more variable light chain CDRs, e.g. one, two or three variable light chain CDRs. The antigen binding domain may comprise three heavy chain CDRs and / or three light chain CDRs (and more particularly a heavy chain variable region comprising three CDRs and / or a light chain variable region comprising three CDRs) wherein at least one CDR, preferably all CDRs, may be from an antibody which binds to ASGPR. The antigen binding domain 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 or three 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 variable light chain CDRs. Preferably, the antigen binding domain comprises three variable heavy chain CDRs (CDR1, CDR2 and CDR3) and / or three variable light chain CDRs (CDR1, CDR2 and CDR3). The one or more CDRs present within the antigen binding domain may not all be from the same antibody, as long as the domain has the desired binding activity. Thus, one CDR may be predicted from the heavy orlight chains of an antibody which binds to ASGPR whilst another CDR present may be predicted from adifferent antibody which binds to ASGPR. A combination of CDRs may be used from different antibodies, particularly from antibodies that bind to the same desired region or epitope. In a particularly preferred embodiment, the antigen binding domain comprises three CDRs predicted fromthe variable heavy chain sequence of an antibody which binds to ASGPR and / or three CDRs predictedfrom the variable light chain sequence of an antibody which binds to ASGPR (preferably the same antibody).In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 3 and / or a VL CDR3 sequence set forth in SEQ ID NO: 6, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR.In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 1, 2 and 3 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions)compared to one of SEQ ID NOs: 1, 2 and 3. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 4, 5 and 6 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 4, 5 and 6. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 1, 2 and 3 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 4, 5 and 6 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 1 to 6. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 199 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 200 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 265 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto).In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 9 and / or a VL CDR3 sequence set forth in SEQ ID NO: 12, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 7, 8 and 9 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 7, 8 and 9. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 10, 11 and 12 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 10, 11 and 12. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 7, 8 and 9 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 10, 11 and 12 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 7 to 12.In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 201 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 202 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 266 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 15 and / or a VL CDR3 sequence set forth in SEQ ID NO: 18, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 13, 14 and 15 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 13, 14 and 15. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 16, 17 and 18 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 16, 17 and 18. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 13, 14 and 15 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 16, 17 and 18 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one ofSEQ ID NOs: 13 to 18.In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 203 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 204 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 267 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 21 and / or a VL CDR3 sequence set forth in SEQ ID NO: 24, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 19, 20 and 21 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions)compared to one of SEQ ID NOs: 19, 20 and 21. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 22, 23 and 24 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 22, 23 and 24. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 19, 20 and 21 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 22, 23 and 24 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 19 to 24. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 205 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 206 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 268 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 27 and / or a VL CDR3 sequence set forth in SEQ ID NO: 30, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 25, 26 and 27 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 25, 26 and 27. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 28, 29 and 30 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 28, 29 and 30. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 25, 26 and 27 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 28, 29 and 30 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 25 to 30. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 207 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 208 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 269 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 33 and / or a VL CDR3 sequence set forth in SEQ ID NO: 36, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 31, 32 and 33 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 31, 32 and 33. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 34, 35 and 36 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 34, 35 and 36. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 31, 32 and 33 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 34, 35 and 36 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 31 to 36. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 209 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 210 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 270 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 39 and / or a VL CDR3 sequence set forth in SEQ ID NO: 42, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications(e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 37, 38 and 39 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 37, 38 and 39. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 40, 41 and 42 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 40, 41 and 42. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 37, 38 and 39 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 40, 41 and 42 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 37 to 42. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 211 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 212 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 271 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 45 and / or a VL CDR3 sequence set forth in SEQ ID NO: 48, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 43, 44 and 45 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions)compared to one of SEQ ID NOs: 43, 44 and 45. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 46, 47 and 48 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 46, 47 and 48. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 43, 44 and 45 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 46, 47 and 48 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 43 to 48. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 213 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 214 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 272 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 51 and / or a VL CDR3 sequence set forth in SEQ ID NO: 54, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 49, 50 and 51 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions)compared to one of SEQ ID NOs: 49, 50 and 51. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 52, 53 and 54 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 52, 53 and 54. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 49, 50 and 51 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 52, 53 and 54 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 49 to 54. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 215 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 216 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto).In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 273 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 57 and / or a VL CDR3 sequence set forth in SEQ ID NO: 60, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 55, 56 and 57 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 55, 56 and 57. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 58, 59 and 60 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 58, 59 and 60. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 55, 56 and 57 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 58, 59 and 60 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one ofSEQ ID NOs: 55 to 60. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 217 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 218 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 274 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 63 and / or a VL CDR3 sequence set forth in SEQ ID NO: 66, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 61, 62 and 63 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 61, 62 and 63.In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 64, 65 and 66 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 64, 65 and 66. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 61, 62 and 63 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 64, 65 and 66 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 61 to 66. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 219 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 220 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 275 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 69 and / or a VL CDR3 sequence set forth in SEQ ID NO: 72, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 67, 68 and 69 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 67, 68 and 69. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 70, 71 and 72 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 70, 71 and 72.In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 67, 68 and 69 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 70, 71 and 72 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 67 to 72. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 221 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 222 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 276 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 75 and / or a VL CDR3 sequence set forth in SEQ ID NO: 78, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 73, 74 and 75 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 73, 74 and 75. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 76, 77 and 78 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 76, 77 and 78. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 73, 74 and 75 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 76, 77 and 78 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 73 to 78. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 223 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 224 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 277 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 81 and / or a VL CDR3 sequence set forth in SEQ ID NO: 84, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 79, 80 and 81 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 79, 80 and 81. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 82, 83 and 84 respectively, wherein one or more of said VL CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 82, 83 and 84. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 79, 80 and 81 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 82, 83 and 84 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 79 to 84. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 225 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 226 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 278 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 87 and / or a VL CDR3 sequence set forth in SEQ ID NO: 90, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications(e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 85, 86 and 87 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 85, 86 and 87. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 88, 89 and 90 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 88, 89 and 90. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 85, 86 and 87 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 88, 89 and 90 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 85 to 90. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 227 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 228 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 279 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 93 and / or a VL CDR3 sequence set forth in SEQ ID NO: 96, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 91, 92 and 93 respectively, wherein one or more of said VH CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 91, 92 and 93. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 94, 95 and 96 respectively, wherein one or more of said VL CDR sequences mayoptionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 94, 95 and 96. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 91, 92 and 93 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ IDNOs: 94, 95 and 96 respectively, wherein one or more of said CDR sequences may optionally have from 1to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one ofSEQ ID NOs: 91 to 96.In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 229 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 230 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 280 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 99 and / or a VL CDR3 sequence set forth in SEQ ID NO: 102, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 97, 98 and 99 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 97, 98 and 99. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 100, 101 and 102 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 100, 101 and 102. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 97, 98 and 99 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 100, 101 and 102 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 97 to 102. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 231 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 232 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 281 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 105 and / or a VL CDR3 sequence set forth in SEQ ID NO: 108, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 103, 104 and 105 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 103, 104 and 105. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 106, 107 and 108 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 106, 107 and 108. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 103, 104 and 105 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 106, 107 and 108 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared toone of SEQ ID NOs: 103 to 108. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 233 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 234 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto).In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 282 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 111 and / or a VL CDR3 sequence set forth in SEQ ID NO: 114, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR.In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 109, 110 and 111 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 109, 110 and 111. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 112, 113 and 114 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 112, 113 and 114. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 109, 110 and 111 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 112, 113 and 114 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 109 to 114. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 235 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 236 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 283 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto).In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 117 and / or a VL CDR3 sequence set forth in SEQ ID NO: 120, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 115, 116 and 117 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 115, 116 and 117. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 118, 119 and 120 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 118, 119 and 120. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 115, 116 and 117 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 118, 119 and 120 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 115 to 120. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 237 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 238 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 284 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 123 and / or a VL CDR3 sequence set forth in SEQ ID NO: 126, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 121, 122 and 123 respectively, wherein one or more of said VH CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 124, 125 and 126. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 121, 122 and 123 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 121, 122 and 123. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 124, 125 and 126 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 124, 125 and 126 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 121 to 126. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 239 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 240 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 285 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 129 and / or a VL CDR3 sequence set forth in SEQ ID NO: 132, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 127, 128 and 129 respectively, wherein one or more of said VH CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 127, 128 and 129.In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 130, 131 and 132 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 130, 131 and 132. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 127, 128 and 129 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 130, 131 and 132 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared toone of SEQ ID NOs: 127 to 132. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 241 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 242 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 286 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 135 and / or a VL CDR3 sequence set forth in SEQ ID NO: 138, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications(e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 133, 134 and 135 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 133, 134 and 135.In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 136, 137 and 138 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 136, 137 and 138. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 133, 134 and 135 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 136, 137 and 138 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared toone of SEQ ID NOs: 133 to 138.In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 243 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 244 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 287 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 141 and / or a VL CDR3 sequence set forth in SEQ ID NO: 144, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 139, 140 and 141 respectively, wherein one or more of said VH CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 139, 140 and 141. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 142, 143 and 144 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 142, 143 and 144. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 139, 140 and 141 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 142, 143 and 144 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 139 to 144. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 245 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 246 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 288 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 147 and / or a VL CDR3 sequence set forth in SEQ ID NO: 150, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 145, 146 and 147 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 145, 146 and 147. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 148, 149 and 150 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 148, 149 and 150. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 145, 146 and 147 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 148, 149 and 150 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 145 to 150. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 247 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 248 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 289 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 153 and / or a VL CDR3 sequence set forth in SEQ ID NO: 156, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 151, 152 and 153 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 151, 152 and 153. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 154, 155 and 156 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 154, 155 and 156.In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 151, 152 and 153 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 154, 155 and 156 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 151 to 156. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 249 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 250 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 290 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 159 and / or a VL CDR3 sequence set forth in SEQ ID NO: 162, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 157, 158 and 159 respectively, wherein one or more of said VH CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g.substitutions) compared to one of SEQ ID NOs: 157, 158 and 159. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 160, 161 and 162 respectively, wherein one or more of said VL CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 160, 161 and 162. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 157, 158 and 159 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 160, 161 and 162 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared toone of SEQ ID NOs: 157 to 162.In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 251 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 252 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 291 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 165 and / or a VL CDR3 sequence set forth in SEQ ID NO: 168, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR.In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 163, 164 and 165 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 163, 164 and 165. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 166, 167 and 168 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g.substitutions) compared to one of SEQ ID NOs: 166, 167 and 168. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 163, 164 and 165 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 166, 167 and 168 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 163 to 168. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 253 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 254 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 292 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 171 and / or a VL CDR3 sequence set forth in SEQ ID NO: 174, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 169, 170 and 171 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 169, 170 and 171. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 172, 173 and 174 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 127, 173 and 174. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 169, 170 and 171 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 172, 173 and 174 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 169 to 174. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 255 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 256 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 293 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 177 and / or a VL CDR3 sequence set forth in SEQ ID NO: 180, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 175, 176 and 177 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 175, 176 and 177. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 178, 179 and 180 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 178, 179 and 180. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 175, 176 and 177 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 178, 179 and 180 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 175 to 180. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 257 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequence set forth in SEQ ID NO: 258 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 294 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 183 and / or a VL CDR3 sequence set forth in SEQ ID NO: 186, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 181, 182 and 183 respectively, wherein one or more of said VH CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 181, 182 and 183. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 184, 185 and 186 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g.substitutions) compared to one of SEQ ID NOs: 184, 185 and 186.In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 181, 182 and 183 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 184, 185 and 186 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 181 to 186. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising the sequence set forth in SEQ ID NO: 259 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 260 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 295 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto. In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forth in SEQ ID NO: 189 and / or a VL CDR3 sequence set forth in SEQ ID NO: 192, wherein the aforementioned CDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 187, 188 and 189 respectively, wherein one or more of said VH CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 187, 188 and 189. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 190, 191 and 192 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 190, 191 and 192. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 187, 188 and 189 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 190, 191 and 192 respectively, wherein one or more of said CDR sequences may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 187 to 192.In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 261 or a sequence having at least 70% identity thereto (optionally at least 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 262 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 296 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto. In an embodiment, the antigen recognition domain of the CAR comprises a VH CDR3 sequence set forthin SEQ ID NO: 195 and / or a VL CDR3 sequence set forth in SEQ ID NO: 198, wherein the aforementionedCDR sequence may optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to the aforementioned CDR. