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Use of interferon in treatment of tumor, and related product and method

An interferon, tumor technology, applied in the field of tumor treatment

Active Publication Date: 2014-01-29
DINGFU BIOTARGET
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Indeed, although the potential cytotoxic effects of ADCs initially caused regressions, many patients experienced relapses or developed metastases

Method used

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  • Use of interferon in treatment of tumor, and related product and method
  • Use of interferon in treatment of tumor, and related product and method
  • Use of interferon in treatment of tumor, and related product and method

Examples

Experimental program
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Effect test

Embodiment 1

[0115] Type I interferons are required for effective tumor responses to antibody therapy in vivo

[0116] Type I interferons have been shown to serve as potentially critical danger signals in eliciting antitumor T cell responses in spontaneous tumor rejection and in various antitumor therapies. The current inventors hypothesized that anti-oncogenic receptor antibodies induce in tumor tissue Type I interferon production, which bridges innate and acquired immunity. To test whether tumor sensitivity to anti-oncogenic receptor antibodies correlates with post-treatment levels of type I interferon in the model described here, the inventors first generated two different tumor cell lines, antibody-responsive cells lines and antibody-resistant cell lines. TUBO mammary tumor cells were derived from Her2 / neu Tg mice, where Neu is the main signal for cell growth, and TUBO cells were used as anti-neu antibody responsive tumor cell lines. The EGFR-transfected B16 melanoma cell line, in wh...

Embodiment 2

[0118] Targeted delivery of interferon beta enhances antibody-mediated therapeutic efficacy

[0119] The data in Example 1 suggest that targeting type I interferons to tumors has potential immunotherapeutic effects, particularly for overcoming tumor resistance to antibody therapy. In order to further verify this conclusion and further improve the therapeutic effect, the current inventors prepared an anti-EGFR-interferon beta (Ab-IFN beta) fusion protein to deliver interferon beta directly to tumor tissues expressing EGFR in a targeted manner ( Figure 9 A). The present inventors first checked whether the anti-tumor function of anti-EGFR and interferon beta in this fusion protein remained intact. The inventors found that the fusion protein can bind EGFR + cell( Figure 9 B) And it can activate the type I interferon receptor signaling pathway (data not shown), so it can be seen that the anti-tumor functions of anti-EGFR and interferon β in the fusion protein are well maintain...

Embodiment 3

[0123] Therapeutic efficacy of an anti-EGFR-interferon beta fusion protein depends on acquired immunity

[0124] Type I interferons have multiple potential effects on tumor growth, including inhibition of proliferation, inhibition of angiogenesis, activation of innate immune cells, bridging innate and adaptive immunity, and direct activation of adaptive immune responses. To assess the relative contribution of acquired immunity among other anti-EGFR-IFNβ antitumor effects, B16-EGFR-bearing B6 Rag1 KO mice were treated with anti-EGFR-IFNβ. In contrast to the therapeutic effect observed in WT mice, similar doses of anti-EGFR-IFNβ failed to suppress tumors in these immunocompromised Rag1 KO mice ( image 3 A). Thus, these data support the conclusion that anti-EGFR-interferon beta mediated therapeutic effects largely require acquired immunity.

[0125] CD8 + T lymphocytes are the major cell population involved in controlling the growth of many tumors. To determine whether they ...

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Abstract

The invention relates to use of interferon in treatment of a tumor, and related products and a method, particularly relates to the field of tumor treatment, and especially aims at overcoming the resistance of the tumor on an antibody therapy. Particularly, the invention relates to application, and related product and method for inhibiting growth and recurrence of the tumor and causing tumor regression by combined utilization of interferon, especially I-type interferon, and a compound for blocking up a programmed death 1 or programmed death ligand (PD-1 / PDL) passage.

Description

technical field [0001] The invention relates to the field of tumor therapy, in particular to overcoming tumor resistance to antibody therapy. Specifically, the present invention relates to blocking PD-1 (programmed death-1) / PDL (programmed death ligand, PD-1 Ligand) pathway by interferon, such as type I interferon and its The combination of the compounds inhibits tumor growth and recurrence and causes tumor regression. Background technique [0002] It is currently accepted that antibodies targeting oncogenic receptors, such as cetuximab and Herceptin, have antitumor effects because of their ability to block growth signaling induction, cell cycle arrest, and / or through apoptosis or antibody-dependent cell-mediated cytotoxicity (ADCC) to induce cell death. However, most studies on antibody-mediated antitumor mechanisms are based on human tumor experiments from in vitro culture or in vivo xenograft models, which do not include the contribution of adaptive immune responses. M...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P35/00A61K38/21
Inventor 杨选明傅阳心
Owner DINGFU BIOTARGET
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