Anti-CD30 antibody and chimeric antigen receptor comprising thereof
Disclosed herein are a novel antibody and an antigen binding fragment thereof that targets CD30 to treat cancer, a chimeric antigen receptor, and a use thereof. The antibody, which binds specifically to CD30 that is highly expressed in cancer cells (specifically blood cancer), is very low in sequence homology with the CDR sequences of conventional CD30 targeting antibodies and thus has a unique sequence. Cells that express the chimeric antigen receptor including the anti-CD30 antibody or the antigen binding fragment responds to CD30-expressing positive cells to induce immune cell activity, thus finding advantageous applications as a CAR-immune cell product.
1 . An anti-CD30 antibody or an antigen binding fragment thereof, comprising an immunoglobulin heavy-chain variable region domain and an immunoglobulin light-chain variable region domain, wherein:
i) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 1, 2, and 3, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 4, 5, and 6, respectively;
ii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 21, 22, and 23, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 24, 25, and 26, respectively;
iii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 41, 42, and 43, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 44, 45, and 46, respectively;
iv) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 61, 62, and 63, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 65, and 66, respectively;
v) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 81, 82, and 83, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 84, 85, and 86, respectively;
vi) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 101, 102, and 103, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 104, 105, and 106, respectively;
vii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 121, 122, and 123, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 124, 125, and 126, respectively;
viii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 141, 142, and 143, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 144, 145, and 146, respectively;
ix) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 161, 162, and 163, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 164, 165, and 166, respectively;
x) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 181, 182, and 183, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 184, 185, and 186, respectively; or
xi) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 201, 202, and 203, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 204, 205, and 206, respectively.
2 . The anti-CD30 antibody or the antigen binding fragment thereof according to claim 1 , wherein the anti-CD30 antibody or the antigen binding fragment thereof comprises a heavy chain variable region domain and a light chain variable region domain, wherein:
i) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 7; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 8;
ii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 27; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 28;
iii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 47; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 48;
iv) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 67; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 68;
v) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 87; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 88;
vi) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 107; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 108;
vii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 127; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 128;
viii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 147; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 148;
ix) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 167; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 168;
x) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 187; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 188; or
xi) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 207; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 208.
3 . The anti-CD30 antibody or the antigen binding fragment thereof according to claim 1 , wherein the anti-CD30 antibody or the antigen binding fragment thereof comprises an scFv, wherein the scFv comprises an amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 9, the amino acid sequence of SEQ ID NO: 29, the amino acid sequence of SEQ ID NO: 49, the amino acid sequence of SEQ ID NO: 69, the amino acid sequence of SEQ ID NO: 89, the amino acid sequence of SEQ ID NO: 109, the amino acid sequence of SEQ ID NO: 129, the amino acid sequence of SEQ ID NO: 149, the amino acid sequence of SEQ ID NO: 169, the amino acid sequence of SEQ ID NO: 189, and the amino acid sequence of SEQ ID NO: 209.
4 . The anti-CD30 antibody or the antigen binding fragment thereof according to claim 1 , wherein the antigen binding fragment is a Fab, Fab′, F(ab′) 2 , Fv, scFv, or chemically linked F(ab′) 2 .
5 . A nucleic acid molecule encoding the anti-CD30 antibody or the antigen binding fragment thereof according to claim 1 .
