Abstract
Adoptive cell therapy is an emerging anti-cancer modality, whereby the patient’s own immune cells are engineered to express T-cell receptor (TCR) or chimeric antigen receptor (CAR). CAR-T cell therapies have advanced the furthest, with recent approvals of two treatments by the Food and Drug Administration of Kymriah (trisagenlecleucel) and Yescarta (axicabtagene ciloleucel). Recent developments in proteomic analysis by mass spectrometry (MS) make this technology uniquely suited to enable the comprehensive identification and quantification of the relevant biochemical architecture of CAR-T cell therapies and fulfill current unmet needs for CAR-T product knowledge. These advances include improved sample preparation methods, enhanced separation technologies, and extension of MS-based proteomic to single cells. Innovative technologies such as proteomic analysis of raw material quality attributes (MQA) and final product quality attributes (PQA) may provide insights that could ultimately fuel development strategies and lead to broad implementation.
Highlights
Most of a cell’s phenotype and function are characterized by its proteome, the suite of all the proteins
The ability to understand relationships between protein expressions and cellular function have been revolutionized by proteomic methods based on high-resolution separation sciences coupled to high-resolution mass spectrometry (HRMS) instruments [3]
We provide an overview of the manufacturing process of chimeric antigen receptor (CAR)-T therapeutics, literature examples of proteomic-based measurements in CAR-T, and recent advances in proteomic technologies that are assured to extend its implementation
Summary
Most of a cell’s phenotype and function are characterized by its proteome, the suite of all the proteins. MS-based phosphoproteomics has identified signaling pathways and specific proteins that are involved in the maturation of primary T-cells [6,7] and the function of cytotoxic T-lymphocytes [8]. These same innate immune functions, such as adaptive. Yescarta is approved for the treatment of aggressive non-Hodgkin lymphoma These promising new therapies represent a revolutionary advance in treating cancer in that their mechanisms of action are orthogonal to that of chemotherapeutic and monoclonal antibody (mAb)-based modalities. A focus will be given to advanced proteomic sample preparation strategies, micro and nanoscale separation science capabilities, the emerging field of single-cell proteomics, and a perspective on proteomic measurement controls that should be considered when developing proteomic methods
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