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 193, 194 and 195 respectively, wherein one or more of said VH CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 193, 194 and 195. In an embodiment, the antigen recognition domain of the CAR comprises VL CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 196, 197 and 198 respectively, wherein one or more of said VL CDR sequencesmay optionally have from 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 196, 197 and 198. In an embodiment, the antigen recognition domain of the CAR comprises VH CDR1, 2 and 3 sequencesset forth in SEQ ID NOs: 193, 194 and 195 respectively, and VL CDR1, 2 and 3 sequences set forth in SEQID NOs: 196, 197 and 198 respectively, wherein one or more of said CDR sequences may optionally havefrom 1 to 3, more particularly 1 or 2 amino acid sequence modifications (e.g. substitutions) compared to one of SEQ ID NOs: 193 to 198. In an embodiment, the antigen recognition domain of the CAR comprises a VH domain comprising thesequence set forth in SEQ ID NO: 263 or a sequence having at least 70% identity thereto (optionally atleast 80% or at least 90% or at least 95% identity thereto) and / or a VL domain comprising the sequenceset forth in SEQ ID NO: 264 or a sequence having at least 70% identity thereto (optionally at least 80% orat least 90% or at least 95% identity thereto). In an embodiment, the antigen recognition domain of the CAR comprises, consists essentially of or consistsof the sequence set forth in SEQ ID NO: 297 or a sequence having at least 70% identity thereto (optionallyat least 80% or at least 90% or at least 95% identity thereto. Where a CDR does contain an amino acid sequence modification, this may be a deletion, addition, or substitution of an amino acid residue of the CDR sequence as set out in the above-mentioned SEQ ID NOs. More particularly, the modification may be an amino acid substitution, for example a conservative amino acid substitution, e.g., as set out above. A longer CDR may tolerate more amino acid residue modifications. In the case of CDRs which are 5 or more, or 7 or more, amino acid residues long, the modifications may be of 0, 1, 2 or 3 residues, e.g. 2 residues. In general, there may be 0, 1, 2, or 3 modifications to any particular CDR sequence. Further, in an embodiment, CDRs 1 and 2 may be modified, and CDR3 may be unmodified. In another embodiment all 3 CDRs may be modified. In another embodiment, the CDRs are not modified. The antigen binding domain may be in the form of a scFv comprising the VH and VL domain sequences as set out above, in either order, for example VH-VL. The VH and VL sequences may be linked by a linker sequence. Suitable linkers can be readily selected and can be of any of a suitable length, such as from 1 amino acid (e.g. Gly) to 30 amino acids, e.g. from any one of 2, 3, 4, 5, 6, 7,8, 9, or 10 amino acids to any one of 12, 15, 18, 20, 21, 25, 30 amino acids, for example, 5-30, 5-25, 6-25, 10-15, 12-25, 15 to 25 etc. Exemplary linkers include glycine polymers (G), glycine-serine polymers, glycine-alanine polymers, alanine-serine polymers, and other flexible linkers known in the art, as discussed above. The linker may comprise 1 or more “GS” domains as discussed above.The linker sequence may be a flexible linker sequence. Flexible linkers are a category of linker sequenceswell known and described in the art. Linker sequences are generally known as sequences which may be used to link, or join together, proteins or protein domains, to create for example fusion proteins or chimeric proteins, or multifunctional proteins or polypeptides. They can have different characteristics, and forexample may be flexible, rigid or cleavable. Protein linkers are reviewed for example in Chen et al., 2013,Advanced Drug Delivery Reviews 65, 1357-1369, which compares the category of flexible linkers with those of rigid and cleavable linkers. Flexible linkers are also described in Klein et al., 2014, Protein Engineering Design and Selection, 27(10), 325-330; van Rosmalen et al., 2017, Biochemistry, 56,6565-6574; andChichili et al., 2013, Protein Science, 22, 153-167.A flexible linker is a linker which allows a degree of movement between the domains, or components, whichare linked. They are generally composed of small non-polar (e.g. Gly) or polar (e.g. Ser or Thr) amino acidresidues. The small size of the amino acids provides flexibility and allows for mobility of the connected parts(domains or components). The incorporation of polar amino acids can maintain the stability of the linker in aqueous environments by forming hydrogen bonds with water molecules. The most commonly used flexible linkers have sequences primarily composed of Ser and Gly residues (so-called “GS linkers”). However, many other flexible linkers have also been described (see Chen et al,.2013,supra, for example), which may contain additional amino acids such as Thr and / or Ala, and / or Lys and / orGlu which may improve solubility. Any flexible linker known and reported in the art may be used.Although the length of the linker is not critical, it may in some embodiments be desirable to have a shorter linker sequence. For example, the linker sequence may have a length of no more than 25, preferably no more than 24, 23, 22 or 21 amino acids. In other embodiments, a longer linker sequence may be desired, for example composed of, or comprising, multiple repeats of a GS domain. In some embodiments the linker may be from any one of 2, 3, 4, 5 or 6 to any one of 24, 23, 22 or 21 amino acids in length. In other embodiments it may be from any one of 2, 3, 4, 5 or 6 to any one of 21, 20, 19, 18, 17, 16, or 15 amino acids in length. In other embodiments it may be intermediate between these ranges, from example from 6 to 21, 6 to 20, 7 to 20, 8-20, 9-20, 10-20, 8-18, 9-18, 10-18, 9-17, 10-17, 9-16, 10-16 etc. It may accordingly be in a range made up from any of the integers listed above. The use of GS linkers, or more particularly GS (“Gly-Ser”) domains in linkers, may allow the length of the linker readily to be varied by varying the number of GS domain repeats, and so such linkers represent onepreferred class of linkers. However, flexible linkers are not limited to those based on “GS” repeats, andother linkers comprising Ser and Gly residues dispersed throughout the linker sequence have beenreported, including in Chen et al., supra.Accordingly, in one embodiment the linker sequence may comprise at least 40% Gly or Gly and Ser residues. In another embodiment, the linker sequence may comprise Ser and / or Gly residues, and no more than 15 other amino acid residues, preferably no more than 14, 13, 12, 11, 10, 9, 8, 6, 7, 5, or 4 other amino acidresidues. It will be understood than an “other” amino acid residue may be any amino acid which is not Seror Gly. Pro residues in linkers tend to confer rigidity and so in one embodiment the linker sequence does not comprise any Pro residues. However, this is not absolute, as depending on the sequence context, a flexible linker sequence may contain one or more Pro residues. In one preferred embodiment, the linker sequence comprises at least one Gly-Ser domain composed solely of Ser and Gly residues. In such an embodiment, the linker may contain no more than 15 other amino acid residues, preferably no more than 14, 13, 12, 11, 10, 9, 8, 6, 7, 5, or 4 other amino acid residues. The Gly-Ser domain may have the formula: (S)q-[(G)m-(S)m]n-(G)p wherein q is 0 or 1; m is an integer from 1-8; n is an integer of at least 1 (e.g. from 1 to 8, or more particularly 1 to 6); and p is 0 or an integer from 1 to 3. More particularly, the Gly-Ser domain may have the formula: (i) S-[(G)m-S]n; (ii) [(G)m-S]n; or (iii) [(G)m-S]n-(G)p wherein m is an integer from 2-8 (for example 3-4); n is an integer of at least 1 (for example from 1 to 8, or more particularly 1 to 6); and p is 0 or an integer from 1 to 3. In a representative example, the Gly-Ser domain may have the formula: S-[G-G-G-G-S]n wherein n is an integer of at least one (preferably 1 to 8, or 1-6, 1-5, 1-4, or 1-3). In the formula above, the sequence GGGGS is SEQ ID NO: 377. A representative sequence GGGS is shown in SEQ ID NO: 374. A linker sequence may be composed solely of, or may consist of, one or more Gly-Ser domains as described or defined above. However, as noted above, in another embodiment, the linker sequence maycomprise one or more Gly-Ser domains, and additional amino acids. The additional amino acids may be atone or both ends of a Gly-Ser domain, or at one or both ends of a stretch of repeating Gly-Ser domains. Thus, the additional amino acid, which may be other amino acids, may lie at one or both ends of the linker sequence, e.g. they may flank the Gly-Ser domain(s). In other embodiments, the additional amino acids may lie between Gly-Ser domains. For example, two Gly-Ser domains may flank a stretch of other amino acids in the linker sequence. Further, as also noted above, in other linkers, GS domains need not be repeated, and G and / or S residues, or a short domain such as GS, may simply be distributed along the length or the sequence. Representative exemplary linker sequences are listed below: ETSGGGGSRL (SEQ ID NO: 375) SGGGGSGGGGSGGGGS ((SEQ ID NO: 376) S(GGGGS)1-5 (where GGGGS is SEQ ID NO: 377) (GGGGS)1-5 (where GGGGS is SEQ ID NO: 377) S(GGGS)1-5 (where GGGS is SEQ ID NO: 374) (GGGS)1-5 (where GGGS is SEQ ID NO: 374) S(GGGGGS)1-5 (where GGGGGS is SEQ ID NO: 378) (GGGGGS)1-5 (where GGGGGS is SEQ ID NO: 378) S(GGGGGGS)1-5 (where GGGGGGS is SEQ ID NO: 379) (GGGGGGS)1-5 (where GGGGGGS is SEQ ID NO: 379)GGGGSGGGGSGGGGS (SEQ ID NO: 380)GGGGG (SEQ ID NO: 381)GGGGSGGGGS (SEQ ID NO: 382)GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 383) GGGGGG (SEQ ID NO: 384) G6 (SEQ ID NO: 385) G8(SEQ ID NO: 386)KESGSVSSEQLAQFRSLD (SEQ ID NO: 387)EGKSSGSGSESKST (SEQ ID NO: 388) GSAGSAAGSGEF (SEQ ID NO: 389)SGGGGSAGSAAGSGEF (SEQ ID NO: 390)SGGGLLLLLLLLGGGS (SEQ ID NO: 391) SGGGAAAAAAAAGGGS (SEQ ID NO: 392) SGGGAAAAAAAAAAAAAAAAGGGS (SEQ ID NO: 393) SGALGGLALAGLLLAGLGLGAAGS (SEQ ID NO: 394) SLSLSPGGGGGPAR (SEQ ID NO: 395) SLSLSPGGGGGPARSLSLSPGGGGG (SEQ ID NO: 396) GSSGSS (SEQ ID NO: 397) GSSSSSS (SEQ ID NO: 398) GGSSSS (SEQ ID NO: 399)GSSSSS (SEQ ID NO: 400)SGGGGS (SEQ ID NO: 401). In certain embodiments, the linker has the sequence (GGGGS)3 (SEQ ID NO: 380). Although the linker sequences of the polypeptides of the invention, as defined above, are flexible sequences, the present disclosure includes also other polypeptides, including those which comprise linkers which are not flexible, and / or which do not meet the definitions and requirements set out above.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 199 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 200. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 201 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 202. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 203 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 204. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 205 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 206. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 207 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 208.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequence as set forth in SEQ ID NO: 209 linked via a linker of sequence (X)n, where X is any amino acid and n is an integer of between 15 and 25, to the VL sequence of SEQ ID NO: 210. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 211 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 212. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 213 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 214. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 215 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 216. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 217 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 218. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 219 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 220. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 221 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 222. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 223 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 224.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 225 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 226. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 227 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 228. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequence as set forth in SEQ ID NO: 229 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 230.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 231 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 232. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 233 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 234.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 235 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 236.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 237 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 238. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 239 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 240. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 241 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 242. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 243 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 244. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 245 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 246.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 247 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 248. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 249 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 250. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 251 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 252. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 253 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 254. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 255 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 256.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 257 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 258.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 259 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 260. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 261 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 262. Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 263 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 264.Accordingly in one embodiment the antigen binding domain may comprise, or consist of, a VH sequenceas set forth in SEQ ID NO: 265 linked via a linker of sequence (X)n, where X is any amino acid and n is aninteger of between 15 and 25, to the VL sequence of SEQ ID NO: 266. In further embodiments, the CAR may comprise or consist of a sequence set forth in any of SEQ ID NOs:298 to 363, or a variant thereof, e.g. a sequence having at least 70% identity thereto, optionally at least80% or at least 90% or at least 95% identity thereto. The variant sequences disclosed and described herein, including the variant CAR, VH, VL and antigen binding domain sequences, may have at least 75, 80, 85, 90, 92, 95, 96, 97, 98, or 99% sequence identity to the specified SEQ ID NOs. The CAR also preferably comprises a hinge domain to hold the extracellular domain, particularly the antigenbinding domain, away from the cell surface, and further comprises a transmembrane domain. The hingeand transmembrane domains may comprise the hinge and transmembrane sequences from any protein which has a hinge domain and / or a transmembrane domain, including any of the type I, type II or type III transmembrane proteins. The hinge domain may be selected from the hinge regions of CD28, CD8alpha, CD4, CD7, CH2CH3, an immunoglobulin, or a part or variant thereof. Typically, the hinge may be derived from CD8, particularly, CD8alpha, or from CH2CH3. In one embodiment, the hinge may comprise one or more cysteine residues e.g., to allow disulphide bonding. For example, the CD8 hinge may comprise one or more cysteine residues e.g., one cysteine residue, two cysteine residues or three cysteine residues. The transmembrane domain of the CAR may also comprise an artificial hydrophobic sequence. The transmembrane domains of the CAR may be selected so as not to dimerize. Additional transmembrane domains will be apparent to those of skill in the art. Examples of transmembrane (TM) regions used in CAR constructs are: 1) The CD28 TM region (Pule et al, Mol Ther, 2005, Nov;12(5):933-41; Brentjens et al, CCR, 2007, Sep 15;13(18 Pt 1):5426-35; Casucci et al, Blood, 2013, Nov 14;122(20):3461-72.); 2) The OX40 TMregion (Pule et al, Mol Ther, 2005, Nov;12(5):933-41); 3) The 4-1BB TM region (Brentjens et al, CCR, 2007,Sep 15;13(18 Pt 1):5426-35); 4). The CD3 zeta TM region (Pule et al, Mol Ther, 2005, Nov;12(5):933-41; Savoldo B, Blood, 2009, Jun 18;113(25):6392-402.); 5) The CD8α TM region (Maher et al, Nat Biotechnol, 2002, Jan;20(1):70-5.; Imai C, Leukemia, 2004, Apr;18(4):676-84; Brentjens et al, CCR, 2007, Sep 15;13(18 Pt 1):5426-35; Milone et al, Mol Ther, 2009, Aug;17(8):1453-64.). Other transmembrane domains which may be used include those from ICOS, CD4, CD45, CD9, CD16, CD22, CD33, CD64, CD80, CD86, or CD154. Preferably, the transmembrane domain may be derived from CD28, or CD8α. In one embodiment, the CAR may not comprise a dimerisation domain which binds to a regulating molecule.A regulating molecule is any molecule that can bind to at least one dimerisation domain in a CAR and canprevent the interaction, or cause the interaction, of a pair of dimerisation domains. Examples of regulating molecules include soluble proteins (e.g., cytokines, TGF-beta, VEGF) or small molecules. In a further embodiment, when dimerisation with other CAR molecules occurs, it may not be controlled. In another embodiment, monovalent binding of the CAR to an antigen may allow activation of the cell in which the CAR is expressed. A hinge domain may conveniently be obtained from the same protein as the transmembrane domain. In one embodiment, where the transmembrane domain is derived from the CD8α transmembrane domain, the hinge domain is derived from the CD8α hinge domain. Alternatively, the hinge domain may be obtained from a different protein to the transmembrane domain. For example, the hinge domain may be derived from the CH2CH3 hinge domain and the transmembrane domain may be derived from the CD28 transmembrane domain. For example, the hinge domain may be derived from the CD8α hinge domain and may comprise the amino acid sequence shown in SEQ ID NO: 402, or a variant thereof which is at least 80% identical to SEQ ID NO; 402. Suitably, the variant may be at least 85, 90, 95, 97, 98 or 99% identical to SEQ ID NO: 402. An example of a modified CD8α hinge domain is shown in SEQ ID NO: 403. For example, the transmembrane domain may be derived from the CD8α transmembrane domain and maycomprise the amino acid sequence shown as SEQ ID NO: 404 which represents amino acids 183 to 203of human CD8α, or a variant which is at least 80% identical to SEQ ID NO: 404. Suitably, the variant may be at least 85, 90, 95, 97, 98 or 99% identical to SEQ ID NO: 404. The CD8α transmembrane domain may be combined with a CD8α hinge domain. In an embodiment, the CAR comprises a combined CD8α hinge and transmembrane domain sequence as shown in SEQ ID NO.405 or SEQ ID NO: 407, or a variant thereof which has at least 80% sequence identity thereto. The variantmay be at least 85, 90, 95, 97, 98 or 99% identical to SEQ ID NO: 405 or SEQ ID NO: 407 respectively.SEQ ID NO. 405 comprises a modified hinge domain comprising 2 amino acid modifications of cysteineresidues relative to the wild-type CD8α hinge sequence. The modified CD8α hinge domain sequence is shown in SEQ ID NO.403. The wildtype CD8α hinge and transmembrane domain sequence is shown inSEQ ID NO.407. The 6 amino acids at the end of SEQ ID NO.405 and 407, when present, are not locatedin the membrane and form part of the endodomain of the CAR. A variant of such hinge sequences havingat least 80% sequence identity to SEQ ID NO.405 or 407 may be used.For example, the hinge domain may be derived from the CH2CH3 hinge domain and may comprise thesequence shown in SEQ ID NO.408 or SEQ ID NO.409 or a variant thereof which is at least 80% identicalto SEQ ID NO. 408 or 409 respectively. The variant may be at least 85, 90, 95, 97, 98 or 99% identical toSEQ ID NO. 408 or 409 respectively.Alternatively, an example of a CD28 hinge and transmembrane sequence which may be used is SEQ IDNO: 410 or a variant thereof which is at least 80% identical to SEQ ID NO: 410. The variant may be at least85, 90, 95, 97, 98 or 99% identical to SEQ ID NO: 410. By way of further example, the CAR may comprise a native or modified CD8α hinge domain and a CD28 transmembrane domain, or a CD28 hinge domain and CD8α transmembrane domain, for example based on the sequences given above. In one embodiment, a CH2CH3 hinge sequence comprising one or more cysteine residues may be used. For example, a CH2CH3 hinge sequence comprising one, two, three, four or more cysteine residues. Other hinge domains which may be used include those from CD4, CD7, or an immunoglobulin, or a part or variantthereof. These hinge domains may comprise one or more cysteine residues, for example one, two, three,four or more cysteine residues. The CAR may further comprise a signal (or alternatively termed, leader) sequence which targets it to theendoplasmic reticulum pathway for expression on the cell surface. An illustrative signal / leader sequenceis MALPVTALLLPLALLLHAAAP as shown in SEQ ID NO. 411. This comprises a single amino acidsubstitution compared to the wild type CD8α sequence MALPVTALLLPLALLLHAARP as shown in SEQ IDNO.412. Either sequence, or a variant sequence having at least 70% sequence identity thereto may beused. For example, a variant sequence may have at least 75, 80, 85, 90, 95, 97, 98 or 99% sequenceidentity thereto. The endodomain of a CAR as described herein comprises motifs necessary to transduce the effector function signal and direct a cell expressing the CAR to perform its specialized function upon antigen binding. Particularly, the endodomain may comprise one or more (e.g. two or three) Immunoreceptor tyrosine-basedactivation motifs (ITAMs), typically comprising the amino acid sequence of YXXL / I, where X can be anyamino acid. Examples of intracellular signaling domains include, but are not limited to, ζ chain endodomainof the T-cell receptor or any of its homologs (e.g., η chain, FcεR1γ and β chains, MB1 (Igα) chain, B29 (Igβ) chain, etc.), CD3 polypeptide domains (∆, δ and ε), syk family tyrosine kinases (Syk, ZAP 70, etc.), src family tyrosine kinases (Lck, Fyn, Lyn, etc.) and other molecules involved in T-cell transduction, such asCD2, CD5 and CD28. The intracellular signaling domain may comprise human CD3 zeta chainendodomain, FcyRIII, FcsRI, cytoplasmic tails of Fc receptors, immunoreceptor tyrosine-based activation motif (ITAM) bearing cytoplasmic receptors or combinations thereof. Commonly, the intracellular signaling domain comprises the intracellular signaling domain of a human CD3 zeta chain. The sequence of the intracellular signaling domain of human CD3 zeta chain is set out in SEQ ID NO.413. The CAR may comprise a CD3ζ signalling domain comprising or consisting of a sequence asset out in SEQ ID NO. 413 or a sequence having at least 80, 85, 90, 95, 97, 98 or 99% identity to SEQ IDNO: 413. In an embodiment the signaling domain comprises or consists of SEQ ID NO.413. Other signaling domains which may be used include the signaling domains of CD28 or CD27 or variants thereof. Additional intracellular signaling domains will be apparent to those of skill in the art and may beused in connection with alternate embodiments of the invention. In one embodiment, the present CAR maynot comprise a costimulatory domain derived from 4-1BB within the endodomain. The present CAR may comprise a compound endodomain comprising a fusion of the intracellular part of aT-cell co-stimulatory molecule to that of e.g. CD3ζ. Such a compound endodomain may be referred to asa second-generation CAR which can transmit an activating and co-stimulatory signal simultaneously afterantigen recognition. The co-stimulatory domain most commonly used is that of CD28. This supplies themost potent co-stimulatory signal - namely immunological signal 2, which triggers T-cell proliferation. TheCAR endodomain may also comprise one or more TNF receptor family signalling domain, such as the signalling domain of ICOS, (CD134) OX40, 4-1BB, CD27 or TNFRSF25, or a part or variant thereof, although preferably the CAR may not comprise an endodomain comprising the signalling domains of both CD28 and 4-1BB. An intracellular signaling domain of CD28 which may be used as a co-stimulatory domain is shown in SEQ ID NO.415. Illustrative sequences for OX40, 4-1BB, ICOS and TNFRSF25 signalling domains are shownin SEQ ID NO: 416 to 419. The CAR may comprise one or more co-stimulatory domains comprising or consisting of the sequence of any one of SEQ ID NO: 415, 416, 417, 418 and 419, or a variant thereofhaving at least 80, 85, 90, 95, 97, 98 or 99% sequence identity thereto.In certain embodiments, the transmembrane domain and the intracellular signalling domain derived from a T-cell co-stimulatory molecule may be derived from the same protein. For example, in certain embodiments, the transmembrane domain and intracellular signalling domain derived from a T-cell co-stimulatorymolecule may be derived from CD28. For example, the CAR may comprise a combined CD28transmembrane and CD28 intracellular signalling domain as shown in SEQ ID NO: 414, or a variant thereof having at least 80% sequence identity thereto. The variant may be at least 85, 90, 95, 97, 98 or 99% identical to SEQ ID NO: 414. In one embodiment, the CAR comprises a human CD8 hinge domain or a variant thereof and a human CD8 transmembrane domain. Alternatively, or additionally, the CAR comprises an endodomain comprising,consisting essentially of or consisting of a human CD28 co-stimulatory domain and a human CD3 zetasignalling domain. In one preferred embodiment the CAR comprises a hinge, transmembrane, and intracellular (or endo) domains as follows: (i) a CH2CH3 hinge sequence comprising or consisting of the sequence as set forth inSEQ ID NO. 418 or SEQ ID NO. 419, or a sequence having at least 80% sequenceidentity thereto; (ii) a CD28 transmembrane and co-stimulatory domain comprising or consisting of thesequence as set forth in SEQ ID NO.414, or a sequence having at least 80% sequence identity thereto; (iii) a CD3ζ signalling domain comprising or consisting of the sequence as set forth in SEQID NO.413, or a sequence having at least 80% sequence identity thereto. In an alternative preferred embodiment the CAR comprises a hinge, transmembrane, and intracellular (or endo) domains as follows: (i) a CD8α hinge and transmembrane domain sequence comprising or consisting of the sequenceas set forth in SEQ ID NO.405 or 407, or a sequence having at least 80% sequence identity thereto; (ii) a CD28 co-stimulatory domain comprising or consisting of the sequence as set forth SEQ IDNO.415, or a sequence having at least 80% sequence identity thereto; (iii) a CD3ζ signalling domain comprising or consisting of the sequence as set forth in SEQ ID NO.413, or a sequence having at least 80% sequence identity thereto. The CAR, as encoded and expressed, may further comprise a leader sequence comprising or consistingof a sequence as set out in SEQ ID NO. 411 or SEQ ID NO: 412, or a sequence having at least 80%sequence identity thereto. The antigen binding domain of the CAR may comprise or consist of a sequence as set out in any one ofSEQ ID NOs: 265 to 297 or a sequence having at least 70% or at least 80% or at least 90% or at least 95%sequence identity thereto which is capable of binding to ASGPR. In particular, the antigen binding domainof the CAR may comprise or consist of a sequence as set out in SEQ ID NO. 267 or 268 or a sequencehaving at least 80% sequence identity thereto. In particular, the antigen binding domain of the CAR maycomprise one or more (e.g. all) of the CDRs set out in SEQ ID NOs. 13 to 18 or a sequence having from 1to 3 amino acid modifications compared to one of SEQ ID NOs 13 to 18. In particular, the antigen bindingdomain of the CAR may comprise one or more (e.g. all) of the CDRs set out in SEQ ID NOs. 19 to 24 or asequence having from 1 to 3 amino acid modifications compared to one of SEQ ID NOs 19 to 24.The antigen recognition domain variants described herein retain antigen-binding ability. For example, the variants may be capable of binding ASGPR to at least 10%, at least 20%, at least 30%, at least 40%, atleast 50%, at least 60%, at least 70%, at least 80% or at least 90% of the level of the correspondingreference amino acid sequence. The variant may be capable of binding ASGPR to a similar or the same level as the corresponding reference amino acid sequence or may be capable of binding ASGPR to a greater level than the corresponding reference amino acid sequence (e.g. increased by at least 10%, at least 20%, at least 30%, at least 40% or at least 50%). Although