6 . The nucleic acid molecule according to claim 5 , wherein the nucleic acid molecule comprises nucleotide sequences selected from the group consisting of:
i) the nucleotide sequence of SEQ ID NO: 11, the nucleotide sequence of SEQ ID NO: 12, the nucleotide sequence of SEQ ID NO: 13, the nucleotide sequence of SEQ ID NO: 14, the nucleotide sequence of SEQ ID NO: 15, and the nucleotide sequence of SEQ ID NO: 16, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
ii) the nucleotide sequence of SEQ ID NO: 31, the nucleotide sequence of SEQ ID NO: 32, the nucleotide sequence of SEQ ID NO: 33, the nucleotide sequence of SEQ ID NO: 34, the nucleotide sequence of SEQ ID NO: 35, and the nucleotide sequence of SEQ ID NO: 36, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
iii) the nucleotide sequence of SEQ ID NO: 51, the nucleotide sequence of SEQ ID NO: 52, the nucleotide sequence of SEQ ID NO: 53, the nucleotide sequence of SEQ ID NO: 54, the nucleotide sequence of SEQ ID NO: 55, and the nucleotide sequence of SEQ ID NO: 56, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
iv) the nucleotide sequence of SEQ ID NO: 71, the nucleotide sequence of SEQ ID NO: 72, the nucleotide sequence of SEQ ID NO: 73, the nucleotide sequence of SEQ ID NO: 74, the nucleotide sequence of SEQ ID NO: 75, and the nucleotide sequence of SEQ ID NO: 76, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
v) the nucleotide sequence of SEQ ID NO: 91, the nucleotide sequence of SEQ ID NO: 92, the nucleotide sequence of SEQ ID NO: 93, the nucleotide sequence of SEQ ID NO: 94, the nucleotide sequence of SEQ ID NO: 95, and the nucleotide sequence of SEQ ID NO: 96, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
vi) the nucleotide sequence of SEQ ID NO: 111, the nucleotide sequence of SEQ ID NO: 112, the nucleotide sequence of SEQ ID NO: 113, the nucleotide sequence of SEQ ID NO: 114, the nucleotide sequence of SEQ ID NO: 115, and the nucleotide sequence of SEQ ID NO: 116, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
vii) the nucleotide sequence of SEQ ID NO: 131, the nucleotide sequence of SEQ ID NO: 132, the nucleotide sequence of SEQ ID NO: 133, the nucleotide sequence of SEQ ID NO: 134, the nucleotide sequence of SEQ ID NO: 135, and the nucleotide sequence of SEQ ID NO: 136, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
viii) the nucleotide sequence of SEQ ID NO: 151, the nucleotide sequence of SEQ ID NO: 152, the nucleotide sequence of SEQ ID NO: 153, the nucleotide sequence of SEQ ID NO: 154, the nucleotide sequence of SEQ ID NO: 155, and the nucleotide sequence of SEQ ID NO: 156, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
ix) the nucleotide sequence of SEQ ID NO: 171, the nucleotide sequence of SEQ ID NO: 172, the nucleotide sequence of SEQ ID NO: 173, the nucleotide sequence of SEQ ID NO: 174, the nucleotide sequence of SEQ ID NO: 175, and the nucleotide sequence of SEQ ID NO: 176, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively;
x) the nucleotide sequence of SEQ ID NO: 191, the nucleotide sequence of SEQ ID NO: 192, the nucleotide sequence of SEQ ID NO: 193, the nucleotide sequence of SEQ ID NO: 194, the nucleotide sequence of SEQ ID NO: 195, and the nucleotide sequence of SEQ ID NO: 196, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; and
xi) the nucleotide sequence of SEQ ID NO: 211, the nucleotide sequence of SEQ ID NO: 212, the nucleotide sequence of SEQ ID NO: 213, the nucleotide sequence of SEQ ID NO: 214, the nucleotide sequence of SEQ ID NO: 215, and the nucleotide sequence of SEQ ID NO: 216, wherein the nucleotide sequence encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively.
7 . The nucleic acid molecule according to claim 5 , wherein the nucleic acid molecule comprises nucleotide sequences selected from the group consisting of:
i) the nucleotide sequence of SEQ ID NO: 17 and the nucleotide sequence of SEQ ID NO: 18, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
ii) the nucleotide sequence of SEQ ID NO: 37 and the nucleotide sequence of SEQ ID NO: 38, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
iii) the nucleotide sequence of SEQ ID NO: 57 and the nucleotide sequence of SEQ ID NO: 58, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
iv) the nucleotide sequence of SEQ ID NO: 77 and the nucleotide sequence of SEQ ID NO: 78, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
v) the nucleotide sequence of SEQ ID NO: 97 and the nucleotide sequence of SEQ ID NO: 98, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
vi) the nucleotide sequence of SEQ ID NO: 117 and the nucleotide sequence of SEQ ID NO: 118, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
vii) the nucleotide sequence of SEQ ID NO: 137 and the nucleotide sequence of SEQ ID NO: 138, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
viii) the nucleotide sequence of SEQ ID NO: 157 and the nucleotide sequence of SEQ ID NO: 158, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
ix) the nucleotide sequence of SEQ ID NO: 177 and the nucleotide sequence of SEQ ID NO: 178, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively;
x) the nucleotide sequence of SEQ ID NO: 197 and the nucleotide sequence of SEQ ID NO: 198, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively; and
xi) the nucleotide sequence of SEQ ID NO: 217 and the nucleotide sequence of SEQ ID NO: 218, wherein the nucleotide sequences encode the heavy chain variable domain and the light chain variable domain, respectively.
