LIGHT-antitumor-antigen antibody for preventing and treating primary and metastatic cancer

An antibody and tumor technology, applied in anti-tumor drugs, gene therapy, biochemical equipment and methods, etc., can solve problems such as cardiac side effects

Inactive Publication Date: 2010-09-08
傅阳心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, long-term (52 ​​weeks) use concomitant with pacl

Method used

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  • LIGHT-antitumor-antigen antibody for preventing and treating primary and metastatic cancer
  • LIGHT-antitumor-antigen antibody for preventing and treating primary and metastatic cancer
  • LIGHT-antitumor-antigen antibody for preventing and treating primary and metastatic cancer

Examples

Experimental program
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Effect test

Embodiment 1

[0150] Example 1: Coupling or conjugation of LIGHT expression to a tumor targeting agent

[0151] In one aspect, to enable delivery of a mutant LIGHT expressing delivery system or an equivalent delivery system, the mutant LIGHT can be coupled or conjugated to a tumor targeting agent such as a tumor specific antibody. For example, tumor-specific antibodies can be conjugated to LIGHT, thereby selectively delivering the fusion protein to tumor sites. In addition, tumor-specific antibodies can be engineered to be expressed on the surface of viral delivery systems, or liposomal vesicles can be coated with tumor-specific antibodies. A delivery vehicle expressing mutated LIGHT and containing a tumor-targeting agent will first target specific tumor cells, and then transform the tumor cells to express mutated LIGHT on the surface of the tumor cells. This targeted expression of mutant LIGHT on the tumor surface will induce chemokines on stromal cells surrounding the tumor to attract T ...

Embodiment 2

[0152] Example 2: Adv-LIGHT can promote the rejection of Her2+ tumors

[0153] LIGHT-expressing adenovirus was locally delivered to Her2+ tumors to test whether local administration of LIGHT could promote the rejection of Her2+ tumors.

[0154] figure 2 These results demonstrate that delivery of LIGHT to neu+ tumors can enhance anti-neu immunity. Adv-mmlit (adenovirus expressing murine mutant LIGHT) inhibits neu+N202 tumor growth, even in Her2 transgenic mice.

[0155] Transgenic FBV mice expressing Her2 develop mammary tumors in adulthood that resemble human breast cancer and are extremely difficult to treat because of the preexisting Her2 expression in the transgenic mice and resistance to Her2 may have developed. On days 18 and 20 approximately 2 x 10 10 The adv-lacz or adv-mmlit of the virus particle (adenovirus expressing mouse mutant LIGHT, the mutant LIGHT is LIGHT resistant to protease degradation; the construction process of adv-lacz and adv-mmlit see The Journal of...

Embodiment 3

[0156] Example 3: Functional activity of LIGHT-antibody fusion proteins

[0157] By flow cytometry, LTβR-Ig and HVEM-Ig were used to measure the binding ability of 237-LIGHT (a fusion protein of 237 antibody and LIGHT, see Materials and Methods for its construction) to the receptor of LIGHT (LTβR and HVEM) ( image 3 ). image 3 It was shown that this fusion protein can still maintain the ability to bind to tumors and LIGHT receptors. The fusion protein can bind LTβR and HVEM after binding to tumor (237 specifically binds to Ag104). To test whether this fusion protein still retains its ability to activate T cells, we first tested 237-LIGHT in vitro for its ability to co-stimulate T cells in the presence of a suboptimal dose of plate-bound anti-CD3, thereby determining its functional activity . The results showed that the functionality of 237-LIGHT was comparable to that of anti-CD28 (see Figure 4 ). Therefore, it was shown that our strategy for generating fusion proteins...

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Abstract

The invention relates to a tumor specific antibody linked with LIGHT protein or fragments thereof, a combination comprising the same, a method for preventing and treating cancer and application thereof. The LIGHT-antibody and combination of the invention are applicable to preventing and treating primary and/or metastatic cancer and reducing, inhibiting and decreasing primary tumor growth and/or cancer metastasis.

Description

technical field [0001] The present invention belongs to the field of cancer prevention and treatment. The present invention relates to a tumor-specific antibody linked to LIGHT protein or its fragment, a composition containing the antibody, a method and application for preventing and treating cancer. Background technique [0002] LIGHT (homologous to l ymphotoxin, exhibits i nducible expression, and competes with HSV g lycoprotein D for h erpes virus entry mediator, areceptor expressed by T lymphocytes (homologous to lymphotoxin, exhibit inducible expression, and compete with HSV glycoprotein D for the herpesvirus entry mediator—a receptor expressed by T lymphocytes)) are recently identified TNF ligand superfamily type II transmembrane glycoprotein. LIGHT (TNFSF 14) is a member of the tumor necrosis factor (TNF) family, which interacts with lymphotoxin β receptor (LTβR, Lymphotoxin β receptor) and herpes virus entry mediator (HVEM, herpes virus) mainly expressed on st...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K38/17A61K31/7088A61K48/00A61P35/00A61P35/04C12N15/62C12N15/63C12N1/00C12N5/10A61K47/42A61K47/64
Inventor 傅阳心
Owner 傅阳心
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