light-anti-tumor antigen antibodies for the prevention and treatment of primary and metastatic cancers

A technology for antibodies and tumors, which can be used in antitumor drugs, chemical instruments and methods, medical preparations containing active ingredients, etc., and can solve problems such as heart side effects

Active Publication Date: 2018-12-04
SUZHOU DINGFU BIOTARGET CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, long-term (52 ​​weeks) use concomitant with paclitaxel immunization often resulted in cardiac side effects

Method used

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  • light-anti-tumor antigen antibodies for the prevention and treatment of primary and metastatic cancers
  • light-anti-tumor antigen antibodies for the prevention and treatment of primary and metastatic cancers
  • light-anti-tumor antigen antibodies for the prevention and treatment of primary and metastatic cancers

Examples

Experimental program
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Effect test

Embodiment 1

[0199] Example 1: Coupling or conjugation of LIGHT expression to a tumor targeting agent

[0200] 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

[0201] Example 2: Adv-LIGHT can promote the rejection of Her2+ tumors

[0202] LIGHT-expressing adenovirus was locally delivered to Her2+ tumors to test whether local administration of LIGHT could promote the rejection of Her2+ tumors.

[0203] 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.

[0204] 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 the mouse mutant LIGHT, the mutant LIGHT is LIGHT resistant to protease degradation; the construction process of adv-lacz and adv-mmlit are shown in...

Embodiment 3

[0205] Example 3: Functional activity of LIGHT-antibody fusion protein

[0206] 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 connected with a LIGHT protein or a LIGHT protein fragment, a composition containing the antibody, a method for preventing and treating cancers, and application to prevention and treatment of cancers. The LIGTH-antibody and the composition provided by the invention can be used for preventing or treating primary tumors and / or metastatic tumors, and reducing, inhibiting and lowering the growth of primary tumors and / or cancer metastasis.

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application number 200910136143.4, the application date is May 4, 2009, and the invention title is "LIGHT-anti-tumor antigen antibody for the prevention and treatment of primary and metastatic cancer". technical field [0002] 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 [0003] LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator A receptor expressed by T lymphocytes)) is a re...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/19A61K47/42A61P35/00A61P35/04
Inventor 傅阳心
Owner SUZHOU DINGFU BIOTARGET CO LTD
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