ANTI-CD307E SINGLE-DOMAIN ANTIBODIES, USES THEREOF IN CAR T-CELL AND FOR THE TREATMENT OF DISEASES

1 . A single domain antibody (sdAb) comprising a FcRH5 binding domain.

2 . The sdAb according to claim 1 wherein the FcRH5 binding domain comprises:

complementarity determining regions (CDRs)

with the following sequences:

CDR1-

(SEQ ID NO: 1)

RSSFSNNA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 3)

NTIPFRSA;

or

(ii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 4)

GFTFSNYA

CDR2-

(SEQ ID NO: 5)

INSDGGTA

CDR3-

(SEQ ID NO: 6)

AANRGFCAGVRCLEYQY;

or

(iii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 7)

GRTFSINA

CDR2-

(SEQ ID NO: 8)

IGGSGRVSST

CDR3-

(SEQ ID NO: 9)

AARRDYLPFPPESYDY;

or

(iv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 7)

GRTFSINA

CDR2-

(SEQ ID NO: 8)

IGGSGRVSST

CDR3-

(SEQ ID NO: 10)

AAGRRTSTNGGDYDY;

or

(v)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 7)

GRTFSINA

CDR2-

(SEQ ID NO: 11)

ISRSGGAT

CDR3-

(SEQ ID NO: 12)

AGTRRAFSTGLRDYDY;

or

(vi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 13)

GRTFSNST

CDR2-

(SEQ ID NO: 14)

ISWSGGTY

CDR3-

(SEQ ID NO: 15)

AAARKGWSTRGDDYDY;

or

(vii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 16)

GRTYNNYA

CDR2-

(SEQ ID NO: 17)

ISRSGGMT

(viii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 19)

GRTFSSYA

CDR2-

(SEQ ID NO: 20)

ISRIGGVT

CDR3-

(SEQ ID NO: 21)

AAAGLVSISTTPNDYDY;

or

(ix)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 24)

NAIPFRL;

or

(x)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 25)

RNIFSLNP

CDR2-

(SEQ ID NO: 26)

ITDGGST

CDR3-

(SEQ ID NO: 27)

NRVGGLQTWA;

or

(xi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 30)

AAGRRFSTSSRDYDI;

or

(xii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 31)

GRTFDSRP

CDR2-

(SEQ ID NO: 32)

VSWRGEST

CDR3-

(SEQ ID NO: 33)

AAGEPYSGTYYYRGRDYDY;

(xiii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 34)

GRTFSMYA

CDR2-

(SEQ ID NO: 35)

ISGSARIT

CDR3-

(SEQ ID NO: 36)

AASSTYTSTSGSSYNY;

or

(xiv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 39)

NALGGFVPSYG;

or

(xv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 155)

GRTSSRAA

CDR2-

(SEQ ID NO: 156)

ISWSGGTT

CDR3-

(SEQ ID NO: 157)

AAARIFTTARNDYDH;

or

(xvi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 186)

NTIPFRLS;

or

(xvii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 160)

GNIFRLNA

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 186)

NTIPFRLS;

or

(xviii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 1)

RSSFSNNA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 187)

NTIPVRSA;

or

(xix)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 188)

NTIPCRSA;

or

(xx)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 161)

GSSFRLNG

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 189)

NTIPFSRA;

or

(xxi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 162)

GRSVSINA

CDR2-

(SEQ ID NO: 176)

IDRSGNT

CDR3-

(SEQ ID NO: 190)

NTIPYSDS;

or

(xxii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 19)

GRTFSSYA

CDR2-

(SEQ ID NO: 177)

IDGIGGIT

CDR3-

(SEQ ID NO: 3)

NTIPFRSA;

or

(xxiii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 1)

RSSFSNNA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 191)

NAIPFRSA;

or

(xxiv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 163)

GNNFRLNA

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 192)

NAIPFRPS;

or

(xxv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 193)

NAIPFRRS;

or

(xxvi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 164)

ERIFRINA

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 193)

NAIPFRRS;

or

(xxvii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 165)

