Optimizing Differential Ion Mobility-Mass Spectrometry based Leukemia Antigen Detection

Undergraduates: Ian Schlup, Courtney Elliot James Keating, Sally Hunsucker Paul Armistead, Gary Glish

Faculty Advisor: Gary Glish
Department: Chemistry

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T cell-based therapies offer a promising means of treating leukemia more selectively than commonly used radiation and chemotherapies. The efficient development of these therapies requires the ability to confirm the presence of immunogenic antigens in patient samples. The amino acid sequences of leukemia peptide antigens can be computationally predicted, but development of therapies for the huge number of computationally predicted peptides is unrealistic. Detection of these peptides in tumor cells would provide targets that could be realistically targeted for therapeutic development. Differential ion mobility spectrometry (DIMS) coupled to mass spectrometry provides a powerful platform for the detection of these peptides, as the sensitivity and selectivity of the mass spectrometer is complemented by the rapid separation and filtering capabilities of DIMS. Previous work in our group has confirmed the presence of a known leukemia peptide antigen, CG1 (FLLPTGAEA), in leukemia cell lines using DIMS-MS. Peptides isolated from the U937.A2 leukemia cell line were analyzed using CG1 as a positive control to understand the impact of peptide isolation work flow. Mixtures of the predicted peptide standards were used as models for DIMS separation. The effects of dispersion field strength, carrier gas temperature, and addition of solvent modifiers on the separation and transmission of peptide antigens were explored and used to optimize detection methods.