Pharmaceutical composition for treatment and/or prevention of cancer

A technology for drugs and serial numbers, which can be used in drug combination, drug delivery, medical preparations containing active ingredients, etc., and can solve the problems of weakened anti-tumor effect of imiquimod

Pending Publication Date: 2020-11-13
TORAY IND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, it has been reported that rituximab (a monoclonal antibody that specifically binds to the CD20 protein expressed on the surface of cancer cells) has been administered as a cancer antibody drug for the treatment of non-Hodgkin's lymphoma. ) case of basal cell carcinoma that occurred in a patient with experience of imiquimod, a case where the antitumor effect of imiquimod was weakened (Non-Patent Document 4)

Method used

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  • Pharmaceutical composition for treatment and/or prevention of cancer
  • Pharmaceutical composition for treatment and/or prevention of cancer
  • Pharmaceutical composition for treatment and/or prevention of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0195] Example 1 Preparation of Anti-CAPRIN-1 Antibody

[0196] In the present invention, an anti-CAPRIN-1 antibody immunoreactive with CAPRIN-1 protein was used, and the antibody prepared as follows was used.

[0197] (polyclonal antibody)

[0198] Mix 1 mg of human CAPRIN-1 recombinant protein prepared according to Example 3 of WO2010 / 016526 with an equal volume of incomplete Fluorine's adjuvant (IFA) solution, and administer it subcutaneously to rabbits every 2 weeks. with 4 times. Blood is then collected to obtain antiserum containing polyclonal antibodies. This antiserum was further purified using a protein G carrier (manufactured by GE Helus Kea Biosciences Co., Ltd.) and replaced with PBS (-) to obtain a polyclonal antibody against the CAPRIN-1 protein (anti-CAPRIN-1 polyclonal antibody #1).

[0199] (Monoclonal antibodies)

[0200] 100 μg of human CAPRIN-1 recombinant protein prepared according to Example 3 of WO2010 / 016526 was mixed with an equal amount of MPL+TDM...

Embodiment 2

[0207] Example 2 The anti-tumor effect produced by the combined use of anti-CAPRIN-1 antibody and imiquimod

[0208] Next, the anti-CAPRIN-1 antibody prepared in Example 1 (anti-CAPRIN-1 polyclonal antibody #1 and humanized antibody #1) was administered in combination with imiquimod to produce tumor-bearing mice. The antitumor effect was evaluated.

[0209] Specifically, using NOD-SCID mice obtained by subcutaneously transplanting human-derived cancer cells expressing CAPRIN-1 protein, the anti-tumor effect produced by the combined use of anti-CAPRIN-1 antibody and imiquimod in the present invention was studied. Effect. For each mouse, 10 7 Human breast cancer cells BT474 were mixed with Matrigel (SIGMA) and transplanted subcutaneously to grow to a tumor size of about 60mm 3 , so as to produce cancer-bearing mice. BT474 expresses CAPRIN-1 protein on the cell membrane surface, and it was confirmed that the anti-CAPRIN-1 antibody produced in Example 1 reacts with a part of C...

Embodiment 3

[0214] Example 3 Comparison with antitumor effect produced by combined use of anti-CAPRIN-1 antibody and anticancer agent

[0215] Next, the combination of the anti-CAPRIN-1 antibody prepared in Example 1 (anti-CAPRIN-1 polyclonal antibody #1 and humanized antibody #1) and imiquimod was administered to the generated cancer-bearing mouse organisms. The antitumor effect was compared with the tumor effect when the above-mentioned antibody was used in combination with a conventional anticancer agent other than imiquimod.

[0216] Specifically, using NOD-SCID mice obtained by subcutaneously transplanting human-derived cancer cells expressing CAPRIN-1 protein, the anti-tumor effect produced by the combined use of anti-CAPRIN-1 antibody and imiquimod in the present invention was studied. Effect. For each mouse, 10 7 Human breast cancer cell line BT474 is mixed with Matrigel (Matrigel) (SIGMA) to inhibit it subcutaneously, allowing it to grow to a tumor size of about 90mm 3 , so as...

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Abstract

The present invention provides a pharmaceutical product for treatment and / or prevention of cancer, characterized by including imiquimod together or separately in combination with an antibody, or a fragment thereof, having immunological reactivity with a CAPRIN-1 protein. With this pharmaceutical product, it is possible to treat and / or prevent cancer that specifically expresses the CAPRIN-1 proteinon a cell surface.

Description

technical field [0001] The present invention relates to a medicine for treating and / or preventing cancer using an antibody against CAPRIN-1 protein or a fragment thereof and imiquimod. Background technique [0002] Various antibody drugs targeting specific antigenic proteins on cancer cells are used in cancer therapy as cancer therapeutic drugs with few side effects due to their cancer specificity. For example, the cell membrane surface of various solid cancers expresses cytoplasmic proliferation-associated protein 1 (Cytoplasmic-activation and proliferation-associated protein 1, CAPRIN-1). Use in medicine (Patent Document 1). [0003] In recent years, in order to enhance the effectiveness of cancer therapeutic drugs, a combination of multiple cancer therapeutic drugs has been used clinically as a standard therapy. For example, combinations of irinotecan, folinic acid, and 5-fluorouracil for colorectal cancer, doxorubicin and cyclophosphamide for breast cancer, or paclitax...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K31/4745A61P35/00A61P35/02A61P43/00C07K16/30C07K16/46C12N15/13
CPCA61K31/4745A61P35/00C07K16/28C07K2317/24A61K2039/505A61K39/39541A61K2039/545A61K2039/54A61K2300/00A61K39/395A61K9/0014C07K16/30C07K16/46A61P35/02A61K31/337A61K31/437A61K39/3955
Inventor 冈野文义斋藤孝则
Owner TORAY IND INC
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