8 . The nucleic acid molecule according to claim 5 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of the nucleotide sequence of SEQ ID NO: 19, the nucleotide sequence of SEQ ID NO: 39, the nucleotide sequence of SEQ ID NO: 59, the nucleotide sequence of SEQ ID NO: 79, the nucleotide sequence of SEQ ID NO: 99, the nucleotide sequence of SEQ ID NO: 119, the nucleotide sequence of SEQ ID NO: 139, the nucleotide sequence of SEQ ID NO: 159, the nucleotide sequence of SEQ ID NO: 179, the nucleotide sequence of SEQ ID NO: 199, and the nucleotide sequence of SEQ ID NO: 219, wherein the nucleotide sequence encodes an scFv.
9 . A CD30-specific chimeric antigen receptor, comprising:
an anti-CD30 antibody or an antigen binding fragment thereof;
a transmembrane domain; and
an intracellular signaling domain,
wherein the anti-CD30 antibody or the antigen binding fragment thereof comprises a heavy chain variable region domain and a light chain variable region domain, wherein:
i) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 1, 2, and 3, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 4, 5, and 6, respectively;
ii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 21, 22, and 23, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 24, 25, and 26, respectively;
iii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 41, 42, and 43, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 44, 45, and 46, respectively;
iv) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 61, 62, and 63, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 65, and 66, respectively;
v) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 81, 82, and 83, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 84, 85, and 86, respectively;
vi) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 101, 102, and 103, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 104, 105, and 106, respectively;
vii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 121, 122, and 123, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 124, 125, and 126, respectively;
viii) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 141, 142, and 143, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 144, 145, and 146, respectively;
ix) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 161, 162, and 163, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 164, 165, and 166, respectively;
x) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 181, 182, and 183, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 184, 185, and 186, respectively; or
xi) the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequence of SEQ ID NO: 201, 202, and 203, respectively; and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 204, 205, and 206, respectively.
10 . The CD30-specific chimeric antigen receptor of claim 9 , wherein the anti-CD30 antibody or the antigen binding fragment thereof comprises a heavy chain variable region domain and a light chain variable region domain, wherein:
i) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 7; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 8;
ii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 27; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 28;
iii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 47; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 48;
iv) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 67; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 68;
v) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 87; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 88;
vi) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 107; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 108;
vii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 127; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 128;
viii) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 147; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 148;
ix) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 167; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 168;
x) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 187; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 188; or
xi) the heavy-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 207; and the light-chain variable region domain comprises the amino acid sequence of SEQ ID NO: 208.
11 . The CD30-specific chimeric antigen receptor of claim 9 , wherein the anti-CD30 antibody or the antigen binding fragment thereof comprises an scFv, wherein the scFv comprises an amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 9, the amino acid sequence of SEQ ID NO: 29, the amino acid sequence of SEQ ID NO: 49, the amino acid sequence of SEQ ID NO: 69, the amino acid sequence of SEQ ID NO: 89, the amino acid sequence of SEQ ID NO: 109, the amino acid sequence of SEQ ID NO: 129, the amino acid sequence of SEQ ID NO: 149, the amino acid sequence of SEQ ID NO: 169, the amino acid sequence of SEQ ID NO: 189, and the amino acid sequence of SEQ ID NO: 209.
12 . The CD30-specific chimeric antigen receptor of claim 9 , wherein the CD30-specific chimeric antigen receptor comprises an scFv CAR, wherein the scFv CAR comprises an amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 10, the amino acid sequence of SEQ ID NO: 30, the amino acid sequence of SEQ ID NO: 50, the amino acid sequence of SEQ ID NO: 70, the amino acid sequence of SEQ ID NO: 90, the amino acid sequence of SEQ ID NO: 110, the amino acid sequence of SEQ ID NO: 130, the amino acid sequence of SEQ ID NO: 150, the amino acid sequence of SEQ ID NO: 170, the amino acid sequence of SEQ ID NO: 190, and the amino acid sequence of SEQ ID NO: 210.
13 . The CD30-specific chimeric antigen receptor of claim 9 , wherein the transmembrane domain is the transmembrane domain of a protein selected from the group consisting of a T-cell receptor, CD27, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, and CD154.
14 . The CD30-specific chimeric antigen receptor of claim 9 , wherein the signaling domain comprises a functional signaling domain from at least one of 4-1BB, CD28, OX40, and CD3 zeta.
15 . A nucleic acid molecule encoding the CD30-specific chimeric antigen receptor of claim 9 .
16 . An effector cell expressing the CD30-specific chimeric antigen receptor of claim 9 .
17 . A pharmaceutical composition comprising the anti-CD30 antibody or antigen-binding fragment of claim 1 .
18 . A method for treating a disease related with a cell over-expressing CD30, the method comprising:
a step of administering the pharmaceutical composition of claim 17 to a subject in need thereof.