Search

CN-121991231-A - Antibody or antigen binding fragment specifically binding trop2

CN121991231ACN 121991231 ACN121991231 ACN 121991231ACN-121991231-A

Abstract

The invention discloses an antibody or antigen binding fragment specifically binding trop < 2 >, which comprises heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 amino acid sequence is shown as SEQ ID NO.1, the HCDR2 amino acid sequence is shown as SEQ ID NO.2, the HCDR3 amino acid sequence is shown as SEQ ID NO.3, the LCDR1 amino acid sequence is shown as SEQ ID NO.4, the LCDR2 amino acid sequence is shown as SEQ ID NO.5, and the LCDR3 amino acid sequence is shown as SEQ ID NO. 6. The invention can detect the expression condition of trop < 2 > in human breast cancer and pancreatic cancer cell membrane tissue samples by an immunohistochemical method, and the accompanying diagnostic kit for humanized trop < 2 > antibody coupled drugs has the advantages of assisting accurate medication and avoiding ineffective treatment.

Inventors

  • CHEN YUNZHAO
  • YU JIE
  • WANG WENJIE
  • ZHANG XIN

Assignees

  • 浙江省人民医院

Dates

Publication Date
20260508
Application Date
20260409

Claims (10)

  1. 1. An antibody or antigen binding fragment specifically binding trop's 2, wherein the antibody or antigen binding fragment comprises heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 amino acid sequence is shown as SEQ ID No.1, the HCDR2 amino acid sequence is shown as SEQ ID No.2, the HCDR3 amino acid sequence is shown as SEQ ID No.3, the LCDR1 amino acid sequence is shown as SEQ ID No.4, the LCDR2 amino acid sequence is shown as SEQ ID No.5, and the LCDR3 amino acid sequence is shown as SEQ ID No. 6.
  2. 2. An antibody or antigen-binding fragment that specifically binds trop2 according to claim 1, wherein the antibody or antigen-binding fragment further comprises a heavy chain variable region having the amino acid sequence shown in SEQ ID No.7 and a light chain variable region having the amino acid sequence shown in SEQ ID No. 8.
  3. 3. An antibody or antigen-binding fragment that specifically binds trop2 according to claim 1 or 2, wherein the antibody or antigen-binding fragment further comprises a heavy chain constant region having the amino acid sequence shown in SEQ ID No.9 and a light chain constant region having the amino acid sequence shown in SEQ ID No. 10.
  4. 4. An antibody or antigen-binding fragment that specifically binds trop ' 2 according to claim 1, wherein the antibody or antigen-binding fragment is selected from the group consisting of monoclonal antibodies, chimeric antibodies, humanized antibodies, fab ', F (ab ') 2, fv, scFv and dsFv.
  5. 5. A nucleic acid molecule encoding the antibody or antigen binding fragment of any one of claims 1-4.
  6. 6.A recombinant vector comprising the nucleic acid molecule of claim 5.
  7. 7. A recombinant host cell comprising the nucleic acid molecule of claim 5 or the vector of claim 6.
  8. 8. A companion diagnostic kit for a humanized trop antibody-conjugated drug, comprising the antibody or antigen-binding fragment of any one of claims 1-4.
  9. 9. The use of the antibody or antigen binding fragment of any one of claims 1-4 in the preparation of a trop companion diagnostic immunohistochemical detection product matched with a breast cancer and pancreatic cancer targeted drug prior to treatment, wherein the targeted drug is a humanized trop2 antibody coupled drug.
  10. 10. A method for detecting trop's 2 expression for non-diagnostic purposes, characterized in that an isolated biological sample is detected using an antibody or antigen-binding fragment according to any one of claims 1 to 4, or a companion diagnostic kit according to claim 8.

