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Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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Enhancing NK Cell Activity in Colorectal Cancer with an Fc-Optimized Antibody Targeting CD276 (B7-H3).

Sylwia A Stefańczyk1,2,3, Xenija Kaiser1,2,3, Ilona Hagelstein1,2,3

  • 1Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital of Tübingen, Tübingen, Germany.

Immunotargets and Therapy
|February 19, 2026
PubMed
Summary

An Fc-optimized anti-CD276 antibody (8H8_SDIE) enhances natural killer (NK) cell activity against colorectal cancer (CRC) cells in vitro. This novel immunotherapy shows promise for treating microsatellite-stable CRC, warranting further investigation.

Keywords:
ADCCB7-H3Fc engineeringbench to bedsidecolon cancerimmunotherapy

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Colorectal cancer (CRC) poses a significant global health challenge, especially in advanced stages with limited treatment options.
  • Current immunotherapies like PD-1/PD-L1 inhibitors are effective mainly for microsatellite instability-high (MSI-H) CRC.
  • CD276 (B7-H3) is an immune checkpoint molecule overexpressed in CRC, presenting a potential therapeutic target.

Purpose of the Study:

  • To evaluate an Fc-optimized anti-CD276 monoclonal antibody (8H8_SDIE) for its ability to enhance natural killer (NK) cell activity in colorectal cancer.
  • To assess the binding specificity and NK cell activation potential of 8H8_SDIE against CD276-positive CRC cells.

Main Methods:

  • Development of an Fc-optimized anti-CD276 antibody (8H8_SDIE) designed to improve CD16 binding.
  • In vitro experiments using human CRC cell lines and healthy donor peripheral blood mononuclear cells (PBMCs).
  • Assessment of NK cell activation markers, cytotoxic mediators, and tumor cell lysis induced by 8H8_SDIE.

Main Results:

  • 8H8_SDIE demonstrated specific binding to CD276-expressing CRC cells.
  • Significant enhancement of NK cell activation, including increased expression of activation markers and secretion of cytotoxic mediators.
  • Potent NK cell-mediated lysis of colorectal cancer cells was observed in vitro.

Conclusions:

  • The Fc-optimized anti-CD276 antibody 8H8_SDIE effectively boosts NK cell reactivity against CD276-positive CRC cells.
  • 8H8_SDIE shows potential as a novel immunotherapeutic agent for colorectal cancer, particularly for microsatellite-stable disease.
  • Further preclinical and clinical studies are warranted to explore the therapeutic potential of 8H8_SDIE in CRC treatment.