GFTFSTYW

CDR2-

(SEQ ID NO: 178)

IDNGGGTT

CDR3-

(SEQ ID NO: 194)

NALPFRLS;

or

(xxviii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 195)

NATPFRLS;

or

(xxix)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 179)

ITRGGNT

CDR3-

(SEQ ID NO: 196)

NSIPFRLS;

or

(xxx)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 166)

GNIFRING

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 197)

NAIPFRIS;

or

(xxxi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 163)

GNNFRLNA

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 198)

NAIPFRLY;

or

(xxxii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 165)

GFTFSTYW

CDR2-

(SEQ ID NO: 178)

IDNGGGTT

CDR3-

(SEQ ID NO: 199)

KAIPFRLS;

or

(xxiii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 167)

GSSFSNNA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 3)

NTIPFRSA;

or

(xxxiv)

CDRs with the following sequences: 

CDR1-

(SEQ ID NO: 165)

GFTFSTYW

CDR2-

(SEQ ID NO: 178)

IDNGGGTT

CDR3-

(SEQ ID NO: 3)

NTIPFRSA;

or

(xxxv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 160)

GNIFRLNA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 3)

NTIPFRSA;

or

(xxxvi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 168)

RSSFGNNA

CDR2-

(SEQ ID NO: 2)

ITKGGVT

CDR3-

(SEQ ID NO: 3)

NTIPFRSA;

or

(xxxvii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 169)

GRTFSTYG

CDR2-

(SEQ ID NO: 11)

ISRSGGAT

CDR3-

(SEQ ID NO: 12)

AGTRRAFSTGLRDYDY;

or

(xxxviii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 170)

GTIERNNA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 200)

AAGRRFSTRSRDYDY;

or

(xxxix)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 201)

AAGRRFSTSSRDYDY;

or

(xl)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 202)

AAGRRFSTGSRDYDI;

or

(xli)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 19)

GRTFSSYA

CDR2-

(SEQ ID NO: 179)

ISQFGGVTT

CDR3-

(SEQ ID NO: 202)

AAGRRFSTGSRDYDI;

or

(xlii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 203)

AGGRRFSTSSRDYDI;

or

(xliii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 204)

AAGRRFSTSSREYDI;

or

(xliv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 180)

IGMVGGLP

CDR3-

(SEQ ID NO: 205)

AAGRRLSTSSRDYDI;

or

(xlv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 181)

ISRGGGVS

CDR3-

(SEQ ID NO: 206)

AAGLRFSTGSRDYDI;

or

(xlvi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 171)

GRTFRRYA

CDR2-

(SEQ ID NO: 17)

ISRSGGMT

CDR3-

(SEQ ID NO: 207)

AAYVGGFSTTRRDYAY;

or

(xlvii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 13)

GRTFSNST

CDR2-

(SEQ ID NO: 156)

ISWSGGTT

CDR3-

(SEQ ID NO: 15)

AAARKGWSTRGDDYDY;

or

(xlviii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 172)

GRTVI

CDR2-

(SEQ ID NO: 182)

SSGSGGVT

CDR3-

(SEQ ID NO: 208)

AAALTWSTRPSDFTS;

or

(xlix)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 172)

GRTVI

CDR2-

(SEQ ID NO: 183)

SNWSGGVT

CDR3-

(SEQ ID NO: 18)

AAYVGGFSTARRDYSY;

or

(l)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 7)

GRTFSINA

CDR2-

(SEQ ID NO: 17)

ISRSGGMT

CDR3-

(SEQ ID NO: 18)

AAYVGGFSTARRDYSY;

or

(li)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 173)

GRTFSRYA

CDR2-

(SEQ ID NO: 184)

INGSGGT

CDR3-

(SEQ ID NO: 209)

AAARIFTTTRNEYDH;

or

(lii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 173)

GRTFSRYA

CDR2-

(SEQ ID NO: 184)

INGSGGT

CDR3-

(SEQ ID NO: 209)

AAARIFTTTRNEYDH;

or

(liii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 165)

