Lymphocyte display: a novel antibody selection platform based on T cell activation

Area of Science:

• Immunotechnology
• Biotechnology
• Antibody Engineering

Background:

• Current antibody display platforms require modifications for human use and are limited to accessible antigens.
• Existing platforms are not suitable for in vivo selections, hindering broader applications.

Purpose of the Study:

• To develop a novel cell-based antibody display platform utilizing T lymphocytes.
• To link antigen-antibody interactions to T cell activation for antibody selection.

Main Methods:

• Engineered T lymphocytes to express chimeric-immune receptors (CIRs) displaying antibodies on their surface.
• Utilized T cell activation marker CD69 expression as a readout for antigen binding.
• Performed in vitro selection against tumor cells expressing carcinoembryonic antigen using FACS sorting of CD69(+) T cells.

Main Results:

• Demonstrated successful isolation of tumor-specific antibody binders.
• Achieved an enrichment factor of at least 10(3)-fold after two rounds of selection.
• Obtained a homogeneous population of T cells expressing tumor-specific CIRs.

Conclusions:

• The novel T lymphocyte-based platform enables efficient selection of antibodies against cell surface antigens.
• This approach links antibody-antigen recognition to T cell activation, facilitating antibody discovery.
• The platform shows promise for developing targeted immunotherapies and diagnostic tools.