a CAR of the invention may comprise more than one antigen recognition domain, i.e. may bind to more than one liver specific antigen, or more than one epitope within a liver specific antigen as defined above, for example, as part of a dual or two polypeptide CAR system, in a particular embodiment, the CAR of the invention may comprise only one or a single antigen recognition domain. Thus, in its entirety one preferred representative CAR may comprise: i.a leader sequence comprising or consisting of a sequence as set out in SEQ ID NO. 411 or412, or a sequence having at least 80% sequence identity thereto; ii.an antigen binding domain comprising or consisting of a sequence as set out in any of SEQ ID NOs: 265 to 297 or a sequence having at least 80% sequence identity thereto;iii.a CH2CH3 hinge sequence comprising or consisting of the sequence as set forth in SEQ ID NO.408 or 409, or a sequence having at least 80% sequence identity thereto; iv.a CD28 transmembrane and co-stimulatory domain comprising or consisting of the sequence as set forth in SEQ ID NO.414, or a sequence having at least 80% sequence identity thereto; v.a CD3ζ signalling domain comprising or consisting of the sequence as set forth in SEQ ID NO. 413, or a sequence having at least 80% sequence identity thereto.An alternative preferred representative CAR may comprise: i.a leader sequence comprising or consisting of a sequence as set out in SEQ ID NO. 411 or412, or a sequence having at least 80% sequence identity thereto; ii.an antigen binding domain comprising or consisting of a sequence as set out in any of SEQ ID NOs: 265 to 297 or a sequence having at least 80% sequence identity thereto;iii.a CD8 hinge and transmembrane domain sequence comprising or consisting of the sequence as set forth in SEQ ID NO. 405 or 407, or a sequence having at least 80% sequence identitythereto; iv.a CD28 co-stimulatory domain comprising or consisting of the sequence as set forth in SEQ ID NO. 415, or a sequence having at least 80% sequence identity thereto;v.a CD3ζ signalling domain comprising or consisting of the sequence as set forth in SEQ ID NO. 413, or a sequence having at least 80% sequence identity thereto. The CAR of the present invention may comprise, or consist of, any one or more of the sequences as setout in SEQ ID NOs.298 to 363, or a variant thereof having at least about 70% identity thereto. For example,any variant may have at least about 75, 80, 85, 90, 95, 97, 98 or 99% identity to SEQ ID NOs 298 to 363. The CARs of SEQ ID NOs 298 to 363, or variants thereof, may further comprise a signal sequence, forexample a signal sequence having the sequence set out in SEQ ID NO: 411 or 412. In certain embodiments,the CAR of the present invention may comprise, or consist of, the sequence set forth in SEQ ID NO: 300 or SEQ ID NO: 301. These CARs may further comprise a signal sequence, for example a signal sequencehaving the sequence set out in SEQ ID NO: 411 or 412.The CAR of the present invention may comprise or consist of a sequence encoded by the sequence setforth in any of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence having at least about 70%identity to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443 respectively. For example,the CAR of the present invention may comprise or consist of a sequence encoded by the sequence setforth in any of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence having at least about 75, 80, 85, 90, 95, 97, 98 or 99% identity to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443respectively. The CAR of variants thereof may further comprise a signal sequence for example a signalsequence having the sequence set out in SEQ ID NO: 411 or 412. In certain embodiments, the CAR may comprise or consist of the sequence encoded by SEQ ID NO: 438 or SEQ ID NO: 439. These CARs may further comprise a signal sequence, for example a signal sequence having the sequence set out in SEQ ID NO: 411 or 412. The nucleic acid molecule encoded the CAR of the present invention may therefore comprise the sequenceset forth in any of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence encoding a CAR having atleast about 70% identity to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443 respectively. For example, the nucleic acid molecule may comprise the sequence set forth in any of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence encoding a CAR having at least about 75, 80, 85,90, 95, 97, 98 or 99% identity to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443respectively. In certain embodiments, the nucleic acid molecule may comprise the sequence set forth in SEQ ID NO: 438 or SEQ ID NO: 439. The CAR is capable of binding to ASGPR and of transducing a signal into a cell in which it isexpressed. Particularly, the CAR may be capable of binding to human and murine ASGPR and oftransducing a signal into a cell in which it is expressed. For example, the CAR may be capable of binding to human and murine ASGPR1 and / or ASGPR2 and of transducing a signal into a cell in which it is expressed. The cell may express only one type of CAR, i.e., where the cell expresses more than one CAR molecule,the amino acid sequences of each of these expressed molecules are identical to one another. Thus, theexpression construct and / or nucleic acid molecule described herein may encode only one type of CAR. As mentioned above, the cell or cell population of the invention may further comprise additional polypeptides, particularly exogenous polypeptides, such as a FOXP3 and / or safety switch polypeptide. The polypeptides of the present invention, e.g., the CAR, FOXP3 and safety switch, may be encoded by a single nucleic acid molecule. The nucleic acid molecule may comprise nucleotide sequences encoding self- cleavage sequences in between the encoded polypeptides, allowing the polypeptides to be expressed and / or produced as separate, or discrete components. By this it is meant that, although the polypeptides are encoded by a single nucleic acid molecule, through “cleavage” during or after translation at the encoded cleavage sites, they may be expressed or produced as separate polypeptides, and thus at the end of theprotein production process in the cell, they may be present in the cell as separate entities, or separatepolypeptide chains. Alternatively, additional exogenous polypeptides may be encoded by separate nucleicacid molecules or vectors. By “discrete” or “separate” polypeptides it is meant that the polypeptides are not linked to one another and are physically distinct. Indeed, following expression, they are located in different, or separate cellular locations. The CAR, FOXP3 and safety switch polypeptide are thus ultimately expressed as single andseparate components. The CAR is expressed as a cell surface molecule. The safety switch polypeptidemay be expressed inside a cell, or on the cell surface. In a particular embodiment, the safety switch polypeptide and the CAR are expressed on the surface of a cell which is intended for ACT. The FOXP3 is expressed inside the cell, where it can exert its effect as a transcription factor to regulate cell development and / or activity, as described further below. The safety switch polypeptide provides a cell in or on which it is expressed with a suicide moiety. This is useful as a safety mechanism which allows a cell which has been administered to a subject to be deleted should the need arise, or indeed more generally, according to desire or need, for example once a cell hasperformed or completed its therapeutic effect.A suicide moiety possesses an inducible capacity to lead to cellular death, or more generally to elimination or deletion of a cell. An example of a suicide moiety is a suicide protein, encoded by a suicide gene, which may be expressed in or on a cell alongside a desired transgene, in this case the CAR, which when expressed allows the cell to be deleted to turn off expression of the transgene (CAR). A suicide moiety herein is a suicide polypeptide that is a polypeptide that under permissive conditions, namely conditions that are induced or turned on, is able to cause the cell to be deleted. The suicide moiety may be a polypeptide, or amino acid sequence, which may be activated to perform acell-deleting activity by an activating agent which is administered to the subject, or which is active to performa cell-deleting activity in the presence of a substrate which may be administered to a subject. In a particular embodiment, the suicide moiety may represent a target for a separate cell-deleting agent which is administered to the subject. By binding to the suicide moiety, the cell-deleting agent may be targeted to the cell to be deleted. In particular, the suicide moiety may be recognised by an antibody, and binding of the antibody to the safety switch polypeptide, when expressed on the surface of a cell, causes the cell to be eliminated, or deleted. The suicide moiety may be HSV-TK or iCasp9. However, it is preferred for the suicide moiety to be, or to comprise, an epitope which is recognised by a cell-deleting antibody or other binding molecule capable of eliciting deletion of the cell. In such an embodiment, the safety switch polypeptide is expressed on the surface of a cell.The term “delete” as used herein in the context of cell deletion is synonymous with “remove” or “ablate” or“eliminate”. The term is used to encompass cell killing, or inhibition of cell proliferation, such that the number of cells in the subject may be reduced.100% complete removal may be desirable but may not necessarily be achieved. Reducing the number of cells, or inhibiting their proliferation, in the subject may be sufficient to have a beneficial effect. In particular, the suicide moiety may be a CD20 epitope which is recognised by the antibody Rituximab. Thus, in the safety switch polypeptide the suicide moiety may comprise a minimal epitope based on the epitope from CD20 that is recognised by the antibody Rituximab. Biosimilars for Rituximab are available and may be used. A person of skill in the art is readily able to use routine methods to prepare an antibody having the binding specificity of Rituximab using the available amino acid sequences therefor. CAR-cells specific for ASGPR, which also express a safety switch polypeptide comprising this sequence can be selectively killed using the antibody Rituximab, or an antibody having the binding specificity of Rituximab. The safety switch polypeptide is expressed on the cell surface and when the expressed polypeptide is exposed to or contacted with Rituximab, or an antibody with the same binding specificity, death of the cell ensues. Thus, Rituximab, or an antibody having the binding specificity thereof, may be provided for use in ACT in combination with a cell of the invention. The cell or nucleic acid or vector or construct for production of the cell and the Rituximab or equivalent antibody may be provided in a kit, or as a combination product. For example, the suicide constructs of WO2013 / 153391 or WO2021 / 239812 (both incorporated herein by reference) may be used in a cell or cell population (e.g., Treg or Treg population) as described herein. The nucleic acid molecule of the present invention may be designed to increase FOXP3 expression in cells (e.g., Tregs) by introducing into the cells a nucleotide sequence encoding FOXP3, which term issynonymous with the term “a FOXP3 polypeptide”. The nucleic acid molecule, and constructs and vectorscontaining it, thus provide a means for increasing FOXP3 in a cell, e.g., in a Treg or a CD4+ cell. As discussed above, a single nucleic acid molecule may encode the CAR of the invention and a FOXP3 polypeptide or the CAR and FOXP3 may be encoded by separate or discrete nucleic acid molecules. Thus, the invention provides a cell comprising a nucleic acid molecule comprising a nucleotide sequence encoding a CAR and a nucleic acid molecule comprising a nucleotide sequence encoding FOXP3, particularly a pluripotent cell (e.g. an iPSC), an HPC cell (e.g. expressing CD34), a CD4+ T cell or a Treg cell.“FOXP3” is the abbreviated name of the forkhead box P3 protein. FOXP3 is a member of the FOX proteinfamily of transcription factors and functions as a master regulator of the regulatory pathway in thedevelopment and function of regulatory T cells. “FOXP3” as used herein encompasses variants, isoforms,and functional fragments of FOXP3. “Increasing FOXP3 expression” means to increase the levels of FOXP3 mRNA and / or protein in a cell (or population of cells) in comparison to a corresponding cell which has not been modified (or population of cells) by introduction of the nucleic acid molecule, construct or vector. For example, the level of FOXP3 mRNA and / or protein in a cell modified according to the present invention (or a population of such cells) may be increased to at least 1.5-fold, at least 2-fold, at least 5-fold, at least 10-fold, at least 50-fold, at least 100-fold, at least 150-fold greater than the level in a corresponding cell which has not been modified according to the present invention (or population of such cells). Preferably the cell is a Treg or the population of cells is a population of Tregs. Suitably, the level of FOXP3 mRNA and / or protein in a modified cell (or a population of such cells) may be increased to at least 1.5-fold greater, 2-fold greater, or 5-fold greater than the level in a corresponding cell which has not been so modified (or population of such cells). Preferably the cell is a Treg or the population of cells is a population of Tregs. Techniques for measuring the levels of specific mRNA and protein are well known in the art. mRNA levelsin a population of cells, such as Tregs, may be measured by techniques such as the Affymetrix ebioscienceprime flow RNA assay, Northern blotting, serial analysis of gene expression (SAGE) or quantitativepolymerase chain reaction (qPCR). Protein levels in a population of cells may be measured by techniques such as flow cytometry, high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC / MS), Western blotting or enzyme-linked immunosorbent assay (ELISA). A “FOXP3 polypeptide” is a polypeptide having FOXP3 activity i.e., a polypeptide able to bind FOXP3 targetDNA and function as a transcription factor regulating development and function of Tregs. Particularly, aFOXP3 polypeptide may have the same or similar activity to wildtype FOXP3 (SEQ ID NO.423), e.g., may have at least 40, 50, 60, 70, 80, 90, 95, 100, 110, 120, 130, 140 or 150% of the activity of the wildtypeFOXP3 polypeptide. Thus, a FOXP3 polypeptide encoded by the nucleotide sequence in the nucleic acid,construct or vector described herein may have increased or decreased activity compared to wildtypeFOXP3. Techniques for measuring transcription factor activity are well known in the art. For example,transcription factor DNA-binding activity may be measured by ChIP. The transcription regulatory activity of a transcription factor may be measured by quantifying the level of expression of genes which it regulates. Gene expression may be quantified by measuring the levels of mRNA and / or protein produced from the gene using techniques such as Northern blotting, SAGE, qPCR, HPLC, LC / MS, Western blotting or ELISA. Genes regulated by FOXP3 include cytokines such as IL-2, IL-4 and IFN-γ (Siegler et al. Annu. Rev.Immunol. 2006, 24: 209-26, incorporated herein by reference). As discussed in detail below, FOXP3 or aFOXP3 polypeptide includes functional fragments, variants, and isoforms thereof, e.g., of SEQ ID NO. 423. A “functional fragment of FOXP3” may refer to a portion or region of a FOXP3 polypeptide or a polynucleotide (i.e., nucleotide sequence) encoding a FOXP3 polypeptide that has the same or similar activity to the full-length FOXP3 polypeptide or polynucleotide. The functional fragment may have at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the activity of the full-length FOXP3 polypeptide or polynucleotide. A person skilled in the art would be able to generate functional fragments based on the known structural and functional features of FOXP3. These are described, for instance, in Song, X., et al., 2012. Cell reports, 1(6), pp.665-675; Lopes, J.E., et al., 2006. The Journal of Immunology, 177(5), pp.3133-3142; and Lozano, T., et al, 2013. Frontiers in oncology, 3,p.294. Further, a N and C terminally truncated FOXP3 fragment is described within WO2019 / 241549(incorporated herein by reference), for example, having the sequence SEQ ID NO. 424 as discussedbelow. A “FOXP3 variant” may include an amino acid sequence or a nucleotide sequence which may be at least 50%, at least 55%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85% or at least 90% identical, preferably at least 95% or at least 97% or at least 99% identical to a FOXP3 polypeptide or a polynucleotide encoding a FOXP3 polypeptide, e.g., to SEQ ID NO. 423. FOXP3 variants may have the same or similar activity to a wildtype FOXP3 polypeptide or polynucleotide, e.g., may have at least 40, 50,60, 70, 80, 90, 95, 100, 110, 120, 130, 140 or 150% of the activity of a wildtype FOXP3 polypeptide orpolynucleotide. A person skilled in the art would be able to generate FOXP3 variants based on the known structural and functional features of FOXP3 and / or using conservative substitutions. FOXP3 variants may have similar or the same turnover time (or degradation rate) within a Treg cell as compared to wildtype FOXP3, e.g., at least 40, 50, 60, 70, 80, 90, 95, 99 or 100% of the turnover time (or degradation rate) ofwildtype FOXP3 in a Treg. Some FOXP3 variants may have a reduced turnover time (or degradation rate)as compared to wildtype FOXP3, for example, FOXP3 variants having amino acid substitutions at amino acid 418 and / or 422 of SEQ ID NO. 423, for example S418E and / or S422A, as described inWO2019 / 241549 (incorporated herein by reference) and are set out in SEQ ID NOs 425 to 427, whichrepresent the aa418, aa422 and aa418 and aa422 mutants respectively. Suitably, the FOXP3 polypeptide encoded by a nucleic acid molecule, construct or vector as described herein may comprise or consist of the polypeptide sequence of a human FOXP3, such as UniProtKB accession Q9BZS1 (SEQ ID NO: 423), or a functional fragment or variant thereof. In some embodiments of the invention, the FOXP3 polypeptide comprises or consists of an amino acidsequence which is at least 70% identical to SEQ ID NO: 423 or a functional fragment thereof. Suitably, theFOXP3 polypeptide comprises or consists of an amino acid sequence which is at least 80%, at least 85%,at least 90%, at least 95%, at least 98% or at least 99% identical to SEQ ID NO: 423 or a functional fragmentthereof. In some embodiments, the FOXP3 polypeptide comprises or consists of SEQ ID NO: 423 or afunctional fragment thereof. In some embodiments, as discussed above, the FOXP3 polypeptide may comprise mutations at residues 418 and / or 422 of SEQ ID NO.423, as set out in SEQ ID NO.425, SEQ ID NO.426, or SEQ ID NO.427. In some embodiments of the invention, the FOXP3 polypeptide may be truncated at the N and / or C terminalends, resulting in the production of a functional fragment. Particularly, an N and C terminally truncatedfunctional fragment of FOXP3 may comprise or consist of an amino acid sequence of SEQ ID NO. 424 ora functional variant thereof having at least 80, 85, 90, 95 or 99% identity thereto. Suitably, the FOXP3 polypeptide may be a variant of SEQ ID NO: 423, for example a natural variant.Suitably, the FOXP3 polypeptide is an isoform of SEQ ID NO: 423. For example, the FOXP3 polypeptidemay comprise a deletion of amino acid positions 72-106 relative to SEQ ID NO: 423. Alternatively, the FOXP3 polypeptide may comprise a deletion of amino acid positions 246-272 relative to SEQ ID NO: 423.Suitably, the FOXP3 polypeptide comprises SEQ ID NO: 428 or a functional fragment thereof. SEQ ID NO:428 represents an illustrative FOXP3 polypeptide.Suitably the FOXP3 polypeptide comprises or consists of an amino acid sequence which is at least 70%identical to SEQ ID NO: 428 or a functional fragment thereof. Suitably, the FOXP3 polypeptide comprisesan amino acid sequence which is at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or atleast 99% identical to SEQ ID NO: 428 or a functional fragment thereof. In some embodiments, the FOXP3polypeptide comprises or consists of SEQ ID NO: 428 or a functional fragment thereof.Suitably, the FOXP3 polypeptide may be a variant of SEQ ID NO: 428, for example a natural variant.Suitably, the FOXP3 polypeptide is an isoform of SEQ ID NO: 428 or a functional fragment thereof. Forexample, the FOXP3 polypeptide may comprise a deletion of amino acid positions 72-106 relative to SEQID NO: 428. Alternatively, the FOXP3 polypeptide may comprise a deletion of amino acid positions 246-272 relative to SEQ ID NO: 428.Suitably, the polynucleotide encoding a FOXP3 polypeptide comprises or consists of a nucleotide sequenceset forth in SEQ ID NO: 429, which represents an illustrative FOXP3 nucleotide sequence.In some embodiments of the invention, the polynucleotide encoding the FOXP3 polypeptide or variantcomprises nucleotide sequence which is at least 70% identical to SEQ ID NO: 429 or a fragment thereofwhich encodes a functional FOXP3 polypeptide. Suitably, the polynucleotide encoding the FOXP3 polypeptide or variant comprises a polynucleotide sequence which is at least 80%, at least 85%, at least90%, at least 95%, at least 98% or at least 99% identical to SEQ ID NO: 429 or a fragment thereof whichencodes a functional FOXP3 polypeptide. In some embodiments of the invention, the polynucleotideencoding the FOXP3 polypeptide or variant comprises or consists of SEQ ID NO: 429 or a fragment thereofwhich encodes a functional FOXP3 polypeptide. Suitably, the polynucleotide encoding a FOXP3 polypeptide comprises or consists of a polynucleotidesequence set forth in SEQ ID NO: 430, which represents another illustrative FOXP3 nucleotide.In some embodiments of the invention, the polynucleotide encoding the FOXP3 polypeptide or variantcomprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 430 or a fragment thereofwhich encodes a functional FOXP3 polypeptide. Suitably, the polynucleotide encoding the FOXP3 polypeptide or variant comprises a polynucleotide sequence which is at least 80%, at least 85%, at least90%, at least 95%, at least 98% or at least 99% identical to SEQ ID NO: 430 or a fragment thereof whichencodes a functional FOXP3 polypeptide. In some embodiments of the invention, the polynucleotideencoding the FOXP3 polypeptide or variant comprises or consists of SEQ ID NO: 430 or a fragment thereofwhich encodes a functional FOXP3 polypeptide. A skilled person will appreciate that FOXP3 expression within a Treg may be increased indirectly by introducing a polynucleotide into the cell which encodes a protein which increases transcription and / ortranslation of FOXP3 or which increases the half life (e.g. by at least 10, 20, 30, 40, 50, 60, 70, 80 or 90%)or function of FOXP3 (e.g. determined by suppressive ability of a transduced Treg, measured as previouslydiscussed). For example, it may be possible to introduce a polynucleotide into a Treg which increasestranscription of endogenous FOXP3 by interacting with the endogenous FOXP3 promoter or non-coding sequences (CNS, e.g. CNS1, 2 or 3) which are found upstream of the coding region. Suitably, the polynucleotide encoding the FOXP3 polypeptide or functional fragment or variant thereof may be codon optimised. Suitably, the polynucleotide encoding the FOXP3 polypeptide or functional fragment or variant thereof may be codon optimised for expression in a human cell. As mentioned above, the nucleic acid molecule may comprise nucleotide sequences encoding self- cleavage sequences. Particularly, the self-cleaving sequences are self-cleaving peptides. Such sequences auto-cleave during protein production. Self-cleaving peptides which may be used are 2A peptides or 2A- like peptides which are known and described in the art, for example in Donnelly et al., Journal of General Virology, 2001, 82, 1027-1041, herein incorporated by reference.2A and 2A-like peptides are believed to cause ribosome skipping and result in a form of cleavage in which a ribosome skips the formation of peptide bond between the end of a 2A peptide and the downstream amino acid sequence. The "cleavage" occurs between the Glycine and Proline residues at the C-terminus of the 2A peptide meaning the upstream cistron will have a few additional residues added to the end, while the downstream cistron will start with the Proline. The term “cleavage” as used herein thus includes the skipping of peptide bond formation. Suitable self-cleaving domains include P2A, T2A, E2A, and F2A sequences as shown in SEQ ID NO: 431- 436 respectively. The sequences may be modified to include the amino acids GSG at the N-terminus ofthe 2A peptides. Thus, also included as possible options are sequences corresponding to SEQ ID NOs.431 - 436, but with GSG at the N termini thereof. Such modified alternative 2A sequences are known andreported in the art. Alternative 2A-like sequences which may be used are shown in Donnelly et al (supra),for example a TaV sequence.The self-cleaving sequences included in the nucleic acid molecule may be the same or different. In anembodiment they are both 2A sequences, in particular P2A and / or T2A sequences. The self-cleaving sequence may include an additional cleavage site, which may be cleaved by commonenzymes present in the cell. This may assist in achieving complete removal of the 2A sequences aftertranslation. Such an additional cleavage site may for example comprise a Furin cleavage site RXXR (SEQ ID NO: 435), for example RRKR (SEQ ID NO: 436). In a representative embodiment, the nucleic acid molecule may comprise a nucleotide sequence encoding any CAR as described herein directed against ASGPR. In a representative embodiment, the nucleic acidmolecule may comprise a nucleotide sequence encoding a CAR directed against ASGPR having thesequence of any one of SEQ ID NOs. 298 to 363 or a variant thereof as described herein, and optionally anucleotide sequence encoding a safety switch and a nucleotide sequence encoding FOXP3.As is clear from the above description in addition to the specific polypeptide and nucleotide sequencesmentioned herein, also encompassed is the use of variants, or derivatives and fragments thereof. The term “derivative” or “variant” as used interchangeably herein, in relation to proteins or polypeptides of the present invention includes any substitution of, variation of, modification of, replacement of, deletion of and / or addition of one (or more) amino acid residues from or to the sequence providing that the resultant protein or polypeptide retains the desired function (for example, where the derivative or variant is an antigen binding domain, the desired function may be the ability of the antigen binding domain to bind its targetantigen (for example, a variant of an antigen binding domain which binds to ASGPR retains the ability tobind ASGPR), where the derivative or variant is a signalling domain, the desired function may be the abilityof that domain to signal (e.g. activate or inactivate a downstream molecule), where the derivative or variant is a transcription factor (e.g. FOXP3), the desired function may be the ability of the transcription factor to bind to target DNA and / or to induce transcription or where the derivative or variant is a safety switch polypeptide, the desired function may be the ability of that polypeptide to induce cell death e.g. upon bindingof a molecule thereto. Alternatively viewed, the variants or derivatives referred to herein are functionalvariants or derivatives. For example, variant or derivative may have at least at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% function compared to the corresponding, reference sequence. The variant or derivative may have a similar or the same level of function as compared to the corresponding reference sequence or may have an increased level of function (e.g. increased by at least 10%, at least 20%, at least 30%, at least 40% or at least 50%). Typically, amino acid substitutions may be made, for example from 1, 2 or 3 to 10 or 20 substitutionsprovided that the modified sequence retains the required activity or ability. Amino acid substitutions mayinclude the use of non-naturally occurring analogues. For example, the variant or derivative may have atleast 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%,or at least 90% activity or ability compared to the corresponding, reference sequence. The variant orderivative may have a similar or the same level of activity or ability as compared to the corresponding, reference sequence or may have an increased