GFTFSTYW

CDR2-

(SEQ ID NO: 178)

IDNGGGTT

CDR3-

(SEQ ID NO: 210)

AAARIFSTARNDYDH;

or

(liv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 211)

AGGRIFRTSSRDYDI;

or

(lv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 212)

AAARFFTTARNDYDH;

or

(lvi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 213)

NALGGFVPNYG;

or

(lvii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 213)

NALGGFVPNYG;

or

(lviii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 214)

NALGGFVPNDG;

or

(lix)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 163)

GNNFRLNA

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 215)

NALGGFAPNYG;

or

(lx)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 216)

NALGGFVPNYV;

or

(lxi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 174)

GRSFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 217)

NALGGFVLNYG;

or

(lxii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 218)

NALGGLVPNYG;

or

(lxiii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 219)

NALGGFLPNYG;

or

(lxiv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 220)

NALGGFVTNYG;

or

(lxv)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 37)

GSIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 220)

NALGGFVTNYG;

or

(lxvi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 222)

GRTV

CDR2-

(SEQ ID NO: 185)

ITRGGST

CDR3-

(SEQ ID NO: 213)

NALGGFVPNYG;

or

(lxvii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 39)

NALGGFVPSYG;

or

(lxviii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 163)

GNNFRLNA

CDR2-

(SEQ ID NO: 23)

ITSGGNT

CDR3-

(SEQ ID NO: 39)

NALGGFVPSYG;

or

(lxix)

CDR1-

(SEQ ID NO: 22)

GNIFRLNG

CDR2-

ITSGGST

(SEQ ID NO: 38)

CDR3-

(SEQ ID NO: 39)

NALGGFVPSYG;

or

(lxx)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 28)

GRSFSNYG

CDR2-

(SEQ ID NO: 29)

IGMVGGLT

CDR3-

(SEQ ID NO: 39)

NALGGFVPSYG;

or

(lxxi)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 175)

GNIFSINA

CDR2-

(SEQ ID NO: 38)

ITSGGST

CDR3-

(SEQ ID NO: 39)

NALGGFVPSYG;

or

(lxxii)

CDRs with the following sequences:

CDR1-

(SEQ ID NO: 165)

GFTFSTYW

CDR2-

(SEQ ID NO: 178)

IDNGGGTT

CDR3-

(SEQ ID NO: 221)

ARNPTRGWYSTDY.

optionally wherein one or more of the CDRs comprises one, two or three amino acid mutations.

3 . The sdAb according to claim 2 , wherein the FcRH5 binding domain comprises:

(i) a variable heavy chain domain antibody (VHH) having the sequence shown as SEQ ID NO: 40 or a variant having at least 80% sequence identity thereto; or

(ii) a VHH having the sequence shown as SEQ ID NO: 41 or a variant having at least 80% sequence identity thereto; or

(iii) a VHH having the sequence shown as SEQ ID NO: 42 or a variant having at least 80% sequence identity thereto; or

(iv) a VHH having the sequence shown as SEQ ID NO: 43 or a variant having at least 80% sequence identity thereto; or

(v) a VHH having the sequence shown as SEQ ID NO: 44 or a variant having at least 80% sequence identity thereto; or

(vi) a VHH having the sequence shown as SEQ ID NO: 45 or a variant having at least 80% sequence identity thereto; or

(vii) a VHH having the sequence shown as SEQ ID NO: 46 or a variant having at least

(viii) a VHH having the sequence shown as SEQ ID NO: 47 or a variant having at least 80% sequence identity thereto; or

(ix) a VHH having the sequence shown as SEQ ID NO: 48 or a variant having at least 80% sequence identity thereto; or

(x) a VHH having the sequence shown as SEQ ID NO: 49 or a variant having at least 80% sequence identity thereto; or

(xi) a VHH having the sequence shown as SEQ ID NO: 50 or a variant having at least 80% sequence identity thereto; or

(xii) a VHH having the sequence shown as SEQ ID NO: 51 or a variant having at least 80% sequence identity thereto; or

