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Related Experiment Video

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Analysis of aDR5scFv with Specific Identification and Function.

Xiaofeng Cheng1,2, Qingyu Meng2, Chunling Gao1

  • 11 Radiotherapy Department, ChengGong Hospital, Xiamen University , Xiamen, Fujian, China .

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
|February 13, 2016
PubMed
Summary
This summary is machine-generated.

Engineered antibody fragments targeting Death Receptor 5 (DR5) offer a promising cancer therapy. A novel anti-DR5 single-chain variable fragment (aDR5scFv) selectively induced apoptosis in lung cancer cells and inhibited tumor growth in vivo.

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Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Recombinant soluble TRAIL and anti-DR5 monoclonal antibodies show potential for cancer therapy by inducing cell death via Death Receptor 5 (DR5).
  • However, these agents can cause apoptosis in normal cells, particularly hepatocytes, limiting their clinical application.
  • Engineered antibody fragments, such as single-chain variable fragments (scFv), are emerging as therapeutic candidates due to high affinity, specificity, and reduced immunogenicity.

Purpose of the Study:

  • To construct and express a novel anti-DR5 single-chain variable fragment (aDR5scFv).
  • To evaluate the therapeutic efficacy of aDR5scFv against human lung adenocarcinoma cells (973) in vitro and in vivo.
  • To assess the potential of aDR5scFv as a novel cancer therapeutic agent.

Main Methods:

  • Construction and expression of aDR5scFv targeting human DR5 (eDR5).
  • In vitro assessment using MTT assay and flow cytometry to detect apoptosis in 973 cells.
  • In vivo evaluation in mice using hematoxylin and eosin staining and TUNEL assay to assess tumor growth inhibition and apoptosis, in combination with radiotherapy.

Main Results:

  • The constructed aDR5scFv specifically recognized and bound to eDR5.
  • aDR5scFv effectively induced apoptosis in 973 lung adenocarcinoma cells in vitro.
  • In vivo studies demonstrated that aDR5scFv inhibited tumor growth in mice, with comparable effects to radiotherapy, and increased expression of apoptosis-related proteins like caspase-3, Bax, and cytochrome c.

Conclusions:

  • The engineered aDR5scFv exhibits specific binding to eDR5 and potent anti-tumor activity.
  • aDR5scFv demonstrates the ability to induce apoptosis in lung cancer cells both in vitro and in vivo.
  • This novel aDR5scFv represents a potential new therapeutic candidate for cancer treatment, possibly in combination therapies.