Cell-Selective Targeting Chimeras (SelecTAC^B) for Membrane Protein Degradation on B Cells

Area of Science:

• Immunology
• Molecular Biology
• Biotechnology

Background:

• Targeted protein degradation technologies (TPDs) enable precise control over protein levels.
• Current TPDs lack cell-selectivity, especially for immune cell surface proteins.
• Degrading specific proteins on target immune cells is a significant challenge.

Purpose of the Study:

• To develop a cell-selective membrane protein degradation chimera (MPD) for B cells.
• To leverage CD22 as a B cell-specific receptor for targeted degradation.
• To establish a platform for selective protein degradation on immune cells.

Main Methods:

• Designed SelecTAC^B, a chimera utilizing CD22 for B cell targeting.
• Applied SelecTAC^B to human peripheral blood mononuclear cells (PBMCs).
• Assessed degradation of target proteins (CD40, ICOSL) on B cells.

Main Results:

• SelecTAC^B achieved targeted and cell-selective membrane protein degradation on B cells.
• Degradation occurred without affecting protein expression in other immune cell types.
• Inhibition of B cell functions was observed due to the degradation of key proteins.

Conclusions:

• SelecTAC^B is an effective B cell-selective degradation platform.
• This technology enables targeted membrane protein degradation on specific immune cells.
• Offers a general strategy for developing cell-type selective therapies for immune cells.