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CTLA-4 Antibody Pharmacological Models

2017-05-25 16:07:33.0

Basic characteristics:

CTLA-4 gene function:

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152, plays an important regulatory role in T cell activation. Cytotoxic T lymphocyte related proteins expressed on the cell surface can competitively inhibit the binding of B7 to CD28 on the surface of the T cell when it binds to (B7-1 CD80) and B7-2 (CD86) on the surface of antigen-presenting cells (APCs), thus inhibiting the T cell activation process. The inhibition of CTLA-4 by inhibitory antibodies can block this mechanism, thereby enhancing T cell activity. CTLA-4 is the first immunological target of clinical concern, and plays an important role in the negative regulation of immune response. The CTLA-4 antibody is also the first FDA-approved antibody to treat advanced melanoma.

Targeting strategy

Targeted allele:

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mRNA expression verification:

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Fig 1. Molecular identification of B-hCTLA-4 humanized mice. mCTLA-4 mRNA expression was detected in spleen cells of B-hCTLA-4 heterozygous mice.


Protein expression verification:

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Fig 2. B-hCTLA-4 humanized mice spleen cell activation and flow cytometry.

mCTLA-4+ cells were detected in C57BL/6 mice. hCTLA-4+ cells were detected in B-hCTLA-4 homozygous mice.


CTLA-4 antibody efficacy validation:

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Fig 3. B-hCTLA-4 mice were used for hCTLA-4 antibody efficacy validation. Mouse colon cancer MC38 cells were subcutaneously transplanted into B-hCTLA-4 homozygous mice, and animals were grouped into control to treatment groups (n=5) when the tumor size is approximately 100 mm3. Anti-hCTLA-4 antibody Yervoy shows substantially inhibitory effects at 3 different doses. The average±SEM of tumor sizes are shown in the figure. B-hCTLA-4 mice are effective tools for hCTLA-4 antibody efficacy validation.


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