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A rapid in vitro methodology for simultaneous target discovery and antibody generation against functional cell

Allison M L Nixon1,2, Alejandro Duque1, Nicholas Yelle3,4

  • 1Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.

Scientific Reports
|January 31, 2019
PubMed

Insights

Researchers developed a novel in vitro method for discovering cell surface targets and generating human antibodies simultaneously. This technique successfully identified new targets on colorectal cancer-initiating cells (CICs), enabling their isolation and potential therapeutic strategies.

Area of Science:

  • Biomedical Research
  • Immunology
  • Oncology

Background:

  • Cell surface antigen discovery is crucial for isolating rare cells and developing targeted therapies.
  • Existing methods for antibody generation can be time-consuming and costly.

Purpose of the Study:

  • To develop a rapid, cost-effective, in vitro technology for simultaneous cell surface target discovery and human antibody generation.
  • To apply this technology to human colorectal cancer-initiating cells (CICs) and identify novel therapeutic targets.

Main Methods:

  • A novel in vitro technology was employed for simultaneous target discovery and antibody generation.
  • The technique was applied to human colorectal cancer-initiating cells (CICs).
  • Antibody candidates were characterized, and their protein targets were identified.

Main Results:

  • Hundreds of unique human antibodies were identified against colorectal CICs.
  • Top antibody candidates targeted integrin α7 (ITGA7), HLA-A1, and integrin β6 (ITGB6).
  • The ITGA7 antibody successfully isolated colorectal CICs and identified glioblastoma and muscle stem cells; ITGB6 ablation impaired CIC function.

Conclusions:

  • The developed methodology enables rapid identification of novel cell surface targets and generation of specific antibodies.
  • This approach has broad applicability for stem cells, cancer cells, and immune cells, facilitating therapeutic development.
  • The identified targets (ITGA7, HLA-A1, ITGB6) offer potential for isolating and targeting specific cell populations, including cancer-initiating cells.

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