Cambridge, Mass. — Immuto Scientific has unveiled new data showing that its structural surfaceomics platform identified previously unknown surface protein conformers associated with treatment resistance in non-small cell lung cancer.
The biotechnology company will present the findings at the inaugural AACR Drug Discovery and Development Conference. The research used patient-derived, EGFR-mutant lung adenocarcinoma models to examine structural changes on the surface of cells resistant to osimertinib, a targeted cancer therapy.
Immuto said its Rover structural surfaceomics platform identified candidate disease-specific surface protein conformers linked to the resistant state. The company is advancing therapeutic programs against targets identified through the research.
“Resistance to targeted therapy remains one of the most important challenges in non-small cell lung cancer, and new therapeutic targets are urgently needed,” said Faraz A. Choudhury, Ph.D., Co-Founder and Chief Executive Officer of Immuto Scientific. “These data show that structural surfaceomics can uncover disease-specific conformational targets that conventional genomics and proteomics miss. By identifying how surface proteins change shape in resistant disease states, we believe we can open new opportunities for ADCs, multispecifics, and other advanced biologics designed to more selectively target cancer cells.”
Many antibody-based therapies and antibody-drug conjugates used in non-small cell lung cancer target proteins that are overexpressed in tumors but are also found in normal epithelial tissues. This can contribute to on-target, off-tumor toxicity and restrict dosing.
Immuto’s platform is intended to identify targets based on disease-specific protein structures rather than relying solely on genetic mutations or protein abundance.
The study was conducted with Dr. Byoung Chul Cho, a medical oncologist, clinical trialist, and Professor at Yonsei University in Seoul, Korea, who specializes in lung cancer.
Researchers compared the structural surfaceomes of two patient-derived, EGFR-mutant cancer models, one sensitive to osimertinib and another resistant to the treatment. Using quantitative liquid chromatography-tandem mass spectrometry, the team measured changes in amino acid surface and solvent accessibility.
The analysis identified 19,020 modified peptides from 3,485 proteins. Of those, 2,518 peptides from 1,072 proteins showed significant changes in solvent accessibility. Researchers also identified several potential contributors to treatment resistance, including an epithelial-to-mesenchymal transition-like phenotype in the resistant cells.
“Resistance to EGFR-targeted therapy remains a major challenge for patients with non-small cell lung cancer, and new approaches are needed to identify therapeutic vulnerabilities that emerge in resistant disease,” said Dr. Cho. “These data suggest that structural changes on the cancer cell surface may provide an important and previously underexplored source of targets in treatment-resistant lung cancer. The ability to evaluate these changes in patient-derived models could open new opportunities for more selective therapeutic strategies.”
