Anti-CD30 antibodies and chimeric antigen receptors containing them

Abstract

This specification discloses novel antibodies targeting CD30 for cancer treatment, their antigen-binding fragments, chimeric antigen receptors, and their applications. The antibodies of the present invention specifically bind to CD30, which is highly expressed in cancer cells (particularly hematological cancers), and have very low homology to the CDR sequences of conventional CD30-targeted antibodies, thus possessing a unique sequence. Cells expressing the anti-CD30 antibody or the chimeric antigen receptor containing the antigen-binding fragment of the present invention induce immune cell activity in response to CD30-positive cell lines, and are therefore useful as CAR immunotherapy agents.

Claims

1. Anti-CD30 antibodies or their antigen-binding fragments containing immunoglobulin heavy chain variable region domains and immunoglobulin light chain variable region domains: i) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, each comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; ii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26; iii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 41, SEQ ID NO: 42, and SEQ ID NO: 43; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 44, SEQ ID NO: 45, and SEQ ID NO: 46; iv) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66; v) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 81, SEQ ID NO: 82, and SEQ ID NO: 83; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86; vi) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, each comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NO: 104, SEQ ID NO: 105, and SEQ ID NO: 106, respectively; vii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 121, SEQ ID NO: 122, and SEQ ID NO: 123; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 124, SEQ ID NO: 125, and SEQ ID NO: 126; viiii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, each comprising the amino acid sequences of SEQ ID NO: 141, SEQ ID NO: 142, and SEQ ID NO: 143, respectively; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO: 146, respectively; ix) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 161, SEQ ID NO: 162, and SEQ ID NO: 163; and the light chain variable region domain comprises LC It comprises DR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each contain the amino acid sequences of SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO: 166; x) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186; or xi) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 201, SEQ ID NO: 202, and SEQ ID NO: 203; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 204, SEQ ID NO: 205, and SEQ ID NO:

206.

2. An anti-CD30 antibody or antigen-binding fragment thereof according to claim 1, comprising a heavy chain variable region domain and a light chain variable region domain: 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; viiii) 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 antigen-binding fragment thereof according to claim 1, wherein the anti-CD30 antibody or antigen-binding fragment thereof comprises an scFv, and the scFv comprises an amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 29, SEQ ID NO: 49, SEQ ID NO: 69, SEQ ID NO: 89, SEQ ID NO: 109, SEQ ID NO: 129, SEQ ID NO: 149, SEQ ID NO: 169, SEQ ID NO: 189, and SEQ ID NO:

209.

4. The antigen-binding fragments are Fab, Fab', and F(ab'). ２ Fv, scFV, or chemical F(ab') connected in a specific way ２ The anti-CD30 antibody or antigen-binding fragment thereof as described in claim 1.

5. A nucleic acid molecule encoding the anti-CD30 antibody or its antigen-binding fragment according to claim 1.

6. The nucleic acid molecule according to claim 5 comprises a nucleotide sequence selected from the following group: i) The nucleotide sequences of SEQ ID NO: 11, 12, 13, 14, 15, and 16, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; ii) The nucleotide sequences of SEQ ID NO: 31, 32, 33, 34, 35, and 36, where each of these nucleotide sequences 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, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; iv) The nucleotide sequence of SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, and SEQ ID NO: 76, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; v) The nucleotide sequences of SEQ ID NO: 91, 92, 93, 94, 95, and 96, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; vi) The nucleotide sequences of SEQ ID NO: 111, 112, 113, 114, 115, and 116, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; vii) The nucleotide sequences of SEQ ID NO: 131, 132, 133, 134, 135, and 136, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively; viiii) 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, where each of these nucleotide sequences 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, where the nucleotides Each of the sequences 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, where each of the nucleotide sequences 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, where each of these nucleotide sequences encodes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively.

7. The nucleic acid molecule according to claim 5 comprises a nucleotide sequence selected from the following group: i) The nucleotide sequence of SEQ ID NO: 17 and the nucleotide sequence of SEQ ID NO: 18, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; ii) The nucleotide sequence of SEQ ID NO: 37 and the nucleotide sequence of SEQ ID NO: 38, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; iii) The nucleotide sequence of Sequence ID No. 57 and the nucleotide sequence of Sequence ID No. 58, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; iv) The nucleotide sequence of SEQ ID NO: 77 and the nucleotide sequence of SEQ ID NO: 78, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; v) The nucleotide sequence of SEQ ID NO: 97 and the nucleotide sequence of SEQ ID NO: 98, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; vi) The nucleotide sequence of sequence number 117 and the nucleotide sequence of sequence number 118, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; vii) The nucleotide sequence of sequence number 137 and the nucleotide sequence of sequence number 138, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; viiii) The nucleotide sequence of sequence number 157 and the nucleotide sequence of sequence number 158, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; ix) The nucleotide sequence of sequence number 177 and the nucleotide sequence of sequence number 178, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; x) The nucleotide sequence of SEQ ID NO: 197 and the nucleotide sequence of SEQ ID NO: 198, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively; and xi) The nucleotide sequence of sequence number 217 and the nucleotide sequence of sequence number 218, where the nucleotide sequences encode the heavy chain variable region domain and the light chain variable region domain, respectively.