level of activity or ability (e.g., increased by at least 10%, at least 20%, at least 30%, at least 40% or at least 50%). Proteins or peptides may also have deletions, insertions or substitutions of amino acid residues which produce a silent change and result in a functionally equivalent protein. Deliberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and / orthe amphipathic nature of the residues as long as the endogenous function is retained. For example,negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophilicity values include asparagine, glutamine, serine, threonine and tyrosine. Conservative substitutions may be made, for example according to Table 1 below. Table 1The derivative may be a homologue. The term “homologue” as used herein means an entity having acertain homology with the wild type amino acid sequence and the wild type nucleotide sequence. The term “homology” can be equated with “identity”. A homologous or variant sequence may include an amino acid sequence which may be at least 70%, 75%, 85% or 90% identical, preferably at least 95%, 96%, 97%, 98% or 99% identical to the subject sequence. Typically, the variants will comprise the same active sites etc. as the subject amino acidsequence. Although homology can also be considered in terms of similarity (i.e., amino acid residueshaving similar chemical properties / functions), in the context herein it is preferred to express homology interms of sequence identity. Homology comparisons can be conducted by eye or, more usually, with the aid of readily available sequence comparison programs. These commercially available computer programs can calculate percentage homology or identity between two or more sequences. Percentage homology or sequence identity may be calculated over contiguous sequences, i.e., one sequence is aligned with the other sequence and each amino acid in one sequence is directly compared with the corresponding amino acid in the other sequence, one residue at a time. This is called an “ungapped” alignment. Typically, such ungapped alignments are performed only over a relatively short number of residues. Although this is a very simple and consistent method, it fails to take into consideration that, for example, in an otherwise identical pair of sequences, one insertion or deletion in the nucleotide sequence may cause the following codons to be put out of alignment, thus potentially resulting in a large reduction in percenthomology when a global alignment is performed. Consequently, most sequence comparison methods aredesigned to produce optimal alignments that take into consideration possible insertions and deletionswithout penalising unduly the overall homology score. This is achieved by inserting “gaps” in the sequencealignment to try to maximise local homology.However, these more complex methods assign “gap penalties” to each gap that occurs in the alignment sothat, for the same number of identical amino acids, a sequence alignment with as few gaps as possible, reflecting higher relatedness between the two compared sequences, will achieve a higher score than one with many gaps. “Affine gap costs” are typically used that charge a relatively high cost for the existence ofa gap and a smaller penalty for each subsequent residue in the gap. This is the most commonly used gapscoring system. High gap penalties will of course produce optimised alignments with fewer gaps. Mostalignment programs allow the gap penalties to be modified. However, it is preferred to use the defaultvalues when using such software for sequence comparisons. For example, when using the GCG WisconsinBestfit package the default gap penalty for amino acid sequences is -12 for a gap and -4 for each extension. Calculation of maximum percentage homology / sequence identity therefore firstly requires the production ofan optimal alignment, taking into consideration gap penalties. A suitable computer program for carryingout such an alignment is the GCG Wisconsin Bestfit package (University of Wisconsin, U.S.A.; Devereuxet al. (1984) Nucleic Acids Res. 12: 387). Examples of other software that can perform sequencecomparisons include, but are not limited to, the BLAST package (see Ausubel et al. (1999) ibid – Ch.18),FASTA (Atschul et al. (1990) J. Mol. Biol. 403-410) and the GENEWORKS suite of comparison tools. BothBLAST and FASTA are available for offline and online searching (see Ausubel et al. (1999) ibid, pages 7-58 to 7-60). However, for some applications, it is preferred to use the GCG Bestfit program. Another tool,called BLAST 2 Sequences is also available for comparing protein and nucleotide sequences (see FEMS Microbiol. Lett. (1999) 174: 247-50; FEMS Microbiol. Lett. (1999) 177: 187-8). Although the final percentage homology can be measured in terms of identity, the alignment process itselfis typically not based on an all-or-nothing pair comparison. Instead, a scaled similarity score matrix isgenerally used that assigns scores to each pairwise comparison based on chemical similarity orevolutionary distance. An example of such a matrix commonly used is the BLOSUM62 matrix – the defaultmatrix for the BLAST suite of programs. GCG Wisconsin programs generally use either the public defaultvalues or a custom symbol comparison table if supplied (see the user manual for further details). For someapplications, it is preferred to use the public default values for the GCG package, or in the case of othersoftware, the default matrix, such as BLOSUM62. Suitably, the percentage identity is determined acrossthe entirety of the reference and / or the query sequence. Once the software has produced an optimal alignment, it is possible to calculate percentage homology,preferably percentage sequence identity. The software typically does this as part of the sequencecomparison and generates a numerical result. “Fragment” typically refers to a selected region of the polypeptide or polynucleotide that is of interestfunctionally, e.g. is functional or encodes a functional fragment. “Fragment” thus refers to an amino acid ornucleic acid sequence that is a portion (or part) of a full-length polypeptide or polynucleotide.Such variants, derivatives and fragments may be prepared using standard recombinant DNA techniquessuch as site-directed mutagenesis. Where insertions are to be made, synthetic DNA encoding the insertiontogether with 5' and 3' flanking regions corresponding to the naturally-occurring sequence either side of theinsertion site may be made. The flanking regions will contain convenient restriction sites corresponding tosites in the naturally-occurring sequence so that the sequence may be cut with the appropriate enzyme(s)and the synthetic DNA ligated into the cut. The DNA is then expressed in accordance with the invention tomake the encoded protein. These methods are only illustrative of the numerous standard techniquesknown in the art for manipulation of DNA sequences and other known techniques may also be used. Nucleic acid molecules and polynucleotides / nucleotides / nucleic acid sequences as defined herein may comprise DNA or RNA. They may be single-stranded or double-stranded. It will be understood by a skilled person that numerous different nucleic acid molecules / polynucleotides can encode the same polypeptide as a result of the degeneracy of the genetic code. In addition, it is to be understood that the skilled person may, using routine techniques, make nucleotide substitutions that do not affect the polypeptide sequence encoded by the nucleic acid molecules / polynucleotides / nucleotide sequences as defined herein to reflect the codon usage of any particular host organism in which the polypeptides of the invention are to be expressed. The nucleic acid molecules / nucelootides / 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 nucleic acid molecules / polynucleotides as defined herein. Nucleic acid molecules / polynucleotides / nucleotide sequences such as DNA nucleic acid molecules / polynucleotides / sequences may be produced recombinantly, synthetically or by any means available to those of skill in the art. They may also be cloned by standard techniques. Longer nucleic acid molecules / polynucleotides / nucleotide sequences 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 human cell, performing a polymerase chain reaction under conditions which bring about amplification of 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 present nucleic acid molecules / nucleotides / polynucleotides may further comprise a nucleic acidsequence encoding a selectable marker. Suitably selectable markers are well known in the art and include,but are not limited to, fluorescent proteins – such as GFP. Suitably, the selectable marker may be afluorescent protein, for example GFP, YFP, RFP, tdTomato, dsRed, or variants thereof. In some embodiments the fluorescent protein is GFP or a GFP variant. The nucleic acid sequence encoding a selectable marker may be provided in combination with a nucleic acid molecule herein in the form of anucleic acid construct. Such a nucleic acid construct may be provided in a vector.Suitably, the selectable marker / reporter domain may be a luciferase-based reporter, a PET reporter (e.g.Sodium Iodide Symporter (NIS)), or a membrane protein (e.g. CD34, or Thy1.1). The nucleic acid sequences encoding one or more selectable markers may be separated from the present nucleic acid molecule, and / or from each other, by one or more co-expression sites which enablesexpression of each polypeptide as a discrete entity. Suitable co-expression sites are known in the art andinclude, for example, internal ribosome entry sites (IRES) and self-cleaving sites such as those included in the present nucleic acid molecules, and as defined above. In an embodiment this may be a 2A cleavage sites, as discussed above. The use of a selectable marker is advantageous as it allows cells (e.g., Tregs) in which a nucleic acid molecule, construct or vector of the present invention has been successfully introduced (such that theencoded ASGPR CAR and other modules, e.g., FOXP3 and safety switch polypeptide, are expressed) tobe selected and isolated from a starting cell population using common methods, e.g., flow cytometry. The nucleic acid molecules / nucleotides / polynucleotides used in the present invention may be codon- optimised. Codon optimisation has previously been described in WO1999 / 41397 andWO2001 / 79518. Different cells differ in their usage of particular codons. This codon bias corresponds toa bias in the relative abundance of particular tRNAs in the cell type. By altering the codons in the sequenceso that they are tailored to match with the relative abundance of corresponding tRNAs, it is possible toincrease expression. By the same token, it is possible to decrease expression by deliberately choosingcodons for which the corresponding tRNAs are known to be rare in the particular cell type. Thus, anadditional degree of translational control is available. The constructs of the present invention may comprise one or more regulatory sequences, for example apromoter. A “promoter” is a region of DNA that leads to initiation of transcription of a gene. Promoters arelocated near the transcription start sites of genes, upstream on the DNA (towards the 5’ region of the sensestrand). Any suitable promoter may be used, the selection of which may be readily made by the skilledperson. The promoter may be from any source, and may be a viral promoter, or a eukaryotic promoter,including mammalian or human promoters (i.e. a physiological promoter). In an embodiment the promoteris a viral promoter. Particular promoters include LTR promoters, EFS (or functional truncations thereof),SFFV, PGK, and CMV. In an embodiment the promoter is SFFV or a viral LTR promoter. Particularly, aSFFV promoter may be used within a nucleic acid molecule, construct or vector of the invention to allow initiation of transcription of the nucleotide sequence(s). The promoter may thus control the expression ofthe CAR of the invention. Where there is more than one nucleotide sequence, each sequence may beoperably linked to the same promoter, e.g. nucleotide sequences encoding the CAR, FOXP3 and / or the safety switch The SFFV promoter may comprise a nucleotide sequence as set out in SEQ ID NO.437. “Operably linked to the same promoter” means that transcription of the nucleic acid / nucleotide / polynucleotide sequences may be initiated from the same promoter (e.g., transcription of the first, second and third polynucleotide sequences is initiated from the same promoter) and that the nucleotide sequences are positioned and oriented for transcription to be initiated from thepromoter. Nucleic acids / nucleotides / polynucleotides operably linked to a promoter are undertranscriptional regulation of the promoter. In some embodiments of the invention, the nucleic acid / nucleotide / polynucleotide sequence is within an expression vector. The term “expression vector” as used herein means a construct enabling expression of the CAR polypeptide and any additional polypeptides such as a FOXP3 polypeptide or safety switch polypeptide. A vector is a tool that allows or facilitates the transfer of an entity from one environment to another. As used herein, and by way of example, some vectors used in recombinant nucleic acid techniques allow entities, such as a segment of nucleic acid (e.g., a heterologous DNA segment, such as a heterologous cDNA segment), to be transferred into a target cell. Vectors may be non-viral or viral. Examples of vectors used in recombinant nucleic acid techniques include, but are not limited to, plasmids, mRNA molecules (e.g., in vitro transcribed mRNAs), chromosomes, artificial chromosomes and viruses. The vector may also be, for example, a naked nucleic acid (e.g., DNA). In its simplest form, the vector may itself be a nucleotide of interest. The vectors used herein may be, for example, plasmid, mRNA or virus vectors and may include a promoter (as described above) for the expression of a nucleic acid molecule / polynucleotide and optionally a regulator of the promoter. In an embodiment the vector is a viral vector, for example a retroviral, e.g., a lentiviral vector or a gamma retroviral vector. The vectors may further comprise additional promoters, for example, in one embodiment, the promoter maybe a LTR, for example, a retroviral LTR or a lentiviral LTR. Long terminal repeats (LTRs) are identicalsequences of DNA that repeat hundreds or thousands of times found at either end of retrotransposons orproviral DNA formed by reverse transcription of retroviral RNA. They are used by viruses to insert theirgenetic material into the host genomes. Signals of gene expression are found in LTRs: enhancer, promoter(can have both transcriptional enhancers or regulatory elements), transcription initiation (such as capping), transcription terminator and polyadenylation signal. Suitably, the vector may include a 5’LTR and a 3’LTR.The vector may comprise one or more additional regulatory sequences which may act pre- or post-transcriptionally. “Regulatory sequences” are any sequences which facilitate expression of thepolypeptides, e.g., act to increase expression of a transcript or to enhance mRNA stability. Suitableregulatory sequences include for example enhancer elements, post-transcriptional regulatory elements andpolyadenylation sites. Suitably, the additional regulatory sequences may be present in the LTR(s).Suitably, the vector may comprise a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE), e.g., operably linked to the promoter. Vectors comprising the present nucleic acid molecules / polynucleotides may be introduced into cells using a variety of techniques known in the art, such as transformation and transduction. Several techniques are known in the art, for example infection with recombinant viral vectors, such as retroviral, lentiviral, adenoviral, adeno-associated viral, baculoviral and herpes simplex viral vectors; direct injection of nucleic acids and biolistic transformation. Non-viral delivery systems include but are not limited to DNA transfection methods. Here, transfectionincludes a process using a non-viral vector to deliver a gene to a target cell. Non-viral delivery systemscan include liposomal or amphipathic cell penetrating peptides, preferably complexed with a nucleic acid molecule or construct. Typical transfection methods include electroporation, DNA biolistics, lipid-mediated transfection, compacted DNA-mediated transfection, liposomes, immunoliposomes, lipofectin, cationic agent-mediated transfection, cationic facial amphiphiles (CFAs) (Nat. Biotechnol. (1996) 14: 556) and combinations thereof. Although the present nucleic acid molecules are designed to be used as single constructs, and this would be contained in a single vector, it is not precluded that they are introduced into a cell in conjunction with other vectors, for example encoding other polypeptides it may be desired also to introduce into the cell. Engineered cells may be generated by introducing a nucleic acid molecule, construct, or vector as defined herein, by one of many means including transduction with a viral vector, and transfection with DNA or RNA. The present cell may be made by: introducing to a cell (e.g. by transduction or transfection) the nucleic acid molecule / polynucleotide, construct or vector as defined herein. Suitable cells are discussed further below, but the cell may be from a sample isolated from a subject. The subject may be a donor subject, or a subject for therapy (i.e., the cell may be an autologous cell, or a donor cell, for introduction to another recipient, e.g., an allogeneic cell). The cell may be generated by a method comprising the following steps: (i) isolation of a cell-containing sample from a subject or provision of a cell-containing sample; and (ii) introduction into (e.g., by transduction or transfection) the cell-containing sample of a nucleic acid molecule, construct, or vector as defined herein, to provide a population of engineered cells. A target cell-enriched sample may be isolated from, enriched, and / or generated from the cell-containing sample prior to and / or after step (ii) of the method. For example, isolation, enrichment and / or generation of Tregs (or other target cells) may be performed prior to and / or after step (ii) to isolate, enrich or generate a Treg-enriched sample. Isolation and / or enrichment from a cell-containing sample may be performed afterstep (ii) to enrich for cells and / or Tregs (or other target cells) comprising the CAR, the nucleic acidmolecule / polynucleotide, the construct and / or the vector as described herein. A Treg-enriched sample may be isolated or enriched by any method known to those of skill in the art, for example by FACS and / or magnetic bead sorting. A Treg-enriched sample may be generated from the cell- containing sample by any method known to those of skill in the art, for example, from Tcon cells by introducing DNA or RNA coding for FOXP3 and / or from ex-vivo differentiation of inducible progenitor cells or embryonic progenitor cells. Methods for isolating and / or enriching other target cells are known in the art. Suitably, an engineered target cell may be generated by a method comprising the following steps: (i) isolation of a target-cell enriched sample from a subject or provision of a target cell-enriched sample; and (ii) introduction into (e.g., by transduction or transfection) the target cell-enriched sample of a nucleic acid, construct or vector as defined herein, to provide a population of engineered target cells. The target cell may be a Treg cell, or precursor or a progenitor thereof. An “engineered cell” means a cell which has been modified to comprise or express a polynucleotide whichis not naturally encoded by the cell. Methods for engineering cells are known in the art and include, but arenot limited to, genetic modification of cells e.g., by transduction such as retroviral or lentiviral transduction,transfection (such as transient transfection – DNA or RNA based) including lipofection, polyethylene glycol,calcium phosphate and electroporation, as discussed above. Any suitable method may be used to introduce a nucleic acid sequence into a cell. Non-viral technologies such as amphipathic cell penetrating peptidesmay be used to introduce nucleic acid. A cell may also be genetically modified e.g. using any known gene editing technique to insert a nucleotide, polynucleotide or nucleic acid sequence as described herein into the genome, e.g. using CRISPR, Talens or Zn fingers. Accordingly, the nucleic acid molecule as described herein is not naturally expressed by a corresponding, unmodified cell. Indeed, the nucleic acid molecule encoding the CAR is an artificial construct, and in an embodiment the safety switch polypeptide is an artificial construct, such they could not occur or be expressed naturally. Suitably, an engineered cell is a cell which has been modified e.g., by transduction orby transfection. Suitably, an engineered cell is a cell which has been modified or whose genome has beenmodified e.g., by transduction or by transfection. Suitably, an engineered cell is a cell which has been modified or whose genome has been modified by retroviral transduction. Suitably, an engineered cell is a cell which has been modified or whose genome has been modified by lentiviral transduction. As used herein, the term “introduced” refers to methods for inserting foreign nucleic acid, e.g., DNA or RNA, into a cell. As used herein the term introduced includes both transduction and transfection methods. Transfection is the process of introducing nucleic acids into a cell by non-viral methods. Transduction is theprocess of introducing foreign DNA or RNA into a cell via a viral vector. Engineered cells may be generatedby introducing a nucleic acid as described herein by one of many means including transduction with a viralvector, transfection with DNA or RNA. Cells may be activated and / or expanded prior to, or after, theintroduction of a nucleic acid as described herein, for example by treatment with an anti-CD3 monoclonal antibody or both anti-CD3 and anti-CD28 monoclonal antibodies. The cells may also be expanded in thepresence of anti-CD3 and anti-CD28 monoclonal antibodies in combination with IL-2. Suitably, IL-2 maybe substituted with IL-15. Other components which may be used in a cell (e.g., Treg) expansion protocolinclude, but are not limited to rapamycin, all-trans retinoic acid (ATRA) and TGFβ. As used herein“activated” means that a cell has been stimulated, causing the cell to proliferate. As used herein “expanded” means that a cell or population of cells has been induced to proliferate. The expansion of a population of cells may be measured for example by counting the number of cells present in a population. The phenotype of the cells may be determined by methods known in the art such as flow cytometry. The cell may be an immune cell, or a precursor therefor. A precursor cell may be a progenitor cell. Representative immune cells thus include T-cells, in particular, cytotoxic T-cells (CTLs; CD8+ T-cells), helper Tcells (HTLs; CD4+ T-cells) and regulatory T cells (Tregs). Other populations of T-cells are also useful herein, for example naive T-cells and memory T-cells. Other immune cells include NK cells, NKT cells, tolerogenic NK or NKT cells, dendritic cells, MDSC, neutrophils, and macrophages. Precursors of immune cells include pluripotent stem cells, e.g., induced PSC (iPSC), or more committed progenitors including multipotent stem cells (e.g. HPCs), or cells which are committed to a lineage. Precursor cells canbe induced to differentiate into immune cells in vivo or in vitro. In one aspect, a precursor cell may be asomatic cell which is capable of being transdifferentiated to an immune cell of interest. Most notably, the immune cell may be an NK cell, a dendritic cell, a MDSC, or a T cell, such as a cytotoxic T lymphocyte (CTL), helper T cell or a Treg cell. In a preferred embodiment the immune cell is a Treg cell. “Regulatory T cells (Treg) or T regulatory cells” are immune cells with immunosuppressive function that control cytopathic immune responses and areessential for the maintenance of immunological tolerance. As used herein, the term Treg refers to a T cellwith immunosuppressive function. A T cell as used herein is a lymphocyte including any type of T cell, such as an alpha beta T cell (e.g., CD8 or CD4+), a gamma delta T cell, a memory T cell, a Treg cell. Suitably, immunosuppressive function may refer to the ability of the Treg to reduce or inhibit one or more of a number of physiological and cellular effects facilitated by the immune system in response to a stimulus such as a pathogen, an alloantigen, or an autoantigen. Examples of such effects include increased proliferation of conventional T cell (Tconv) and secretion of proinflammatory cytokines. Any such effects may be used as indicators of the strength of an immune response. A relatively weaker immune responseby Tconv in the presence of Tregs would indicate an ability of the Treg to suppress immune responses. Forexample, a relative decrease in cytokine secretion would be indicative of a weaker immune response, andthus indicative of the ability of Tregs to suppress immune responses. Tregs can also suppress immuneresponses by modulating the expression of co-stimulatory molecules on antigen presenting cells (APCs), such as B cells, dendritic cells and macrophages. Expression levels of CD80 and CD86 can be used toassess suppression potency of activated Tregs in vitro after co-culture.Assays are known in the art for measuring indicators of immune response strength, and thereby the suppressive ability of Tregs. In particular, antigen-specific Tconv cells may be co-cultured with Tregs, and a peptide of the corresponding antigen added to the co-culture to stimulate a response from the Tconv cells. The degree of proliferation of the Tconv cells and / or the quantity of the cytokine IL-2 they secrete in response to addition of the peptide may be used as indicators of the suppressive abilities of the co-cultured Tregs. Antigen-specific Tconv cells co-cultured with Tregs as disclosed herein may proliferate 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 90%, 95% or 99% less than the same Tconv cells cultured in the absence ofthe Tregs. For example, antigen-specific Tconv cells co-cultured with the present Tregs may proliferate5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 90%, 95% or 99% less than the same Tconv cells cultured inthe presence of non-engineered Tregs. The cells comprising the nucleic acid, expression construct orvector as defined herein, e.g., Tregs, may have an increased suppressive activity as compared to non- engineered Tregs (e.g., an increased suppressive activity of at least 5, 10, 20, 30, 40, 50, 60, 70, 80 or 90%). Antigen-specific Tconv cells co-cultured with the Tregs herein may express at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, or at least 60% less effector cytokine than corresponding Tconv cells cultured in the absence of the Tregs (e.g., in the presence of non-engineered Tregs).The effector cytokine may be selected from IL-2, IL-17, TNFα, GM-CSF, IFN-γ, IL-4, IL-5, IL-9, IL-10 and IL-13. Suitably the effector cytokine may be selected from IL-2, IL-17, TNFα, GM-CSF and IFN-γ. Several different subpopulations of Tregs have been identified which may express different or differentlevels of particular markers. Tregs generally are T cells which express the markers CD4, CD25 and FOXP3(CD4+CD25+FOXP3+). Tregs may also express CTLA-4 (cytotoxic T-lymphocyte associated molecule-4) or GITR (glucocorticoid- induced TNF receptor). Treg cells are present in the peripheral blood, lymph nodes, and tissues and Tregs for use herein includethymus-derived, natural Treg (nTreg) cells, peripherally generated Tregs, and induced Treg (iTreg) cells.A Treg may be identified using the cell surface markers CD4 and CD25 in the absence of or in combinationwith low-level expression of the surface protein CD127 (CD4+CD25+CD127− or CD4+CD25+CD127low). Theuse of such markers to identify Tregs is known in the art and described in Liu et al. (JEM; 2006; 203; 7(10);1701-1711), for example. A Treg may be a CD4+CD25+FOXP3+T cell, a CD4+CD25+CD127−T cell, or a CD4+CD25+FOXP3+CD127− / lowT cell.Suitably, the Treg may be a natural Treg (nTreg). As used herein, the term “natural T reg” means a thymus-derived Treg. Natural Tregs are CD4+CD25+FOXP3+Helios+Neuropilin 1+. Compared with iTregs, nTregs have higher expression of PD-1 (programmed cell death-1, pdcd1), neuropilin 1 (Nrp1), Helios (Ikzf2), andCD73. nTregs may be distinguished from iTregs on the basis of the expression of Helios protein orNeuropilin 1 (Nrp1) individually. The