(xiii) a VHH having the sequence shown as SEQ ID NO: 52 or a variant having at least 80% sequence identity thereto; or

(xiv) a VHH having the sequence shown as SEQ ID NO: 53 or a variant having at least 80% sequence identity thereto;

(xv) a VHH having the sequence shown as SEQ ID NO: 158 or a variant having at least 80% sequence identity thereto; or

(xvi) a VHH having the sequence shown as SEQ ID NO: 223 or a variant having at least 80% sequence identity thereto; or

(xvii) a VHH having the sequence shown as SEQ ID NO: 224 or a variant having at least 80% sequence identity thereto; or

(xviii) a VHH having the sequence shown as SEQ ID NO: 225 or a variant having at least 80% sequence identity thereto; or

(xvix) a VHH having the sequence shown as SEQ ID NO: 226 or a variant having at least 80% sequence identity thereto; or

(xx) a VHH having the sequence shown as SEQ ID NO: 227 or a variant having at least 80% sequence identity thereto; or

(xxi) a VHH having the sequence shown as SEQ ID NO: 228 or a variant having at least 80% sequence identity thereto; or

(xxii) a VHH having the sequence shown as SEQ ID NO: 229 or a variant having at least 80% sequence identity thereto; or

(xxiii) a VHH having the sequence shown as SEQ ID NO: 230 or a variant having at least 80% sequence identity thereto; or

(xxiv) a VHH having the sequence shown as SEQ ID NO: 231 or a variant having at least (xxv) a VHH having the sequence shown as SEQ ID NO: 232 or a variant having at least 80% sequence identity thereto; or

(xxvi) a VHH having the sequence shown as SEQ ID NO: 233 or a variant having at least 80% sequence identity thereto; or

(xxvii) a VHH having the sequence shown as SEQ ID NO: 234 or a variant having at least 80% sequence identity thereto; or

(xxviii) a VHH having the sequence shown as SEQ ID NO: 235 or a variant having at least 80% sequence identity thereto; or

(xxix) a VHH having the sequence shown as SEQ ID NO: 236 or a variant having at least 80% sequence identity thereto; or

(xxx) a VHH having the sequence shown as SEQ ID NO: 237 or a variant having at least 80% sequence identity thereto; or

(xxxi) a VHH having the sequence shown as SEQ ID NO: 238 or a variant having at least 80% sequence identity thereto; or

(xxxii) a VHH having the sequence shown as SEQ ID NO: 239 or a variant having at least 80% sequence identity thereto; or

(xxxiii) a VHH having the sequence shown as SEQ ID NO: 240 or a variant having at least 80% sequence identity thereto; or

(xxxiv) a VHH having the sequence shown as SEQ ID NO: 241 or a variant having at least 80% sequence identity thereto; or

(xxxv) a VHH having the sequence shown as SEQ ID NO: 242 or a variant having at least 80% sequence identity thereto; or

(xxxvi) a VHH having the sequence shown as SEQ ID NO: 243 or a variant having at least 80% sequence identity thereto; or

(xxxvii) a VHH having the sequence shown as SEQ ID NO: 244 or a variant having at least 80% sequence identity thereto; or

(xxxviii) a VHH having the sequence shown as SEQ ID NO: 245 or a variant having at least 80% sequence identity thereto; or

(xxxix) a VHH having the sequence shown as SEQ ID NO: 246 or a variant having at least 80% sequence identity thereto; or

(xl) a VHH having the sequence shown as SEQ ID NO: 247 or a variant having at least 80% sequence identity thereto; or

(xli) a VHH having the sequence shown as SEQ ID NO: 248 or a variant having at least (xlii) a VHH having the sequence shown as SEQ ID NO: 249 or a variant having at least 80% sequence identity thereto; or

(xliii) a VHH having the sequence shown as SEQ ID NO: 250 or a variant having at least 80% sequence identity thereto; or

(xliv) a VHH having the sequence shown as SEQ ID NO: 251 or a variant having at least 80% sequence identity thereto; or

(xlv) a VHH having the sequence shown as SEQ ID NO: 252 or a variant having at least 80% sequence identity thereto; or