8. The nucleic acid molecule has the nucleotide sequence of SEQ ID NO: 19 and the nucleotide sequence of SEQ ID NO:

39. The nucleic acid molecule according to claim 5, comprising a nucleotide sequence selected from the group consisting of 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 scFv.

9. A CD30-specific chimeric antigen receptor comprising an anti-CD30 antibody or its antigen-binding fragment, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD30 antibody or its antigen-binding fragment includes a heavy chain variable region domain and a light chain variable region domain: i) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, each comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; ii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 24, SEQ ID NO: 25, and SEQ ID NO: 26; iii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 41, SEQ ID NO: 42, and SEQ ID NO: 43; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 44, SEQ ID NO: 45, and SEQ ID NO: 46; iv) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66; v) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 81, SEQ ID NO: 82, and SEQ ID NO: 83; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86; vi) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, each comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NO: 104, SEQ ID NO: 105, and SEQ ID NO: 106, respectively; vii) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 121, SEQ ID NO: 122, and SEQ ID NO: 123; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 124, SEQ ID NO: 125, and SEQ ID NO: 126; viiii) The heavy chain variable region domain includes HCDR1, HCDR2, and HCDR3, where HCDR1, HCDR2, and HCDR3 are each sequence number 141, sequence number 141, and sequence number 141, respectively. The light chain variable domain comprises the amino acid sequences of sequence 142 and sequence number 143; and the light chain variable domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of sequence number 144, sequence number 145, and sequence number 146; ix) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, each comprising the amino acid sequences of SEQ ID NO: 161, SEQ ID NO: 162, and SEQ ID NO: 163; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO: 166; x) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 181, SEQ ID NO: 182, and SEQ ID NO: 183; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO: 186; or xi) The heavy chain variable region domain comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1, HCDR2, and HCDR3 each comprise the amino acid sequences of SEQ ID NO: 201, SEQ ID NO: 202, and SEQ ID NO: 203; and the light chain variable region domain comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1, LCDR2, and LCDR3 each comprise the amino acid sequences of SEQ ID NO: 204, SEQ ID NO: 205, and SEQ ID NO:

206.

10. The CD30-specific chimeric antigen receptor according to claim 9, comprising a heavy chain variable region domain and a light chain variable region domain: 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; viiii) 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 anti-CD30 antibody or its antigen-binding fragment comprises an scFv, the scFv comprising 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, and a sequence A CD30-specific chimeric antigen receptor according to claim 9, comprising an amino acid sequence selected from the group consisting of the amino acid sequence of sequence number 69, the amino acid sequence of sequence number 89, the amino acid sequence of sequence number 109, the amino acid sequence of sequence number 129, the amino acid sequence of sequence number 149, the amino acid sequence of sequence number 169, the amino acid sequence of sequence number 189, and the amino acid sequence of sequence number 209.

12. The CD30-specific chimeric antigen receptor according to claim 9, wherein the CD30-specific chimeric antigen receptor comprises an amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 30, SEQ ID NO: 50, SEQ ID NO: 70, SEQ ID NO: 90, SEQ ID NO: 110, SEQ ID NO: 130, SEQ ID NO: 150, SEQ ID NO: 170, SEQ ID NO: 190, and SEQ ID NO:

210.

13. The CD30-specific chimeric antigen receptor according to claim 9, wherein the transmembrane domain is a protein selected from the group consisting of 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 according to claim 9, wherein the signaling domain comprises a functional signaling domain derived from at least one of 4-1BB, CD28, OX40, and CD3 zeta, or a combination thereof.

15. A nucleic acid molecule encoding a CD30-specific chimeric antigen receptor as described in claim 9.

16. Effector cells expressing the CD30-specific chimeric antigen receptor described in claim 9.

17. A pharmaceutical composition comprising the anti-CD30 antibody or its antigen-binding fragment as described in claim 1.

18. A method for treating a disease associated with CD30-expressing cells, comprising the step of administering the pharmaceutical composition described in claim 17 to a target body that requires it.

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