Despite the progress being made in CAR T therapies, more than 50% of patients treated with CD19 CAR-T cells experience disease progression. Strategies such as creating bi-specific CAR-T cells are being employed to combat this relapse.1 One challenge that scientists face in the development of these novel therapies is the identification of critical quality indicators of potency in the manufacturing and bioprocessing process.
A recently published paper in Nature Medicine1 explored the benefits of IsoPlexis’ single-cell functional phenotyping platform for overcoming critical challenges in cell therapy manufacturing. As the only technology to reveal true functional insights, IsoPlexis’ solution enables researchers to phenotype each immune cell by its extracellular function, accelerating next generation therapy development.
In the Phase 1 clinical trial in patients with relapsed B cell acute lymphoblastic leukemia, IsoPlexis’ unique single-cell functional proteomics provided meaningful product quality insights to predict CAR potency in vivo. The data from the trial suggest that progressive disease after CD19-22.BB.z-CAR in LBCL is associated with a robust early response followed by early acquired resistance. Researchers identified a functional driver of relapse suggesting possible improvements in CAR manufacturing that could prevent antigen+ resistance.
The authors stated:
“Our results suggest that engineering iterations should be guided by careful studies of single-cell CAR polyfunctionality incorporating cytokine production as a critical quality attribute.”
In previous studies, IsoPlexis has demonstrated how our platform can reveal predictive insights across the entire cell therapy development pipeline. From preclinical in liver cancer (published in Gastroenterology) and in antigen escape (published in Blood Advances) to manufacturing and process optimization; and clinical cases (Published in Blood), the IsoPlexis platform has been shown to help researchers gain new insights into their programs.
The most recent publication from Nature Medicine further highlights how IsoPlexis is providing critical predictive metrics for the product characterization and optimization of CAR-T therapies and manufacturing workflows.
- Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M, Younes S, Natkunam Y, Ozawa MG, Yang E, Tamaresis J, Chinnasamy H, Ehlinger Z, Reynolds W, Lynn R, Rotiroti MC, Gkitsas N, Arai S, Johnston L, Lowsky R, Majzner RG, Meyer E, Negrin RS, Rezvani AR, Sidana S, Shizuru J, Weng WK, Mullins C, Jacob A, Kirsch I, Bazzano M, Zhou J, Mackay S, Bornheimer SJ, Schultz L, Ramakrishna S, Davis KL, Kong KA, Shah NN, Qin H, Fry T, Feldman S, Mackall CL, Miklos DB. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021 Jul 26. doi: 10.1038/s41591-021-01436-0.