New Imaging Technique Reveals How Antibodies Reshape Cancer Cell Receptors

Therapeutic antibodies person transformed crab treatment, yet nan nonstop molecular mechanisms that thrust their therapeutic effects person remained elusive. A squad led by Ralf Jungmann (Chair Professor for Molecular Physics of Life astatine LMU and leader of nan Molecular Imaging and Bionanotechnology investigation group astatine nan Max Planck Institute of Biochemistry) has now taken an unprecedented look astatine really therapeutic antibodies reshape receptor statement astatine nan single-molecule level, and really this affects nan usability of nan antibodies.

Using Resolution Enhancement by Sequential Imaging (RESI) - a caller super-resolution microscopy method tin of visualizing azygous proteins - nan researchers straight imaged nan nanoscale architecture of CD20 receptors and their interactions pinch wide utilized anti-CD20 antibodies specified arsenic Rituximab and Obinutuzumab.

"For nan first time, we tin visualize successful intact cells really antibody-receptor complexes shape astatine nan single-protein level," explains Ralf Jungmann, elder writer of nan study, which was published precocious successful nan diary Nature Communications. "These nanoscale patterns straight correlate pinch therapeutic usability and supply a blueprint for logical antibody design."

Therapeutic monoclonal antibodies enactment done aggregate mechanisms - triggering immune cells, activating complement pathways, aliases straight inducing compartment death. These effects dangle connected really antibodies hindrance and reorganize receptors connected nan compartment surface. However, accepted imaging methods lacked nan solution to uncover these arrangements successful their autochthonal cellular context.

The Jungmann squad overcame this obstruction by implementing multi-target 3D RESI imaging, a method that labels receptors and antibodies pinch orthogonal DNA barcodes and sequentially visualizes them astatine sub-nanometer precision. This allowed nan squad to resoluteness nan statement of CD20 receptors and their bound antibodies straight connected nan compartment membrane.

Beyond CD20, this RESI exertion is tin of investigating virtually immoderate membrane receptor and therapeutic antibody pinch molecular solution straight astatine intact cells. Because RESI visualizes full cells pinch precocious throughput, it enables systematic study of antibody candidates astatine a solution antecedently only accessible done cryo-EM, but now straight successful nan cellular situation and pinch unsocial molecular specificity.

Looking ahead, nan squad envisions combining RESI pinch nan imaging of aggregate receptors and intracellular signaling molecules to representation full therapeutic pathways. "For nan first time, RESI combines nan building of nanoscale receptors pinch their usability successful a cellular context," summarizes Jungmann. "This exertion has nan imaginable to fundamentally toggle shape immunotherapies."

Source:

Journal reference:

Pachmayr, I., et al. (2025) Resolving nan structural ground of therapeutic antibody usability successful crab immunotherapy pinch RESI. Nature Communications. doi.org/10.1038/s41467-025-61893-w.