Description

Antibody or antigen binding fragment specifically binding trop2 Technical Field The invention belongs to the technical field of biological detection, and particularly relates to an antibody or antigen binding fragment specifically binding trop < 2 >. Background Trop2, also known as tumor associated calcium channel sensing protein 2 (tumor-associated calcium signal transducer, TACSTD 2), is a cell surface glycoprotein, also known as an intracellular calcium signaling protein. Trop2 was first found in human placental trophoblasts and expressed in a variety of normal tissues. It was then found that various tumor cells had trop high expression. For example, trop2 is normally expressed predominantly in epithelial cells and plays a key role in embryonic development. Normal tissues such as skin, cornea, salivary gland, respiratory tract, lung and the like can detect trop expression, but the expression is limited. However trop is an important tumor promotion factor, has high expression in various malignant tumors, and common breast cancer, urothelial cancer, cervical cancer, pancreatic cancer and the like, so that trop2 is initiated as a target of tumor treatment. Antibody-conjugated drugs (ADCs) are a novel therapeutic means for delivering cytotoxic drugs by recognizing cancer cell target antigens using the specificity of monoclonal antibodies. The preparation method not only can realize accurate drug delivery and minimize toxicity of normal tissues, but also can expand treatment window and enhance pharmacokinetic and pharmacodynamic characteristics. In ADC, the antibody needs to have the characteristics of high specificity, low immunogenicity, long half-life, good stability and the like, and is a key factor for determining the curative effect of the medicine. Based on the above considerations, the present invention recognizes that the humanized trop antibody coupled with a therapeutic drug for breast cancer, urothelial cancer, cervical cancer and pancreatic cancer cells is premised on how to ensure specific recognition of tumor cells having trop2 membrane expression. In order to overcome the problem, the invention utilizes the antibody expression and screening technology, experiences immune response, antibody sorting, gene recombination, high-throughput expression and performance evaluation, screens trop antibody with highest sensitivity and strongest specificity, and uses the trop antibody in trop companion diagnostic kit antibody development of breast cancer and pancreatic cancer humanized trop2 antibody coupled cell therapeutic drugs. Disclosure of Invention In order to solve the defects in the prior art, the invention aims to provide an antibody or antigen binding fragment specifically binding trop, which is used for carrying out white rabbit immunization by taking trop protein constructed in vitro as an immunogen, and obtaining a hybridoma cell strain expressing the antibody through cell fusion and screening. In order to achieve the above object, the present invention adopts the following technical scheme: An antibody or antigen binding fragment that specifically binds trop2 comprising 3 CDRs in the heavy chain variable region amino acid sequence set forth in SEQ ID No.7 and 3 CDRs in the light chain variable region amino acid sequence set forth in SEQ ID No.8, or a variant having a single or multiple CDRs with the light heavy chain CDR regions of no more than 3 amino acid conservative changes per CDR region. Further, when encoding antibody HCDRs according to Kabat coding rules, the antibody or antigen-binding fragment includes heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, the HCDR1 amino acid sequence is shown as SEQ ID NO.1, the HCDR2 amino acid sequence is shown as SEQ ID NO.2, the HCDR3 amino acid sequence is shown as SEQ ID NO.3, the LCDR1 amino acid sequence is shown as SEQ ID NO.4, the LCDR2 amino acid sequence is shown as SEQ ID NO.5, the LCDR3 amino acid sequence is shown as SEQ ID NO.6, or variants having single or multiple CDRs from the 6 CDR regions of no more than 3 amino acid conservative changes per CDR region. Preferably, the aforementioned antibody or antigen binding fragment comprises a heavy chain variable region and a light chain variable region, the sequences being selected from the group consisting of: The heavy chain variable region has an amino acid sequence as shown in SEQ ID NO.7, or has at least 75%, 85%, 95% or 99% sequence identity to SEQ ID NO. 7; The amino acid sequence of the light chain variable region is shown as SEQ ID NO.8, or has at least 75%, 85%, 95% or 99% sequence identity to SEQ ID NO. 8. Preferably, the aforementioned antibody or antigen-binding fragment further comprises a heavy chain constant region having an amino acid sequence shown in SEQ ID NO.9 and a light chain constant region having an amino acid sequence shown in SEQ ID NO. 10. Preferably, the aforementi