阅读说明：本技术 一种用于癌症治疗的免疫检查点抑制剂 (Immune checkpoint inhibitor for cancer treatment ) 是由 蒋可 于 2020-05-27 设计创作，主要内容包括：本发明保护一种用于癌症治疗的免疫检查点抑制剂,特别地,本发明提供一种单克隆抗体,所述单克隆抗体为一种人源化单克隆抗体,其能够特异性地与ILDR2结合,并且能够十分有效地抑制其ILDR2免疫作用,具备抑制肿瘤进程的功能。(The present invention protects an immune checkpoint inhibitor for cancer therapy, and particularly provides a monoclonal antibody, which is a humanized monoclonal antibody, can specifically bind to ILDR2, can effectively inhibit ILDR2 immunization, and has a tumor progression inhibiting function.)

1.An immune checkpoint inhibitor for use in the treatment of cancer, wherein the immune checkpoint inhibitor is an antibody targeting human ILDR 2.

2. The immune checkpoint inhibitor of claim 1 wherein the functional polypeptide fragment comprises a light chain and a heavy chain; the light chain comprises CDR-L1, CDR-L2 and CDR-L3, and the amino acid sequence of CDR-L1 is shown as SEQ ID NO. 1; the amino acid sequence of CDR-L2 is shown as SEQ ID NO. 2, and the amino acid sequence of CDR-L3 is shown as SEQ ID NO. 3; the heavy chain comprises CDR-H1, CDR-H2 and CDR-H3, wherein the amino acid sequence of CDR-H1 is shown as SEQ ID NO. 4, the amino acid sequence of CDR-H2 is shown as SEQ ID NO. 5, and the amino acid sequence of CDR-H3 is shown as SEQ ID NO. 6.

3. The immune checkpoint inhibitor as claimed in claim 1 wherein the antibody and functional fragments thereof are anti-human ILDR2 chimeric antibodies and/or active fragments thereof.

4. The immune checkpoint inhibitor as claimed in claim 1 wherein the antibody and functional fragments thereof are anti-human ILDR2 humanized antibodies and/or active fragments thereof.

5. The immune checkpoint inhibitor as claimed in claim 1 wherein the antibody heavy chain variable region amino acid sequence is shown as SEQ ID No. 7 and the antibody light chain variable region amino acid sequence is shown as SEQ ID No. 8.

6. The immune checkpoint inhibitor as claimed in claim 1 wherein the antibody heavy chain variable region amino acid sequence is shown as SEQ ID No. 11 and the antibody light chain variable region amino acid sequence is shown as SEQ ID No. 15.

7. The immune checkpoint inhibitor of claim 1 wherein the antibody comprises an amino acid sequence at either Fc terminus selected from the group consisting of human antibodies IgG1, IgG2, IgG3, IgG 4.

8. The immune checkpoint inhibitor according to claim 1 wherein the step of producing the immune checkpoint inhibitor comprises: culturing a host cell comprising the antibody of claim 6 or claim 7 in a culture medium and under suitable culture conditions; recovering the produced antibody and active fragments thereof from the culture medium or from the cultured host cells and formulating with a pharmaceutically acceptable carrier into an immune checkpoint inhibitor.

9. The immune checkpoint inhibitor as claimed in claim 1 wherein the immune checkpoint inhibitor may inhibit the progression of cancer including but not limited to leukemia, lymphoma, myeloma, brain tumor, head and neck squamous cell carcinoma, non-small cell lung cancer, nasopharyngeal carcinoma, esophageal cancer, gastric cancer, pancreatic cancer, gallbladder cancer, liver cancer, colorectal cancer, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, bladder cancer, renal cell carcinoma, melanoma.

Technical Field

The present invention relates to the field of immune checkpoint inhibitors, in particular to an immune checkpoint inhibitor for cancer therapy.

Background

Mabs targeting co-inhibitory immune checkpoints, such as PD-1 and CTLA-4, have shown clinical activity in a variety of malignancies, including melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer, head and neck squamous cell carcinoma, MSI high colorectal cancer, Merkel cell carcinoma and hodgkin lymphoma, and have altered medical oncology practices.

In particular, immune checkpoint inhibitors have been successful in melanin therapy, with approved treatment regimens including anti-PD-1 (nivolumab and pembrolizumab), anti-CTLA-4 (ipilimumab) and anti-PD-1/CTLA-4 combination (nivolumab-ipilimumab).

At present, the experience of experts on the treatment of various malignant tumors by using the immune checkpoint inhibitor is more and more abundant, and more tumor diseases are brought into the scope of immunotherapy. Meanwhile, medical experts continuously explore the combined application mode of other tumor treatment modes and immunotherapy, and strive to further improve the treatment effect of malignant tumors. However, although immune checkpoint inhibitors may temporarily reactivate CTLs, enhancing tumor control, if effector memory T cells are damaged, the clinical response may subside, causing tumor recurrence after acquired resistance or withdrawal.