(xlvi) a VHH having the sequence shown as SEQ ID NO: 253 or a variant having at least 80% sequence identity thereto; or

(xlvii) a VHH having the sequence shown as SEQ ID NO: 254 or a variant having at least 80% sequence identity thereto; or

(xlviii) a VHH having the sequence shown as SEQ ID NO: 255 or a variant having at least 80% sequence identity thereto; or

(xlix) a VHH having the sequence shown as SEQ ID NO: 256 or a variant having at least 80% sequence identity thereto; or

(1) a VHH having the sequence shown as SEQ ID NO: 257 or a variant having at least 80% sequence identity thereto; or

(li) a VHH having the sequence shown as SEQ ID NO: 258 or a variant having at least 80% sequence identity thereto; or

(lii) a VHH having the sequence shown as SEQ ID NO: 259 or a variant having at least 80% sequence identity thereto; or

(liii) a VHH having the sequence shown as SEQ ID NO: 260 or a variant having at least 80% sequence identity thereto; or

(liv) a VHH having the sequence shown as SEQ ID NO: 261 or a variant having at least 80% sequence identity thereto; or

(lv) a VHH having the sequence shown as SEQ ID NO: 262 or a variant having at least 80% sequence identity thereto; or

(lvi) a VHH having the sequence shown as SEQ ID NO: 263 or a variant having at least 80% sequence identity thereto; or

(lvii) a VHH having the sequence shown as SEQ ID NO: 264 or a variant having at least 80% sequence identity thereto; or

(lviii) a VHH having the sequence shown as SEQ ID NO: 265 or a variant having at least

(lix) a VHH having the sequence shown as SEQ ID NO: 266 or a variant having at least 80% sequence identity thereto; or

(lx) a VHH having the sequence shown as SEQ ID NO: 267 or a variant having at least 80% sequence identity thereto; or

(lxi) a VHH having the sequence shown as SEQ ID NO: 268 or a variant having at least 80% sequence identity thereto; or

(lxii) a VHH having the sequence shown as SEQ ID NO: 269 or a variant having at least 80% sequence identity thereto; or

(lxiii) a VHH having the sequence shown as SEQ ID NO: 270 or a variant having at least 80% sequence identity thereto; or

(lxiv) a VHH having the sequence shown as SEQ ID NO: 271 or a variant having at least 80% sequence identity thereto; or

(lxv) a VHH having the sequence shown as SEQ ID NO: 272 or a variant having at least 80% sequence identity thereto; or

(lxvi) a VHH having the sequence shown as SEQ ID NO: 273 or a variant having at least 80% sequence identity thereto; or

(lxvii) a VHH having the sequence shown as SEQ ID NO: 274 or a variant having at least 80% sequence identity thereto; or

(lxviii) a VHH having the sequence shown as SEQ ID NO: 275 or a variant having at least 80% sequence identity thereto; or

(lxix) a VHH having the sequence shown as SEQ ID NO: 276 or a variant having at least 80% sequence identity thereto; or

(lxx) a VHH having the sequence shown as SEQ ID NO: 277 or a variant having at least 80% sequence identity thereto; or

(lxxi) a VHH having the sequence shown as SEQ ID NO: 278 or a variant having at least 80% sequence identity thereto; or

(lxxii) a VHH having the sequence shown as SEQ ID NO: 279 or a variant having at least 80% sequence identity thereto; or

(lxxiii) a VHH having the sequence shown as SEQ ID NO: 280 or a variant having at least 80% sequence identity thereto; or

(lxxiv) a VHH having the sequence shown as SEQ ID NO: 281 or a variant having at least 80% sequence identity thereto; or

(lxxv) a VHH having the sequence shown as SEQ ID NO: 282 or a variant having at least (lxxvi) a VHH having the sequence shown as SEQ ID NO: 283 or a variant having at least 80% sequence identity thereto; or

(lxxvii) a VHH having the sequence shown as SEQ ID NO: 284 or a variant having at least 80% sequence identity thereto; or

(lxxviii) a VHH having the sequence shown as SEQ ID NO: 285 or a variant having at least 80% sequence identity thereto; or

(lxxix) a VHH having the sequence shown as SEQ ID NO: 286 or a variant having at least 80% sequence identity thereto; or

(lxxx) a VHH having the sequence shown as SEQ ID NO: 287 or a variant having at least 80% sequence identity thereto; or

(lxxxi) a VHH having the sequence shown as SEQ ID NO: 288 or a variant having at least 80% sequence identity thereto.