Treg may have a demethylated Treg-specific demethylated region (TSDR). The TSDR is an important methylation-sensitive element regulating Foxp3 expression (Polansky, J.K., et al., 2008. European journal of immunology, 38(6), pp.1654-1663). Further suitable Tregs include, but are not limited to, Tr1 cells (which do not express Foxp3, and have high IL-10 production); CD8+FOXP3+T cells; and γδ FOXP3+T cells. Different subpopulations of Tregs are known to exist, including naïve Tregs (CD45RA+FoxP3low),effector / memory Tregs (CD45RA-FoxP3high) and cytokine-producing Tregs (CD45RA-FoxP3low). “MemoryTregs” are Tregs which express CD45RO and which are considered to be CD45RO+. These cells haveincreased levels of CD45RO as compared to naïve Tregs (e.g. at least 10, 20, 30, 40, 50, 60, 70, 80 or 90% more CD45RO) and which preferably do not express or have low levels of CD45RA (mRNA and / or protein) as compared to naïve Tregs (e.g. at least 80, 90 or 95% less CD45RA as compared to naïveTregs). “Cytokine-producing Tregs” are Tregs which do not express or have very low levels of CD45RA(mRNA and / or protein) as compared to naïve Tregs (e.g. at least 80, 90 or 95% less CD45RA as compared to naïve Tregs), and which have low levels of FOXP3 as compared to Memory Tregs, e.g. less than 50, 60,70, 80 or 90% of the FOXP3 as compared to Memory Tregs. Cytokine-producing Tregs may produceinterferon gamma and may be less suppressive in vitro as compared to naïve Tregs (e.g., less than 50, 60,70, 80 or 90% suppressive than naïve Tregs). Reference to expression levels herein may refer to mRNAor protein expression. Particularly, for cell surface markers such as CD45RA, CD25, CD4, CD45RO etc,expression may refer to cell surface expression, i.e., the amount or relative amount of a marker protein thatis expressed on the cell surface. Expression levels may be determined by any known method of the art. Forexample, mRNA expression levels may be determined by Northern blotting / array analysis, and proteinexpression may be determined by Western blotting, or preferably by FACS using antibody staining for cellsurface expression.Particularly, the Treg may be a naïve Treg. “A naïve regulatory T cell, a naïve T regulatory cell, or a naïveTreg” as used interchangeably herein refers to a Treg cell which expresses CD45RA (particularly whichexpresses CD45RA on the cell surface). Naïve Tregs are thus described as CD45RA+. Naïve Tregsgenerally represent Tregs which have not been activated through their endogenous TCRs by peptide / MHC, whereas effector / memory Tregs relate to Tregs which have been activated by stimulation through theirendogenous TCRs. Typically, a naïve Treg may express at least 10, 20, 30, 40, 50, 60, 70, 80 or 90% moreCD45RA than a Treg cell which is not naïve (e.g., a memory Treg cell). Alternatively viewed, a naïve Tregcell may express at least 2, 3, 4, 5, 10, 50 or 100-fold the amount of CD45RA as compared to a non-naïveTreg cell (e.g., a memory Treg cell). The level of expression of CD45RA can be readily determined bymethods of the art, e.g., by flow cytometry using commercially available antibodies. Typically, non-naïveTreg cells do not express CD45RA or low levels of CD45RA. Particularly, naïve Tregs may not express CD45RO, and may be considered to be CD45RO-. Thus, naïve Tregs may express at least 10, 20, 30, 40, 50, 60, 70, 80 or 90% less CD45RO as compared to a memory Treg, or alternatively viewed at least 2, 3, 4, 5, 10, 50 or 100 fold less CD45RO than a memory Treg cell. Although naïve Tregs express CD25 as discussed above, CD25 expression levels may be lower thanexpression levels in memory Tregs, depending on the origin of the naïve Tregs. For example, for naïveTregs isolated from peripheral blood, expression levels of CD25 may be at least 10, 20, 30, 40, 50, 60, 70,80 or 90% lower than memory Tregs. Such naïve Tregs may be considered to express intermediate to lowlevels of CD25. However, a skilled person will appreciate that naïve Tregs isolated from cord blood maynot show this difference. Typically, a naïve Treg as defined herein may be CD4+, CD25+, FOXP3+, CD127low, CD45RA+. Low expression of CD127 as used herein refers to a lower level of expression of CD127 as compared to aCD4+ non-regulatory or Tcon cell from the same subject or donor. Particularly, naïve Tregs may expressless than 90, 80, 70, 60, 50, 40, 30, 20 or 10% CD127 as compared to a CD4+non-regulatory or Tcon cellfrom the same subject or donor. Levels of CD127 can be assessed by methods standard in the art,including by flow cytometry of cells stained with an anti-CD127 antibody. Typically, naïve Tregs do not express, or express low levels of CCR4, HLA-DR, CXCR3 and / orCCR6. Particularly, naïve Tregs may express lower levels of CCR4, HLA-DR, CXCR3 and CCR6 thanmemory Tregs, e.g., at least 10, 20, 30, 40, 50, 60, 70, 80 or 90% lower level of expression. Naïve Tregs may further express additional markers, including CCR7+and CD31+.Isolated naïve Tregs may be identified by methods known in the art, including by determining the presenceor absence of a panel of any one or more of the markers discussed above, on the cell surface of the isolatedcells. For example, CD45RA, CD4, CD25 and CD127 low can be used to determine whether a cell is anaïve Treg. Methods of determining whether isolated cells are naïve Tregs or have a desired phenotypecan be carried out as discussed below in relation to additional steps which may be carried out, and methodsfor determining the presence and / or levels of expression of cell markers are well-known in the art andinclude, for example, flow cytometry, using commercially available antibodies. Suitably, the cell, such as a Treg, is isolated from peripheral blood mononuclear cells (PBMCs) obtainedfrom a subject. Suitably the subject from whom the PBMCs are obtained is a mammal, preferably ahuman. Suitably the cell is matched (e.g. HLA matched) or is autologous to the subject to whom theengineered cell is to be administered. Suitably, the subject to be treated is a mammal, preferably ahuman. The cell may be generated ex vivo either from a patient’s own peripheral blood (1st party), or inthe setting of a haematopoietic stem cell transplant from donor peripheral blood (2nd party), or peripheral blood from an unconnected donor (3rd party). Suitably the cell is autologous to the subject to whom the engineered cell is to be administered.Suitably, the Treg is part of a population of cells. Suitably, the population of Tregs comprises at least 70 %Tregs, such as at least 75, 85, 90, 95, 97, 98 or 99 % Tregs. Such a population may be referred to as an“enriched Treg population”.In some aspects, the Treg may be derived from ex-vivo differentiation of inducible progenitor cells (e.g.iPSCs) or embryonic progenitor cells to the Treg. A nucleic acid molecule or vector as described hereinmay be introduced into the inducible progenitor cells or embryonic progenitor cells prior to, or after,differentiation to a Treg. Suitable methods for differentiation are known in the art and include that disclosedin Haque et al, J Vis Exp., 2016, 117, 54720 (incorporated herein by reference). As used herein, the term “conventional T cell” or Tcon or Tconv (used interchangeably herein) means a T lymphocyte cell which expresses an αβ T cell receptor (TCR) as well as a co-receptor which may be cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) and which does not have an immunosuppressive function. Conventional T cells are present in the peripheral blood, lymph nodes, and tissues. Suitably, the engineered Treg may be generated from a Tcon by introducing the nucleic acid which includes a sequence coding for FOXP3. Alternatively, the engineered Treg may be generated from a Tconby in vitro culture of CD4+CD25-FOXP3- cells in the presence of IL-2 and TGF-β.In another embodiment the target cell into which the nucleic acid molecule, construct or vector is introduced is not a cell intended for therapy. In an embodiment the cell is a production host cell. The cell may be for production of the nucleic acid, e.g., cloning, or vector, or polypeptides. The invention also provides a cell population comprising a cell as defined or described herein. It will be appreciated that a cell population may comprise both cells of the invention comprising a nucleic acidmolecule, expression construct or vector as defined herein, and cells which do not comprise a nucleic acidmolecule, expression construct or vector of the invention, e.g., untransduced or untransfectedcells. Although in a preferred embodiment, all the cells in a population may comprise a nucleic acid,expression construct or vector of the invention, cell populations having at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 or 99% of cells comprising a nucleic acid, expression construct or vector of the invention areprovided. Further, the population of cells may comprise more than one cell type, although in a preferredembodiment, at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 or 99% of the cells are of the same type. Particularly, a cell population may comprise at least 70, 80, 90, 95 or 99% of T cells, more particularly Tregs. Additionally, at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 or 99% of the T cells, particularly Tregs, may comprise a nucleic acid, expression construct or vector of the invention. In particular, the invention provides a cell population comprising a plurality of cells comprising a CAR comprising an antigen recognition domain that specifically binds to ASGPR, or a nucleic acid molecule or vector encoding said CAR. There is also provided a pharmaceutical composition comprising a cell or cell population as defined or described herein, or a vector as defined herein. The vector may be used for gene therapy. Thus, rather than administering a cell, a vector may be administered instead, to modify endogenous cells in the subject to express the introduced nucleic acid molecule. Vectors suitable for use in gene therapy are known in the art, and include viral vectors.Thus, in a further aspect, the invention provides a cell, cell population or pharmaceutical composition asdefined herein for use in therapy. A pharmaceutical composition is a composition that comprises or consists of a therapeutically effective amount of a pharmaceutically active agent i.e., the cell (e.g., Treg), cell population or vector. It preferably includes a pharmaceutically acceptable carrier, diluent or excipient (including combinations thereof). Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit.1985). The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositionsmay comprise as - or in addition to - the carrier, excipient or diluent any suitable binder(s), lubricant(s),suspending agent(s), coating agent(s) or solubilising agent(s).By “pharmaceutically acceptable” it is included that the formulation is sterile and pyrogen free. The carrier,diluent, and / or excipient must be “acceptable” in the sense of being compatible with the cell or vector and not deleterious to the recipients thereof. Typically, the carriers, diluents, and excipients will be saline or infusion media which will be sterile and pyrogen free, however, other acceptable carriers, diluents, and excipients may be used. Examples of pharmaceutically acceptable carriers include, for example, water, salt solutions, alcohol, silicone, waxes, petroleum jelly, vegetable oils, polyethylene glycols, propylene glycol, liposomes, sugars, gelatin, lactose, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, perfume oil,fatty acid monoglycerides and diglycerides, petroethral fatty acid esters, hydroxymethyl-cellulose,polyvinylpyrrolidone, and the like. The cells, cell population or pharmaceutical compositions may be administered in a manner appropriate for treating and / or preventing the desired disease or condition. The quantity and frequency of administration will be determined by such factors as the condition of the subject, and the type and severity of the subject's disease or condition, although appropriate dosages may be determined by clinical trials. The pharmaceutical composition may be formulated accordingly. The cell, cell population or pharmaceutical composition as described herein can be administered parenterally, for example, intravenously or intrathecally, or they may be administered by infusion techniques. The cell, cell population or pharmaceutical composition may be administered in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solution may be suitably buffered (preferably to a pH of from 3 to 9). The pharmaceutical composition may be formulated accordingly. The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well-known to those skilled in the art. The pharmaceutical compositions may comprise cells in infusion media, for example sterile isotonicsolution. The pharmaceutical composition may be enclosed in ampoules, disposable syringes or multipledose vials made of glass or plastic. The cell, cell population or pharmaceutical composition may be administered in a single or in multipledoses. Particularly, the cell, cell population or pharmaceutical composition may be administered in a single,one-off dose. The pharmaceutical composition may be formulated accordingly. Depending upon the disease / condition and subject to be treated, as well as the route of administration, the cell, cell population or pharmaceutical composition may be administered at a specific stage of disease. The pharmaceutical composition may further comprise one or more active agents. The pharmaceutical composition may further comprise one or more other therapeutic agents, such as lympho-depletive agents (e.g. thymoglobulin, campath-1H, anti-CD2 antibodies, anti-CD3 antibodies, anti-CD20 antibodies, cyclophosphamide, fludarabine), inhibitors of mTOR (e.g. sirolimus, everolimus), drugs inhibitingcostimulatory pathways (e.g. anti-CD40 / CD40L, CTAL4Ig), and / or drugs inhibiting specific cytokines (IL-6,IL-17, TNFalpha, IL18). Depending upon the disease / condition and subject to be treated, as well as the route of administration, the cell, cell population or pharmaceutical composition may be administered at varying doses (e.g. measured in cells / kg or cells / subject). The physician in any event will determine the actual dosage which will be most suitable for any individual subject and it will vary with the age, weight and response of the particularsubject. Typically, however, for the cells herein, doses of 5x107 to 3x109 cells, or 108 to 2x109 cells persubject may be administered. The cell may be appropriately modified for use in a pharmaceutical composition. For example, cells may be cryopreserved and thawed at an appropriate time, before being infused into a subject. The invention further includes the use of kits comprising the cell, cell population and / or pharmaceuticalcomposition herein. Preferably said kits are for use in the methods and uses as described herein, e.g., thetherapeutic methods as described herein. Preferably said kits comprise instructions for use of the kit components. The cell, cell population and pharmaceutical composition of the invention may find particular utility in thetreatment of disorders associated with cells that express ASGPR, or with disorders where ASGPR islocalised at or near the site of disease, particularly disorders that would benefit from the immunosuppressive activity or target killing activity of the cells of the invention. The cells, cell populations, compositions and vectors herein may be for use in treating, preventing or reducing the risk of a disease or condition in a subject, notably a disease or condition which may be treated by or with the CAR. The cells and compositions containing them are for adoptive cell therapy (ACT). Various conditions may be treated by administration of cells, including particularly Treg cells, expressing a CARaccording to the present disclosure. As noted above, this may be conditions responsive toimmunosuppression, and particularly the immunosuppressive effects of Tregs cells. The cells, cell populations, compositions and vectors described herein may thus be used for inducing, or achieving, immunosuppression in a subject. The Treg cells administered, or modified in vivo, may be targeted by expression of the CAR. Conditions suitable for such treatment include autoimmune or inflammatory diseases, or more broadly a condition associated with any undesired or unwanted or deleterious immune response. Additionally, the cells, cell populations, compositions and vectors herein may be for use inpromoting tissue repair and / or tissue regeneration. Conditions to be treated or prevented includeinflammation, or alternatively put, a condition associated with or involving inflammation. Inflammation may be chronic or acute. Furthermore, the inflammation may be low-level or systemic inflammation.The term “target cell” refers to any cell expressing ASGPR to which the cell of the invention is to be directedto exert its therapeutic effect. In some embodiments, the target cell functions as a marker of a disease site, i.e. to attract the cells of the invention to provide an immunosuppressive effect. In some embodiments, the target cell is killed or abrogated by the cells of the invention. The engineered cells, e.g., Tregs, may be administered to a subject with a disease in order to lessen,reduce, or improve at least one symptom of disease. The at least one symptom may be lessened, reduced, or improved by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, or the at least one symptom may be completely alleviated.The engineered cells, e.g., Tregs may be administered to a subject with a disease in order to slow down,reduce, or block the progression of the disease. The progression of the disease may be slowed down, reduced, or blocked by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to a subject in which the engineered cells are not administered, or progression of the disease may be completely stopped. For example, the engineered Tregs may be administered to a subject with a liver disease (e.g. liver transplant rejection, liver GvHD, autoimmune liver disease, liver inflammation, liver failure) in order to lessen, reduce, or improve at least one symptom of liver disease such as jaundice, dark urine, itching,abdominal swelling or tenderness, fatigue, nausea or vomiting, and / or loss of appetite. The at least onesymptom may be lessened, reduced, or improved by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, or the at least one symptom may be completely alleviated. The engineered Tregs may be administered to a subject with a liver disease (e.g. liver transplant rejection, liver GvHD, autoimmune liver disease, liver inflammation, liver failure) in order to slow down, reduce, or block the progression of the liver disease. The progression of the disease may be slowed down, reduced, or blocked by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to a subject in which the engineered Tregs are not administered, or progression of the disease may be completely stopped. Alternatively, the engineered Tregs may be administered to a subject who has not yet contracted the disease and / or who is not showing any symptoms of the disease, to prevent the disease or to reduce or prevent development of at least one symptom associated with the disease. The subject may have a predisposition for, or be though to be at risk of developing, the disease. For example, the engineered Tregs may be administered to a subject who has not yet contracted and / or who is not showing any symptoms of liver disease (e.g. liver transplant rejection, liver GvHD, autoimmune liver disease, liver inflammation, liver failure) in order to reduce or prevent at least one symptom of liver disease such as jaundice, dark urine, itching, abdominal swelling or tenderness, fatigue, nausea or vomiting, and / or loss of appetite. The at least one symptom may be reduced by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to a subject in which the engineered Tregs are not administered, or the at least one symptom may be completely prevented. The engineered Tregs may be administered to a subject who has not yet contracted and / or who is not showing any symptoms of liver disease (e.g. liver transplant rejection, liver GvHD, autoimmune liver disease, liver inflammation, liver failure) in order to prevent the liver disease. The liver disease may beimpaired by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to a subjectin which the engineered Tregs are not administered, or the liver disease may be completely prevented. Liver disease includes conditions such as liver transplant rejection, liver GvHD, autoimmune liver disease, liver inflammation and liver failure, and particularly includes liver diseases associated with an undesired increased immune response in a subject which may result in liver damage or destruction. In a particular embodiment, liver disease may not, for example, include liver cancer, and more particularly may not includehepatocellular carcinoma (HCC). Liver disease thus preferably includes conditions which may be treatedor prevented by reduction of the immune response (e.g. by a reduction of at least 10, 20, 30, 40, 50, 60, 70, 80, or 90%), particularly in or near the liver. Liver transplant Liver transplantation is the only curative treatment option currently available for patients with end-stage liver disease. Despite recent advances in immunosuppressive agents, acute allograft rejection remains acommon complication of liver transplantation, with the incidence ranging from 20% to 40% of livertransplants. In most cases, rejection occurs within the first month following the liver transplant. Early rejection episodes do not significantly impair long term graft success or patient outcomes. In contrast, late- onset allograft rejection (>3-6 months following liver transplant) is associated with poor graft survival (Dogan, N., et al., 2018. Journal of International Medical Research, 46(9), pp.3979-3990). The present invention provides a method of inducing tolerance to a liver transplant, which comprises the step of administering an engineered Treg or a pharmaceutical composition of the invention to a subject. Suitably, the subject is mammal, preferably human. As used herein, “inducing tolerance to a liver transplant” refers to inducing tolerance to a transplanted liver in a recipient. In other words, inducing tolerance to a liver transplant means to reduce the level of a recipient’s immune response to a donor transplant organ. Inducing tolerance to a transplanted liver may decrease the incidence of rejection, reduce the amount of immunosuppressive drugs that the transplant patient requires, or may enable the discontinuation of immunosuppressive drugs. The present invention also provides a method of treating and / or preventing liver transplant rejection, which comprises the step of administering an engineered Treg or a pharmaceutical composition of the invention to a subject. Suitably, the subject is mammal, preferably human. Suitably, treating and / or preventing liver transplant rejection may refer to reducing the amount of immunosuppressive drugs that a liver transplant recipient requires, or may enable the discontinuation of immunosuppressive drugs.In one embodiment, the subject is a liver transplant recipient undergoing immunosuppression therapy. Inone embodiment, the present invention promotes liver tissue repair and / or liver regeneration preferably inaddition to inducing tolerance to a liver transplant or treating and / or preventing liver transplant rejection.Graft-versus-host disease The present invention provides a method of treating and / or preventing liver graft-versus-host disease (GvHD), which comprises the step of administering an engineered Treg or a pharmaceutical composition of the invention to a subject. The subject may be a liver transplant recipient. Suitably, the subject is mammal, preferably human. GvHD is a common complication following the receipt of transplanted tissue from a genetically different person. GvHD is commonly associated with stem cell transplants such as those that occur with bone marrow transplants. GvHD also applies to other forms of transplanted tissues such as liver transplants. White blood cells of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipient's body's cells, which leads to GvHD. In the classical sense, acute graft-versus- host-disease is characterized by selective damage to the liver, skin, mucosa, and the gastrointestinal tract. Accordingly, the subject may have liver damage, i.e. liver GvHD. In some embodiments the subject is a transplant recipient wherein the transplant is selected from liver, kidney, heart, lung, pancreas, intestine, stomach, bone marrow, vascularized composite tissue graft and skin transplant. Preferably the subject is a liver transplant recipient.In one embodiment, the subject is a liver transplant recipient undergoing immunosuppression therapy. Inone embodiment, the present invention promotes liver tissue repair and / or liver regeneration in addition to treating and / or preventing liver GvHD. Autoimmune liver disease The present invention provides a method of treating and / or preventing an autoimmune liver disease, which comprises the step of administering an engineered Treg or a pharmaceutical composition of the inventionto a subject. Suitably, the subject is mammal, preferably human.Suitably, the autoimmune liver disease is a chronic autoimmune liver disease. The autoimmune liverdisease may be selected from one or more of autoimmune hepatitis, primary biliary cholangitis and / or (primary) sclerosing cholangitis. Autoimmune liver diseases are chronic, slowly progressive, inflammatory liver diseases that may have overlapping features (Decock, S., McGee, P. and Hirschfield, G.M., 2009. Bmj, 339, p.b3305). Autoimmune hepatitis is usually a relapsing immune-mediated hepatitis. Patients present clinically with arthralgias and fatigue if symptomatic, and a third of patients present with cirrhosis. Raised liver enzymes (transaminases) characterise initial laboratory abnormalities. (Decock, S., McGee, P. and Hirschfield, G.M., 2009. Bmj, 339, p.b3305). Autoimmune hepatitis can also present as an acute disease that, if left untreated, leads to liver failure and death. Primary biliary cholangitis is a slowly progressive, chronic cholestatic disease and is characterised by small duct granulomatous cholangitis and biochemical cholestasis (raised alkaline phosphatase). Currently 60% of patients diagnosed with primary biliary cholangitis have no symptoms, and most have non-cirrhotic disease. When symptoms are present, fatigue, pruritus, and right upper quadrant discomfort are common, but do not indicate severity of disease. Even in the absence of symptoms, however, patients with primary biliary cholangitis have a significantly decreased long-term survival as compared to the general population (Decock, S., McGee, P. and Hirschfield, G.M., 2009. Bmj, 339, p.b3305). Primary sclerosing cholangitis is a chronic cholestatic liver disease characterised by fibrosing inflammatory destruction of the intrahepatic and / or extrahepatic biliary tree. There are currently no treatments for primary sclerosing cholangitis. Once symptoms are present, there is about a 50% chance of need for transplantation and 10% risk of cholangiocarcinoma over 10 years. (Decock, S., McGee, P. and Hirschfield, G.M., 2009. Bmj, 339, p.b3305). In one embodiment, the present invention promotes liver tissue repair and / or liver regeneration in addition to treating and / or preventing autoimmune liver disease. Liver inflammation The present invention provides a method of treating and / or preventing an inflammatory liver disorder, which comprises the step of administering an engineered Treg or a pharmaceutical composition of the invention to a subject. Suitably, the subject is mammal, preferably human. Inflammation of the liver tissue is also known as hepatitis. Hepatitis may be acute or chronic. Acute hepatitis can sometimes resolve on its own, progress to chronic hepatitis, or rarely result in acute liver failure. Over time the chronic form may progress to scarring of the liver (cirrhosis), chronic liver failure, and / or livercancer. Signs and symptoms of liver cirrhosis include jaundice, ascites (fluid accumulation in the abdominalcavity), fatigue and hepatic encephalopathy (brain dysfunction due to liver failure). Causes of hepatitis can be divided into the following major categories: infectious, metabolic, alcoholic, ischemic, autoimmune, genetic. Thus, in some embodiment the hepatitis is selected from infectious hepatitis, metabolic hepatitis, alcoholic hepatitis, ischemic hepatitis, autoimmune hepatitis, and genetic hepatitis. Infectious hepatitis includes viral hepatitis, parasitic hepatitis, and bacterial hepatitis. Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic viruses hepatitis A, B, C, D, and E. Other viruses can also cause liver inflammation,including cytomegalovirus, Epstein-Barr virus, and yellow fever. There also have been scores of recordedcases of viral hepatitis caused by herpes simplex virus. Parasitic hepatitis is liver inflammation due to a parasitic infection. Of the protozoans, Trypanosoma cruzi, Leishmania species, and the malaria-causing Plasmodium species all can cause liver inflammation. Of the worms, dog tapeworm, infects the liver and forms characteristic hepatic hydatid cysts. The liver flukes Fasciola hepatica and Clonorchis sinensis live in the bile ducts and cause progressive hepatitis and liver fibrosis. Bacterial hepatitis is liver inflammation due to a bacterial infection. Acute hepatitis is caused by Neisseria meningitidis, Neisseria gonorrhoeae, Bartonella henselae, Borrelia burgdorferi, salmonella species, brucella species and Campylobacter species. Chronic or granulomatous hepatitis is seen with infection from mycobacteria species, Tropheryma whipplei, Treponema pallidum, Coxiella burnetii, and rickettsia species. Alcoholic hepatitis is inflammation of the liver due to excessive intake of alcohol. Alcoholic hepatitis can have a chronic course that can lead to cirrhosis, liver failure and / or cancer, or an acute presentation. The severe cases of acute alcoholic hepatitis have a 50% 3 month mortality. Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can also cause toxic hepatitis. Non-alcoholic steatohepatitis, the most frequent form of metabolic hepatitis, is within the spectrum of non- alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease occurs in people with little or no history of alcohol use, and is instead strongly associated with metabolic syndrome, obesity, insulin resistance and diabetes, and hypertriglyceridemia. Non-alcoholic fatty liver disease can result in non-alcoholic steatohepatitis. Steatohepatitis is a type of fatty liver disease, characterized by inflammation ofthe liver with concurrent fat accumulation in liver, which can lead to cirrhosis, liver failure and / or liver cancer. Ischemic hepatitis also known as ischemic hepatopathy or shock liver, is a condition defined as an acute liver injury caused by insufficient blood flow (and consequently insufficient oxygen delivery) to the liver.Genetic causes of hepatitis include alpha- 1 -antitrypsin deficiency, hemochromatosis, and Wilson'sdisease. In some embodiments the liver inflammation has no identifiable cause.In one embodiment, the present invention promotes liver tissue repair and / or liver regeneration in additionto treating and / or preventing an inflammatory liver disorder. Liver repair or regeneration The present invention provides a method of promoting liver tissue repair and / or liver regeneration, which comprises the step of administering an engineered Treg or a pharmaceutical composition of the invention to a subject. Suitably, the subject is mammal, preferably human. The subject may have liver cirrhosis, acuteliver failure or acute-on- chronic liver failure.As used herein, “liver regeneration” may refer to the recreation of liver architecture and function following damage (e.g. acute damage), without leaving a scar (Cordero-Espinoza, L. and Huch, M., 2018. The Journal of clinical investigation, 128(1), pp.85-96). For example, liver regeneration may result in restoration of at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% of the original liver mass. The method of the present invention may reduce the time until maximal liver mass is achieved, for example the time may be reduced by at least 10%, at least 20%, at least 30%, at least 40%, or by at least 50% compared to a subject in which the engineered Treg or pharmaceutical composition are not administered. As used herein, “liver tissue repair” may refer to the recreation of liver architecture and function followingdamage (e.g. chronic damage), with scarring (i.e. fibrosis) (Cordero- Espinoza, L. and Huch, M., 2018. TheJournal of clinical investigation, 128(1), pp.85-96). This may be characterised by replacement of functional tissue parenchyma with a meshwork of extracellular matrix (ECM). The liver architecture may be altered and optimal function may be hindered. For example, liver repair may result in restoration of at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% of the original liver function. The method of the present invention may reduce the time until maximal liver function is reached, for example the time may bereduced by at least 10%, at least 20%, at least 30%, at least 40%, or by at least 50% compared to a subjectin which the engineered Treg or pharmaceutical composition are not administered. The engineered Treg of the invention may express genes involved in liver regeneration and tissue repair, thus promoting robust liver repair and / or regeneration. Although adult hepatocytes are long lived and normally do not undergo cell division, they maintain the ability to proliferate in response to inflammatory damage or following partial hepatectomy. This ability is most clearly shown by the two-thirds partial-hepatectomy model in rodents. In this model, two thirds of the liver is surgically removed, and the remaining liver enlarges until the original liver mass is restored -approximately 1 week after surgery - after which the regenerative process stops. In humans, liverregeneration occurs most frequently after liver damage by ischaemia or hepatitis. (Taub, R., 2004. Nature reviews Molecular cell biology, 5(10), p.836-847). A very similar phenomenon occurs in humans who undergo a partial hepatectomy as treatment for liver tumours or during living donor liver transplantation. In addition, in humans liver regeneration occurs following damage to the hepatocytes due to ischemia, toxics, and acute or chronic hepatitis. Suitably, the liver may be injured and / or damaged by hepatitis. In some embodiments, in addition to promoting liver tissue repair and / or liver regeneration, the engineered Treg of the invention further treats the hepatitis. The hepatitis may be selected from infectious hepatitis, metabolic hepatitis, alcoholic hepatitis, ischemic hepatitis, autoimmune hepatitis, and genetic hepatitis. In one embodiment, hepatitis may not be fulminant or chronic hepatitis. Due to liver regeneration, it has become possible to use partial livers from living donors for transplantation, thereby increasing the number of organs that are available for transplantation. Increasing numbers of liver transplants are being undertaken using living, related-donor tissue and small-for-size transplant organs, for which successful transplantation requires at least some liver regeneration and repair. (Taub, R., 2004. Nature reviews Molecular cell biology, 5(10), p.836-847). Thus, the subject may be a liver transplant recipient or a patient who is undergoing a partial hepatectomy (e.g. as a living donor for liver transplantation or due to the presence of a liver tumour that requires surgical resection). The liver may be a transplanted liver. Humans with certain hepatic conditions, including cirrhosis (fibrosis of the liver), steatosis (fatty liver), andeven those conditions that are due to old age, have impaired liver regeneration that results in increased morbidity and mortality in response to liver injury or damage. (Taub, R., 2004. Nature reviews Molecular cell biology, 5(10), p.836-847). Thus, the subject may have impaired liver regeneration, preferably due to one or more of acute liver failure, cirrhosis, acute-on-chronic liver failure, hepatitis, steatosis, steatohepatitis and old age. In one embodiment, the present invention treats and / or prevents immune-mediated damage in addition to promoting liver tissue repair and / or liver regeneration. For example, the present invention may also induce tolerance to a liver transplant in the subject, or treat and / or prevent liver transplant rejection, liver graft- versus-host disease (GvHD), an autoimmune liver disease, or an inflammatory liver disorder in the subject. Liver fibrosis, cirrhosis, acute liver failure and acute-on-chronic liver failure The present invention provides a method of treating and / or preventing liver fibrosis, liver cirrhosis, acute liver failure or acute-on-chronic liver failure. Improvement of liver fibrosis, liver cirrhosis, acute liver failure or acute-on-chronic liver failure will typically require treating and / or preventing immune-mediated damage of the liver and promoting liver regeneration. Liver fibrosis is one of the leading causes of mortality because it changes the architecture of certain organs and disrupts normal function. Liver fibrosis is a histological consequence of the wound-healing process resulting from chronic liver diseases such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and other liver disorders. Deposition of excess extracellular matrix (ECM) that is rich in fibril-forming collagens is a typical finding of liver fibrosis. The excess deposition of the ECM changes the normalarchitecture of the liver resulting in pathophysiologic damage to the organ (Suk, K.T. and Kim, D.J., 2015. World journal of hepatology, 7(3), p.607). Liver cirrhosis is defined as an advanced stage of liver fibrosis with distortion of the hepatic vasculature and architecture. Histologically, regenerative nodules with fibrous tissues form in response to chronic injury and lead to liver cirrhosis. Consequently, disruption of the liver architecture due to liver fibrosis and / or cirrhosis causes hemodynamic instability and portal hypertension (Suk, K.T. and Kim, D.J., 2015. World journal of hepatology, 7(3), p.607). Acute liver failure is defined herein as the rapid development of hepatocellular dysfunction, specifically coagulopathy and encephalopathy in a patient without known prior liver disease. For example, “acute hepatic failure" may be defined as the development of encephalopathy within 26 weeks of the onset of any hepatic symptoms. This may be sub-divided into "fulminant hepatic failure", which requires onset of encephalopathy within 8 weeks, and "subfulminant", which describes onset of encephalopathy after 8 weeks but before 26 weeks. Another scheme defines "hyperacute" as onset within 7 days, "acute" as onset between 7 and 28 days, and "subacute" as onset between 28 days and 24 weeks. Acute-on-chronic liver failure is characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases (Hernaez, R., et al., 2017. Gut, 66(3), pp.541-553). Suitably, the subject is a mammal. Suitably, the subject is a human. Suitably, the cell may be an engineered Treg cell and the cell population may be a population of engineeredTreg cells, which have been engineered to express a CAR as described herein. Suitably, the CAR maycomprise an antigen binding domain which is capable of specifically binding to ASGPR, i.e., the antigen is ASGPR. A method for treating a disease or condition relates to the therapeutic use of the cells herein. Suitably, treating and / or preventing an autoimmune or inflammatory disease may refer to administering an effective amount of the cells (e.g., Tregs) such that the amount of existing medication that a subject with said disease requires is reduced, or may enable the discontinuation of the subject’s existing medication.Preventing a disease or condition relates to the prophylactic use of the cells herein. In this respect, thecells may be administered to a subject who has not yet contracted or developed the disease or condition and / or who is not showing any symptoms of the disease or condition to prevent the disease or condition orto reduce or prevent development of at least one symptom associated with the disease or condition. Thesubject may have a predisposition for, or be thought to be at risk of developing, the disease or condition. As used herein, the term “treatment” refers to clinical intervention designed to alter the natural course of the individual being treated during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of progression, ameliorating or palliating the pathological state, and remission or improved prognosis of a particular disease, disorder, or condition. An individual is successfully “treated”, for example, if one or more symptoms associated with a particular disease, disorder, or condition are mitigated or eliminated.An “effective amount” refers to at least an amount effective, at dosages and for periods of time necessary,to achieve the desired therapeutic or prophylactic result. An effective amount can be provided in one or more administrations.A “therapeutically effective amount” is at least the minimum concentration required to affect a measurableimprovement of a particular disease, disorder, or condition. A therapeutically effective amount herein may vary according to factors such as the disease state, age, sex, and weight of the patient, and the ability of the chimeric receptors to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the cell, cell population or pharmaceutic compositions are outweighed by the therapeutically beneficial effects.The terms “subject”, “patient” and “individual” are used interchangeably herein and refer to a mammal,preferably a human. In particular, the terms subject, patient and individual refer to a human having a disease or disorder as defined herein in need of treatment. In some embodiments of the invention, the patient may be subjected to other treatments prior to,contemporaneously with, or after the treatments of the present invention. For instance, in someembodiments, the patient may be treated with other procedures for the treatment of symptoms associated with the disease or disorder. The medical use of or method herein may involve the steps of: (i) isolating a cell-containing sample or providing a cell-containing sample; (ii) introducing a nucleic acid molecule, construct or a vector as defined herein to the cell; and (iii) administering the cells from (ii) to a subject. The cell may be a Treg as defined herein. An enriched Treg population may be isolated and / or generated from the cell containing sample prior to, and / or after, step (ii) of the method. For example, isolation and / or generation may be performed prior to and / or after step (ii) to isolate and / or generate an enriched Treg sample. Enrichment may be performed after step (ii) to enrich for cells and / or Tregs comprising the CAR, the polynucleotide, and / or the vector as described herein. Suitably, the cell may be autologous. Suitably, the cell may be allogenic. Suitably, the cell (e.g., the engineered Treg) may be administered in combination with one or more other therapeutic agents, such as lympho-depletive agents (e.g., as discussed above). The engineered cell, e.g., Treg, may be administered simultaneously with or sequentially with (i.e., prior to or after) the one or more other therapeutic agents. Cells, e.g., Tregs, may be activated and / or expanded prior to, or after, the introduction of a nucleic acid molecule as described herein, for example by treatment with an anti-CD3 monoclonal antibody or both anti-CD3 and anti-CD28 monoclonal antibodies. Expansion protocols are discussed above.The cell, e.g., Tregs, may be washed after each step of the method, in particular after expansion.The population of engineered cells, e.g., Treg cells may be further enriched by any method known to thoseof skill in the art, for example by FACS or magnetic bead sorting. The steps of the method of production may be performed in a closed and sterile cell culture system. The invention may also provide a method for increasing the stability and / or suppressive function of a cell comprising the step of introducing a nucleic acid molecule, an expression construct or vector as providedherein into the cell. An increase in suppressive function can be measured as discussed above, for exampleby co-culturing activated antigen-specific Tconv cells with cells of the invention, and for example measuringthe levels the cytokines produced by the Tconv cells. An increase in suppressive function may be anincrease of at least 10, 20, 30, 40, 50, 60, 70, 80, or 90% as compared to a non-engineered Treg. An increase in stability of a cell, e.g., a Treg as defined herein, refers to an increase in the persistence or survival of those cells or to an increase in the proportion of cells retaining a Treg phenotype over a time period (e.g., to cells retaining Treg markers such as FOXP3 and Helios) as compared to a non-engineered Treg. An increase in stability may be an increase in stability of at least 10, 20, 30, 40, 50, 60, 70, 80 or 90%, and may be measured by techniques known in the art, e.g., staining of Treg cell markers within a population of cells, and analysis by FACS. This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methodsand materials similar or equivalent to those described herein can be used in the practice or testing ofembodiments of this disclosure. Numeric ranges are inclusive of the numbers defining the range. Unlessotherwise indicated, any nucleic acid sequences are written left to right in 5’ to 3’ orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of thatrange is also specifically disclosed. Each smaller range between any stated value or intervening value ina stated range and any other stated or intervening value in that stated range is encompassed within thisdisclosure. The upper and lower limits of these smaller ranges may independently be included or excludedin the range, and each range where either, neither or both limits are included in the smaller ranges is alsoencompassed within this disclosure, subject to any specifically excluded limit in the stated range. Wherethe stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in this disclosure. 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” or “containing”, “contains”, and are inclusive or open-ended and do not exclude additional, non- recited members, elements or method steps. The terms “comprising”, “comprises” and “comprised of’ also include the term “consisting of’.The publications discussed herein are provided solely for their disclosure prior to the filing date of thepresent application. Nothing herein is to be construed as an admission that such publications constituteprior art to the claims appended hereto.The following numbered paragraphs define particular embodiments of the present invention:1. A chimeric antigen receptor (CAR) comprising an antigen recognition domain that specificallybinds to ASGPR, wherein the antigen recognition domain comprises a VH CDR3 having a sequence selected from SEQ ID NOs: 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, 117, 123, 129, 135, 141, 147, 153, 159, 165, 171, 177, 183, 189 and 195 or a sequence comprising from 1 to 3 amino acid modifications relative to one of SEQ ID NOs: 33, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, 117, 123, 129, 135, 141, 147, 153, 159, 165, 171, 177, 183, 189 and 195. 2. The CAR of paragraph 1, wherein the antigen recognition domain comprises VH CDR1, 2 and 3sequences set forth in: (i) SEQ ID NOs: 1, 2 and 3 respectively;(ii) SEQ ID NOs: 7, 8 and 9 respectively;(iii) SEQ ID NOs: 13, 14 and 15 respectively;(iv) SEQ ID NOs: 19, 20 and 21 respectively;(v) SEQ ID NOs: 25, 26 and 27 respectively;(vi) SEQ ID NOs: 31, 32 and 33 respectively;(vii) SEQ ID NOs: 37, 38 and 39 respectively;(viii) SEQ ID NOs: 43, 44 and 45 respectively;(ix) SEQ ID NOs: 49, 50 and 51 respectively;(x) SEQ ID NOs: 55, 56 and 57 respectively;(xi) SEQ ID NOs: 61, 62 and 63 respectively;(xii) SEQ ID NOs: 67, 68 and 69 respectively;(xiii) SEQ ID NOs: 73, 74 and 75 respectively;(xiv) SEQ ID NOs: 79, 80 and 81 respectively;(xv) SEQ ID NOs: 85, 86 and 87 respectively;(xvi) SEQ ID NOs: 91, 92 and 93 respectively;(xvii) SEQ ID NOs: 97, 98 and 99 respectively;(xviii) SEQ ID NOs: 103, 104 and 105 respectively;(xix) SEQ ID NOs: 109, 110 and 111 respectively;(xx) SEQ ID NOs: 115, 116 and 117 respectively;(xxi) SEQ ID NOs: 121, 122 and 123 respectively;(xxii) SEQ ID NOs: 127, 128 and 129 respectively;(xxiii) SEQ ID NOs: 133, 134 and 135 respectively;(xxiv) SEQ ID NOs: 139, 140 and 141 respectively;(xxv) SEQ ID NOs: 145, 146 and 147 respectively;(xxvi) SEQ ID NOs: 151, 152 and 153 respectively;(xxvii) SEQ ID NOs: 157, 158 and 159 respectively;(xxviii) SEQ ID NOs: 163, 164 and 165 respectively;(xxix) SEQ ID NOs: 169, 170 and 171 respectively;(xxx) SEQ ID NOs: 175, 176 and 177 respectively;(xxxi) SEQ ID NOs: 181, 182 and 183 respectively;(xxxii) SEQ ID NOs: 187, 188 and 189 respectively; or(xxxiii) SEQ ID NOs: 193, 194 and 195 respectively;wherein one or more of said VH CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 amino acid modifications relative to an aforementioned CDR sequence.The CAR of paragraph 1 or 2, wherein the antigen recognition domain comprises a VL CDR3having a sequence selected from SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192 and 198 or a sequence comprising from 1 to 3 amino acid modifications relative to one of SEQ IDNOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132,138, 144, 150, 156, 162, 168, 174, 180, 186, 192 and 198.The CAR of any preceding paragraph, wherein the antigen recognition domain comprises VLCDR1, 2 and 3 sequences set forth in: (i) SEQ ID NOs: 4, 5 and 6 respectively;(ii) SEQ ID NOs: 10, 11 and 12 respectively;(iii) SEQ ID NOs: 16, 17 and 18 respectively;(iv) SEQ ID NOs: 22, 23 and 24 respectively;(v) SEQ ID NOs: 28, 29 and 30 respectively;(vi) SEQ ID NOs: 34, 35 and 36 respectively;(vii) SEQ ID NOs: 40, 41 and 42 respectively;(viii) SEQ ID NOs: 46, 47 and 48 respectively;(ix) SEQ ID NOs: 52, 53 and 54 respectively;(x) SEQ ID NOs: 58, 59 and 60 respectively;(xi) SEQ ID NOs: 64, 65 and 66 respectively;(xii) SEQ ID NOs: 70, 71 and 72 respectively;(xiii) SEQ ID NOs: 76, 77 and 78 respectively;(xiv) SEQ ID NOs: 82, 83 and 84 respectively;(xv) SEQ ID NOs: 88, 89 and 90 respectively;(xvi) SEQ ID NOs: 94, 95 and 96 respectively;(xvii) SEQ ID NOs: 100, 101 and 102 respectively;(xviii) SEQ ID NOs: 106, 107 and 108 respectively;(xix) SEQ ID NOs: 112, 113 and 114 respectively;(xx) SEQ ID NOs: 118, 119 and 120 respectively;(xxi) SEQ ID NOs: 124, 125 and 126 respectively;(xxii) SEQ ID NOs: 130, 131 and 132 respectively;(xxiii) SEQ ID NOs: 136, 137 and 138 respectively;(xxiv) SEQ ID NOs: 142, 143 and 144 respectively;(xxv) SEQ ID NOs: 148, 149 and 150 respectively;(xxvi) SEQ ID NOs: 154, 155 and 156 respectively;(xxvii) SEQ ID NOs: 160, 161 and 162 respectively;(xxviii) SEQ ID NOs: 166, 167 and 168 respectively;(xxix) SEQ ID NOs: 172, 173 and 174 respectively;(xxx) SEQ ID NOs: 178, 179 and 180 respectively;(xxxi) SEQ ID NOs: 184, 185 and 186 respectively;(xxxii) SEQ ID NOs: 190, 191 and 192 respectively; or(xxxiii) SEQ ID NOs: 196, 197 and 198 respectively;wherein one or more of said VL CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 amino acid modifications relative to an aforementioned CDR sequence.The CAR of any preceding paragraph, wherein the antigen recognition domain is a single chainantibody (scFv).The CAR of any preceding paragraph, wherein the antigen recognition domain comprises:(i) VH CDR 1, 2 and 3 sequences set forth in SEQ ID NOs: 1, 2 and 3 respectivelyand VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 4, 5 and 6 respectively; (ii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 7, 8 and 9 respectivelyand VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 10, 11 and 12 respectively; (iii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 13, 14 and 15respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 16, 17 and 18 respectively; (iv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 19, 20 and 21respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 22, 23 and 24 respectively;(v) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 25, 26 and 27respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 28, 29 and 30 respectively;(vi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 31, 32 and 33respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 34, 35 and 36 respectively;(vii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 37, 38 and 39respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 40, 41and 42 respectively;(viii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 43, 44 and 45respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 46, 47 and 48 respectively;(ix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 49, 50 and 51respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 52, 53 and 54 respectively;(x) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 55, 56 and 57respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 58, 59 and 60 respectively;(xi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 61, 62 and 63respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 64, 65 and 66 respectively;(xii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 67, 68 and 69respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 70, 71 and 72 respectively;(xiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 73, 74 and 75respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 76, 77 and 78 respectively;(xiv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 79, 80 and 81respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 82, 83 and 84 respectively;(xv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 85, 86 and 87respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 88, 89 and 90 respectively;(xvi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 91, 92 and 93respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 94, 95 and 96 respectively;(xvii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 97, 98 and 99respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 100, 101 and 102 respectively;(xviii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 103, 104 and 105respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 106,107 and 108 respectively;(xix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 109, 110 and 111respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 112, 113 and 114 respectively;(xx) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 115, 116 and 117respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 118, 119 and 120 respectively;(xxi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 121, 122 and 123respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 124, 125 and 126 respectively;(xxii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 127, 128 and 129respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 130, 131 and 132 respectively;(xxiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 133, 134 and 135respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 136, 137 and 138 respectively;(xxiv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 139, 140 and 141respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 142, 143 and 144 respectively;(xxv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 145, 146 and 147respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 148, 149 and 150 respectively;(xxvi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 151, 152 and 153respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 154, 155 and 156 respectively;(xxvii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 157, 158 and 159respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 160, 161 and 162 respectively;(xxviii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 163, 164 and 165respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 166, 167 and 168 respectively;(xxix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 169, 170 and 171respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 172, 173 and 174 respectively;(xxx) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 175, 176 and 177respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 178, 179 and 180 respectively;(xxxi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 181, 182 and 183respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 184, 185 and 186 respectively;(xxxii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 187, 188 and 189respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 190, 191 and 192 respectively; or(xxxiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 193, 194 and 195respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 196, 197 and 198 respectively; wherein one or more of said CDR sequences of (i) to (xxxiii) optionally comprises from 1no acid modifications relative to an aforementioned CDR sequence. of any preceding paragraph, wherein the antigen recognition domain comprises:(i) a VH domain comprising the sequence set forth in SEQ ID NO: 199, or asequence having at least 70% identity thereto, and a VL domain comprising ...