In order to solve the technical problems, the invention provides a brand-new immune checkpoint inhibitor for cancer treatment, which can be used for high-efficiency adjuvant treatment of various solid tumors and non-solid tumors without side effects so as to achieve the purposes of relieving pain, slowing disease course and/or curing.

Disclosure of Invention

In order to solve the above technical problems, the present invention provides an immune checkpoint inhibitor for cancer treatment.

The invention is realized by the following technical scheme:

an immune checkpoint inhibitor for use in the treatment of cancer, which immune checkpoint inhibitor is an antibody targeting human ILDR 2.

Further, the functional fragment of the polypeptide comprises a light chain and a heavy chain; the light chain comprises CDR-L1, CDR-L2 and CDR-L3, and the amino acid sequence of CDR-L1 is shown as SEQ ID NO. 1; the amino acid sequence of CDR-L2 is shown as SEQ ID NO. 2, and the amino acid sequence of CDR-L3 is shown as SEQ ID NO. 3; the heavy chain comprises CDR-H1, CDR-H2 and CDR-H3, wherein the amino acid sequence of CDR-H1 is shown as SEQ ID NO. 4, the amino acid sequence of CDR-H2 is shown as SEQ ID NO. 5, and the amino acid sequence of CDR-H3 is shown as SEQ ID NO. 6.

Further, the antibody and the functional fragment thereof are anti-human ILDR2 chimeric antibody and/or an active fragment thereof.

Further, the antibody and the functional fragment thereof are anti-human ILDR2 humanized antibodies and/or active fragments thereof.

Furthermore, the amino acid sequence of the heavy chain variable region of the antibody is shown as SEQ ID NO. 7, and the amino acid sequence of the light chain variable region of the antibody is shown as SEQ ID NO. 8.

Furthermore, the amino acid sequence of the heavy chain variable region of the antibody is shown as SEQ ID NO. 11, and the amino acid sequence of the light chain variable region of the antibody is shown as SEQ ID NO. 15.

Further, the antibody comprises an amino acid sequence of any Fc-terminus selected from the group consisting of human antibodies IgG1, IgG2, IgG3, IgG 4.

Further, the step of producing the immune checkpoint inhibitor comprises: culturing a host cell containing the above antibody in a medium and under suitable culture conditions; recovering the produced antibody and active fragments thereof from the culture medium or from the cultured host cells and formulating with a pharmaceutically acceptable carrier into an immune checkpoint inhibitor.

Further, the immune checkpoint inhibitor may inhibit the progression of cancer including, but not limited to, leukemia, lymphoma, myeloma, brain tumor, head and neck squamous cell carcinoma, non-small cell lung cancer, nasopharyngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, gallbladder cancer, liver cancer, colorectal cancer, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, bladder cancer, renal cell carcinoma, melanoma.

It is well known in the art that an antigen binding domain refers to a region that can specifically interact with a target molecule, such as an antigen, with a high degree of selectivity of action, and that sequences recognizing one target molecule are generally unable to recognize other molecular sequences.

Representative antigen binding domains include: a variable region of an antibody, a structural variant of a variable region of an antibody, a binding domain of a receptor, a ligand binding domain, or an enzyme binding domain.

IgG is an abbreviation of Immunoglobulin G (IgG), which is a major antibody component of serum, and human IgG has four subtypes based on the r-chain antigenic difference in IgG molecules: IgG1, IgG2, IgG3, IgG 4.

The binding specificity and avidity of an antibody are determined primarily by the CDR sequences, and variants with similar biological activity can be obtained by readily altering the amino acid sequence of the non-CDR regions according to well-established and well-known techniques of the art.

Host cells of the invention include, but are not limited to, E.coli, phage display systems, yeast, plant cells, animal cells.

Pharmaceutically acceptable carriers refer to immune checkpoint inhibitor carriers that are conventional in the pharmaceutical art, including but not limited to diluents, excipients, water, and the like; including but not limited to adhesives such as gelatin and polyvinylpyrrolidone; humectants such as glycerol; including but not limited to absorption enhancers such as quaternary ammonium compounds; including but not limited to surfactants such as cetyl alcohol, sodium lauryl sulfate, and the like.

The monoclonal antibody, particularly RCA-2933, can be well specifically combined with ILDR2, can effectively inhibit ILDR2 immunity, and has the functions of inhibiting cancer progression of leukemia, lymphoma, myeloma, brain tumor, head and neck squamous cell carcinoma, non-small cell lung cancer, nasopharyngeal carcinoma, esophageal cancer, gastric cancer, pancreatic cancer, gallbladder cancer, liver cancer, colorectal cancer, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, bladder cancer, renal cell carcinoma and melanoma.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail below.