4 . The sdAb according to claim 2 , wherein the sdAb is a humanised sdAb.

5 . A FcRH5 binding molecule comprising the sdAb according to claim 2 , wherein the FcRH5 binding molecule is selected from an antibody conjugate, a chimeric antigen receptor (CAR), or an immune cell engager.

6 . A CAR comprising the sdAb according to claim 2 .

7 . The CAR according claim 6 , which comprises the sequence selected from the group comprising SEQ ID NO: 76-SEQ ID NO: 89, SEQ ID NO: 159 and SEQ ID NO: 289-SEQ ID NO: 354, or a variant thereof which has at least 80% sequence identity thereto but retains the capacity to i) bind FcRH5 and ii) induce T cell signalling.

8 . An immune cell engager molecule which comprises:

(i) a first domain which comprises a sdAb according to claim 2 ; and

(ii) a second domain capable of activating a T cell.

9 . A polynucleotide comprising a nucleic acid sequence encoding an sdAb according to claim 2 , or encoding a CAR comprising the sdAb, or encoding an immune cell engagement molecule comprising the sdAb.

10 . A vector which comprises a polynucleotide according to claim 9 .

11 . A cell which comprises a CAR according to claim 6 , or comprises a polynucleotide comprising a nucleotide sequence encoding the CAR, or comprises a vector that comprises the polynucleotide.

12 . A pharmaceutical composition which comprises a sdAb according to claim 2 , or an FcRH5 binding molecule that comprises the sdAb, or an immune cell engager molecule that comprises the sdAb, or, a polynucleotide that comprises a nucleic acid sequence encoding the sdAb, or a vector that comprises the polynucleotide, or a cell that comprises the polynucleotide or the vector, together with a pharmaceutically acceptable carrier, diluent or excipient.

13 . (canceled)

14 . A method for treating a disease which comprises the step of administering to a subject the sdAb according to claim 2 , an FcRH5 binding molecule that comprises the sdAb, an immune cell engager molecule that comprises the sdAb, a polynucleotide that comprises a nucleic acid sequence encoding the sdAb, a vector that comprises the polynucleotide, a cell that comprises the polynucleotide or the vector.

15 . (canceled)

16 . The method according to claim 14 , wherein the disease is a B cell malignancy or a plasma cell disorder.

17 . The method according to claim 16 , wherein the a B cell malignancy or plasma cell disorder is selected from the list comprising: leukaemia, hairy cell leukaemia, chronic lymphocytic leukaemia, non-Hodgkins lymphoma, mantle cell lymphoma, EBV-associated lymphoma (Burkitt), lymphoplasmacytic lymphoma, plasmacytoma, solitary plasmocytoma, extramedullary plasmocytoma, plasma cell leukemia, multiple myeloma, macroglobulinemia, amyloidosis, Waldenstrom's macroglobulinemia, solitary bone plasmacytoma, extramedullary plasmacytoma, osteosclerotic myeloma, heavy chain diseases, monoclonal gammopathy of undetermined significance (MGUS), non-IgM MGUS, IgM MGUS, light chain MGUS and smoldering multiple myeloma.

18 . The method according to claim 16 , wherein the B cell malignancy or plasma cell disorder is multiple myeloma.

19 . The FcRH5 binding molecule that comprises a T cell engager molecule, a gamma delta T cell engager molecule, a natural killer (NK) T cell engager molecule, or a NK cell engager molecule.

20 . The immune cell engager molecule according to claim 8 which further comprises:

(iii) a third domain capable of co-activating a T cell.