Claims

CLAIMS1. A chimeric antigen receptor (CAR) comprising an antigen recognition domain that specificallybinds to ASGPR, wherein the antigen recognition domain comprises a VH CDR3 having a sequence selected from SEQ ID NOs: 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, 117, 123, 129, 135, 141, 147, 153, 159, 165, 171, 177, 183, 189 and 195 or a sequence comprising from 1 to 3 amino acid modifications relative to one of SEQ ID NOs: 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, 117, 123, 129, 135, 141, 147, 153, 159, 165, 171, 177, 183, 189 and 195.

2. The CAR of claim 1, wherein the antigen recognition domain comprises VH CDR1, 2 and 3sequences set forth in: (i) SEQ ID NOs: 1, 2 and 3 respectively;(ii) SEQ ID NOs: 7, 8 and 9 respectively;(iii) SEQ ID NOs: 13, 14 and 15 respectively;(iv) SEQ ID NOs: 19, 20 and 21 respectively;(v) SEQ ID NOs: 25, 26 and 27 respectively;(vi) SEQ ID NOs: 31, 32 and 33 respectively;(vii) SEQ ID NOs: 37, 38 and 39 respectively;(viii) SEQ ID NOs: 43, 44 and 45 respectively;(ix) SEQ ID NOs: 49, 50 and 51 respectively;(x) SEQ ID NOs: 55, 56 and 57 respectively;(xi) SEQ ID NOs: 61, 62 and 63 respectively;(xii) SEQ ID NOs: 67, 68 and 69 respectively;(xiii) SEQ ID NOs: 73, 74 and 75 respectively;(xiv) SEQ ID NOs: 79, 80 and 81 respectively;(xv) SEQ ID NOs: 85, 86 and 87 respectively;(xvi) SEQ ID NOs: 91, 92 and 93 respectively;(xvii) SEQ ID NOs: 97, 98 and 99 respectively;(xviii) SEQ ID NOs: 103, 104 and 105 respectively;(xix) SEQ ID NOs: 109, 110 and 111 respectively;(xx) SEQ ID NOs: 115, 116 and 117 respectively;(xxi) SEQ ID NOs: 121, 122 and 123 respectively;(xxii) SEQ ID NOs: 127, 128 and 129 respectively;(xxiii) SEQ ID NOs: 133, 134 and 135 respectively;(xxiv) SEQ ID NOs: 139, 140 and 141 respectively;(xxv) SEQ ID NOs: 145, 146 and 147 respectively;(xxvi) SEQ ID NOs: 151, 152 and 153 respectively;(xxvii) SEQ ID NOs: 157, 158 and 159 respectively;(xxviii) SEQ ID NOs: 163, 164 and 165 respectively;(xxix) SEQ ID NOs: 169, 170 and 171 respectively;(xxx) SEQ ID NOs: 175, 176 and 177 respectively;(xxxi) SEQ ID NOs: 181, 182 and 183 respectively;(xxxii) SEQ ID NOs: 187, 188 and 189 respectively; or(xxxiii) SEQ ID NOs: 193, 194 and 195 respectively;wherein one or more of said VH CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 amino acid modifications relative to an aforementioned CDR sequence.

3. The CAR of claim 1 or 2, wherein the antigen recognition domain comprises a VL CDR3 having asequence selected from SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192 and 198 or a sequence comprising from 1 to 3 amino acid modifications relative to one of SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192 and 198.

4. The CAR of any preceding claim, wherein the antigen recognition domain comprises VL CDR1, 2and 3 sequences set forth in: (i) SEQ ID NOs: 4, 5 and 6 respectively;(ii) SEQ ID NOs: 10, 11 and 12 respectively;(iii) SEQ ID NOs: 16, 17 and 18 respectively;(iv) SEQ ID NOs: 22, 23 and 24 respectively;(v) SEQ ID NOs: 28, 29 and 30 respectively;(vi) SEQ ID NOs: 34, 35 and 36 respectively;(vii) SEQ ID NOs: 40, 41 and 42 respectively;(viii) SEQ ID NOs: 46, 47 and 48 respectively;(ix) SEQ ID NOs: 52, 53 and 54 respectively;(x) SEQ ID NOs: 58, 59 and 60 respectively;(xi) SEQ ID NOs: 64, 65 and 66 respectively;(xii) SEQ ID NOs: 70, 71 and 72 respectively;(xiii) SEQ ID NOs: 76, 77 and 78 respectively;(xiv) SEQ ID NOs: 82, 83 and 84 respectively;(xv) SEQ ID NOs: 88, 89 and 90 respectively;(xvi) SEQ ID NOs: 94, 95 and 96 respectively;(xvii) SEQ ID NOs: 100, 101 and 102 respectively;(xviii) SEQ ID NOs: 106, 107 and 108 respectively;(xix) SEQ ID NOs: 112, 113 and 114 respectively;(xx) SEQ ID NOs: 118, 119 and 120 respectively;(xxi) SEQ ID NOs: 124, 125 and 126 respectively;(xxii) SEQ ID NOs: 130, 131 and 132 respectively;(xxiii) SEQ ID NOs: 136, 137 and 138 respectively;(xxiv) SEQ ID NOs: 142, 143 and 144 respectively;(xxv) SEQ ID NOs: 148, 149 and 150 respectively;(xxvi) SEQ ID NOs: 154, 155 and 156 respectively;(xxvii) SEQ ID NOs: 160, 161 and 162 respectively;(xxviii) SEQ ID NOs: 166, 167 and 168 respectively;(xxix) SEQ ID NOs: 172, 173 and 174 respectively;(xxx) SEQ ID NOs: 178, 179 and 180 respectively;(xxxi) SEQ ID NOs: 184, 185 and 186 respectively;(xxxii) SEQ ID NOs: 190, 191 and 192 respectively; or(xxxiii) SEQ ID NOs: 196, 197 and 198 respectively;wherein one or more of said VL CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 amino acid modifications relative to an aforementioned CDR sequence.

5. The CAR of any preceding claim, wherein the antigen recognition domain is a single chainantibody (scFv).

6. The CAR of any preceding claim, wherein the antigen recognition domain comprises:(i) VH CDR 1, 2 and 3 sequences set forth in SEQ ID NOs: 1, 2 and 3 respectively andVL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 4, 5 and 6 respectively; (ii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 7, 8 and 9 respectivelyand VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 10, 11 and 12 respectively; (iii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 13, 14 and 15respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 16, 17 and 18 respectively; (iv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 19, 20 and 21respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 22, 23 and 24 respectively; (v) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 25, 26 and 27respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 28, 29 and 30 respectively;(vi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 31, 32 and 33respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 34, 35 and 36 respectively;(vii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 37, 38 and 39respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 40, 41 and 42 respectively;(viii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 43, 44 and 45respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 46, 47 and 48 respectively;(ix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 49, 50 and 51respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 52, 53 and 54 respectively;(x) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 55, 56 and 57respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 58, 59 and 60 respectively;(xi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 61, 62 and 63respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 64, 65 and 66 respectively;(xii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 67, 68 and 69respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 70, 71 and 72 respectively;(xiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 73, 74 and 75respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 76, 77 and 78 respectively;(xiv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 79, 80 and 81respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 82, 83 and 84 respectively;(xv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 85, 86 and 87respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 88, 89 and 90 respectively;(xvi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 91, 92 and 93respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 94, 95 and 96 respectively;(xvii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 97, 98 and 99respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 100, 101 and 102 respectively;(xviii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 103, 104 and 105respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 106, 107 and 108 respectively;(xix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 109, 110 and 111respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 112,113 and 114 respectively;(xx) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 115, 116 and 117respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 118, 119 and 120 respectively;(xxi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 121, 122 and 123respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 124, 125 and 126 respectively;(xxii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 127, 128 and 129respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 130, 131 and 132 respectively;(xxiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 133, 134 and 135respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 136, 137 and 138 respectively;(xxiv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 139, 140 and 141respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 142, 143 and 144 respectively;(xxv) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 145, 146 and 147respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 148, 149 and 150 respectively;(xxvi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 151, 152 and 153respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 154, 155 and 156 respectively;(xxvii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 157, 158 and 159respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 160, 161 and 162 respectively;(xxviii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 163, 164 and 165respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 166, 167 and 168 respectively;(xxix) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 169, 170 and 171respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 172, 173 and 174 respectively;(xxx) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 175, 176 and 177respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 178, 179 and 180 respectively; (xxxi) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 181, 182 and 183respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 184, 185 and 186 respectively; (xxxii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 187, 188 and 189respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 190, 191 and 192 respectively; or (xxxiii) VH CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 193, 194 and 195respectively and VL CDR1, 2 and 3 sequences set forth in SEQ ID NOs: 196, 197 and 198 respectively; wherein one or more of said CDR sequences of (i) to (xxxiii) optionally comprises from 1 to 3 amino acid modifications relative to an aforementioned CDR sequence.

7. The CAR of any preceding claim, wherein the antigen recognition domain comprises:(i) a VH domain comprising the sequence set forth in SEQ ID NO: 199, or a sequencehaving at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 200, or a sequence having at least 70% identity thereto; (ii) a VH domain comprising the sequence set forth in SEQ ID NO: 201, or asequence having at least 70% identity thereto, and a VL domain comprising thesequence as set forth in SEQ ID NO: 202, or a sequence having at least 70% identity thereto; (iii) a VH domain comprising the sequence set forth in SEQ ID NO: 203, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 204, or a sequence having at least 70% identity thereto; (iv) a VH domain comprising the sequence set forth in SEQ ID NO: 205, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 206, or a sequence having at least 70% identity thereto; (v) a VH domain comprising the sequence set forth in SEQ ID NO: 207, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 208, or a sequence having at least 70%identity thereto; (vi) a VH domain comprising the sequence set forth in SEQ ID NO: 209, or asequence having at least 70% identity thereto, and a VL domain comprising thesequence as set forth in SEQ ID NO: 210, or a sequence having at least 70% identity thereto;(vii) a VH domain comprising the sequence set forth in SEQ ID NO: 211, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 212, or a sequence having at least 70%identity thereto;(viii) a VH domain comprising the sequence set forth in SEQ ID NO: 213, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 214, or a sequence having at least 70% identity thereto;(ix) a VH domain comprising the sequence set forth in SEQ ID NO: 215, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 216, or a sequence having at least 70% identity thereto;(x) a VH domain comprising the sequence set forth in SEQ ID NO: 217, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 218, or a sequence having at least 70% identity thereto;(xi) a VH domain comprising the sequence set forth in SEQ ID NO: 219, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 220, or a sequence having at least 70% identity thereto;(xii) a VH domain comprising the sequence set forth in SEQ ID NO: 221, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 222, or a sequence having at least 70% identity thereto;(xiii) a VH domain comprising the sequence set forth in SEQ ID NO: 223, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 224, or a sequence having at least 70% identity thereto;(xiv) a VH domain comprising the sequence set forth in SEQ ID NO: 225, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 226, or a sequence having at least 70% identity thereto;(xv) a VH domain comprising the sequence set forth in SEQ ID NO: 227, or asequence having at least 70% identity thereto, and a VL domain comprising thesequence as set forth in SEQ ID NO: 228, or a sequence having at least 70% identity thereto;(xvi) a VH domain comprising the sequence set forth in SEQ ID NO: 229, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 230, or a sequence having at least 70% identity thereto;(xvii) a VH domain comprising the sequence set forth in SEQ ID NO: 231, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 232, or a sequence having at least 70% identity thereto;(xviii) a VH domain comprising the sequence set forth in SEQ ID NO: 233, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 234, or a sequence having at least 70% identity thereto;(xix) a VH domain comprising the sequence set forth in SEQ ID NO: 235, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 236, or a sequence having at least 70% identity thereto;(xx) a VH domain comprising the sequence set forth in SEQ ID NO: 237, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 238, or a sequence having at least 70%identity thereto;(xxi) a VH domain comprising the sequence set forth in SEQ ID NO: 239, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 240, or a sequence having at least 70% identity thereto;(xxii) a VH domain comprising the sequence set forth in SEQ ID NO: 241, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 242, or a sequence having at least 70% identity thereto;(xxiii) a VH domain comprising the sequence set forth in SEQ ID NO: 243, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 244, or a sequence having at least 70% identity thereto;(xxiv) a VH domain comprising the sequence set forth in SEQ ID NO: 245, or asequence having at least 70% identity thereto, and a VL domain comprising thesequence as set forth in SEQ ID NO: 246, or a sequence having at least 70% identity thereto;(xxv) a VH domain comprising the sequence set forth in SEQ ID NO: 247, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 248, or a sequence having at least 70% identity thereto;(xxvi) a VH domain comprising the sequence set forth in SEQ ID NO: 249, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 250, or a sequence having at least 70% identity thereto;(xxvii) a VH domain comprising the sequence set forth in SEQ ID NO: 251, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 252, or a sequence having at least 70% identity thereto;(xxviii) a VH domain comprising the sequence set forth in SEQ ID NO: 253, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 254, or a sequence having at least 70% identity thereto;(xxix) a VH domain comprising the sequence set forth in SEQ ID NO: 255, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 256, or a sequence having at least 70% identity thereto;(xxx) a VH domain comprising the sequence set forth in SEQ ID NO: 257, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 258, or a sequence having at least 70% identity thereto;(xxxi) a VH domain comprising the sequence set forth in SEQ ID NO: 259, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 260, or a sequence having at least 70% identity thereto;(xxxii) a VH domain comprising the sequence set forth in SEQ ID NO: 261, or asequence having at least 70% identity thereto, and a VL domain comprising the sequence as set forth in SEQ ID NO: 262, or a sequence having at least 70% identity thereto; or(xxxiii) a VH domain comprising the sequence set forth in SEQ ID NO: 263, or asequence having at least 70% identity thereto, and a VL domain comprising thesequence as set forth in SEQ ID NO: 264, or a sequence having at least 70% identity thereto.

8. The CAR of any preceding claim, wherein the antigen recognition domain comprises:(i) the sequence set forth in SEQ ID NO: 265 or a sequence having at least 70% identitythereto; (ii) the sequence set forth in SEQ ID NO: 266 or a sequence having at least 70%identity thereto; (iii) the sequence set forth in SEQ ID NO: 267 or a sequence having at least 70%identity thereto; (iv) the sequence set forth in SEQ ID NO: 268 or a sequence having at least 70%identity thereto; (v) the sequence set forth in SEQ ID NO: 269 or a sequence having at least 70%identity thereto; (vi) the sequence set forth in SEQ ID NO: 270 or a sequence having at least 70%identity thereto; (vii) the sequence set forth in SEQ ID NO: 271 or a sequence having at least 70%identity thereto; (viii) the sequence set forth in SEQ ID NO: 272 or a sequence having at least 70%identity thereto; (ix) the sequence set forth in SEQ ID NO: 273 or a sequence having at least 70%identity thereto; (x) the sequence set forth in SEQ ID NO: 274 or a sequence having at least 70%identity thereto; (xi) the sequence set forth in SEQ ID NO: 275 or a sequence having at least 70%identity thereto; (xii) the sequence set forth in SEQ ID NO: 276 or a sequence having at least 70%identity thereto; (xiii) the sequence set forth in SEQ ID NO: 277 or a sequence having at least 70%identity thereto; (xiv) the sequence set forth in SEQ ID NO: 278 or a sequence having at least 70%identity thereto; (xv) the sequence set forth in SEQ ID NO: 279 or a sequence having at least 70%identity thereto; (xvi) the sequence set forth in SEQ ID NO: 280 or a sequence having at least 70%identity thereto;(xvii) the sequence set forth in SEQ ID NO: 281 or a sequence having at least 70%identity thereto; (xviii) the sequence set forth in SEQ ID NO: 282 or a sequence having at least 70%identity thereto; (xix) the sequence set forth in SEQ ID NO: 283 or a sequence having at least 70%identity thereto; (xx) the sequence set forth in SEQ ID NO: 284 or a sequence having at least 70%identity thereto; (xxi) the sequence set forth in SEQ ID NO: 285 or a sequence having at least 70%identity thereto; (xxii) the sequence set forth in SEQ ID NO: 286 or a sequence having at least 70%identity thereto; (xxiii) the sequence set forth in SEQ ID NO: 287 or a sequence having at least 70%identity thereto; (xxiv) the sequence set forth in SEQ ID NO: 288 or a sequence having at least 70%identity thereto; (xxv) the sequence set forth in SEQ ID NO: 289 or a sequence having at least 70%identity thereto; (xxvi) the sequence set forth in SEQ ID NO: 290 or a sequence having at least 70%identity thereto; (xxvii) the sequence set forth in SEQ ID NO: 291 or a sequence having at least 70%identity thereto; (xxviii) the sequence set forth in SEQ ID NO: 292 or a sequence having at least 70%identity thereto; (xxix) the sequence set forth in SEQ ID NO: 293 or a sequence having at least 70%identity thereto; (xxx) the sequence set forth in SEQ ID NO: 294 or a sequence having at least 70%identity thereto; (xxxi) the sequence set forth in SEQ ID NO: 295 or a sequence having at least 70%identity thereto; (xxxii) the sequence set forth in SEQ ID NO: 296 or a sequence having at least 70%identity thereto; or (xxxiii) the sequence set forth in SEQ ID NO: 297 or a sequence having at least 70%identity thereto.

9. The CAR of any preceding claim, wherein the antigen recognition domain specifically binds tohuman and / or murine ASGPR.

10. The CAR of any preceding claim, comprising:a. an exodomain comprising the antigen recognition domain;b. a transmembrane domain; andc. an endodomain comprising an intracellular signalling domainoptionally wherein the CAR further comprises a hinge domain and / or one or more co- stimulatory domains,11. The CAR of claim 10, wherein:a. the hinge domain is selected from the hinge regions of CD28, CD8α, CD4, CD7,CH2CH3, an immunoglobulin, or a part or variant thereof, preferably wherein the CAR comprises a CD8α or CH2CH3 hinge region; b. the co-stimulatory domain is selected from the intracellular domains of CD28, ICOS,CD134 (OX40), CD137 (4-1BB), CD27, or TNFRSF25, or a part or variant thereof, preferably wherein the CAR comprises a CD28 co-stimulatory domain; c. the CAR comprises one or more transmembrane domains selected from thetransmembrane domains of CD28, ICOS, CD8α, CD4, CD134 (OX40), CD137 (4-1BB), CD3 zeta, CD45, CD9, CD16, CD22, CD33, CD64, CD80, CD86, CD154 or a part or variant thereof, preferably wherein the CAR comprises a CD28 or CD8α transmembrane domain; and / or d. the CAR comprises one or more intracellular signalling domains selected from the groupconsisting of the CD3 zeta signalling domain or any of its homologs, a CD3 polypeptide,a syk family tyrosine kinase, a src family tyrosine kinase, CD2, CD5, CD28, or a part or variant thereof, preferably wherein the CAR comprises the CD3 zeta signalling domain.

12. The CAR of claim 10 or 11, wherein the CAR comprises: a CD8α or CH2CH3 hinge domain, aCD28 or CD8α transmembrane domain, a CD28 co-stimulatory domain, and the CD3zeta signalling domain, wherein when the hinge domain is CD8α, the transmembrane domain is CD8α, and when the hinge domain is CH2CH3, the transmembrane domain is CD28.

13. The CAR of any preceding claim comprising the sequence set forth in any of SEQ ID NOs: 298 to363 or a sequence having at least 70% identity thereto.

14. The CAR of any preceding claim comprising a sequence encoded by the sequence set forth inany of SEQ ID NOs: 438, 439, 440, 441, 442 or 443 or a sequence having at least 70% identity to the sequence encoded by SEQ ID NO: 438, 439, 440, 441, 442 or 443 respectively.

15. A nucleic acid molecule comprising a nucleotide sequence encoding the CAR of any precedingclaim.

16. A vector comprising the nucleic acid molecule of claim 15, optionally further comprising a nucleicacid molecule encoding a FOXP3 polypeptide.

17. A cell comprising the CAR of any of claims 1 to 14, the nucleic acid molecule of claim 15 or thevector of claim 16, optionally wherein the cell is a regulatory T cell (Treg), or a precursor thereof,or an iPSC cell, or a production host cell, particularly wherein the cell further comprises an exogenous nucleic acid comprising a nucleotide sequence encoding a FOXP3 polypeptide.

18. A pharmaceutical composition comprising a cell of claim 17 or a vector of claim 16.

19. The cell of claim 17, or the pharmaceutical composition of claim 18, for use in therapy, particularlyadoptive cell transfer therapy.

20. The cell of claim 17 or the pharmaceutical composition of claim 18, for use in induction oftolerance to a liver transplant in a subject, or for use in the treatment and / or prevention of liver transplant rejection, liver graft-versus-host disease (GvHD), an autoimmune liver disease, or an inflammatory liver disorder in a subject, particularly wherein the cell is a Treg.

21. A method of inducing tolerance to a liver transplant in a subject, or treating and / or preventing livertransplant rejection, liver graft-versus-host disease (GvHD), an autoimmune liver disease, or an inflammatory liver disorder in a subject, which comprises the step of administering to the subject acell of claim 17 or a pharmaceutical composition of claim 18, particularly wherein the cell is aTreg.

22. The method according to any preceding claim, wherein the method comprises the following steps:(i) isolation or provision of a Treg-enriched sample from a subject;(ii) transduction or transfection of the Treg cells with a polynucleotide, a nucleic acidor a vector encoding a CAR according to any of claims 1 to 14; and (iii) administering the engineered Treg cells to the subject.

23. A method of making a cell of claim 17, the method comprising the step of introducing into the cellthe nucleic acid of claim 15 or the vector of claim 16, particularly wherein the cell is a Treg.

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