Comprehensive immune monitoring of clinical trials to advance human immunotherapy
Hartmann et al. Cell Rep (2019)
Immune monitoring has been used to study how drugs work and to identify signals within the immune system that can predict whether a drug treatment is likely to succeed. Conventional flow cytometry has traditionally been used for immune monitoring of clinical trials, but a typical panel taps out at around 6-10 markers. Matthew Spitzer, UCSF Associate Professor and scientific cofounder of Teiko Bio, is a senior author on this paper where they team developed a 33-marker mass cytometry panel with 10 open channels for customization that can be used to characterize all major human immune cell lineages.
The researchers selected phenotypic markers to identify and classify major immune cell populations, including T cells and their subpopulations, B cells at various stages of maturation, and subsets of NK cells, among others. They also included functional state markers to determine activation states, proliferation, exhaustion states, and levels of immune checkpoint molecules.
To validate the panel’s coverage of immune subsets and replicability, the researchers profiled peripheral blood mononuclear cells (PBMCs) from healthy donors, and successfully assigned 98% of the cells to their corresponding immune cell lineages and functional subsets. Next, the panel was tested on PBMC samples from five healthy donors that were sent to two different research centers, where they were run using different instruments, reagents, and operators. The results showed a strong correlation between the two runs, with an r-value of 0.96. Additionally, this mass cytometry panel demonstrated high agreement with four flow cytometry panels that used the same markers, with an r-value of 0.98.
Panel clinical utilization in GvHD
Researchers validated the effectiveness of this panel on bone marrow from 15 patients with leukemia who underwent bone marrow transplantation and found that a reduction in CD27- B cells and the frequency of naive CD4+ T cells were associated with the development of graft-versus-host disease. This demonstrates the clinical utility of the panel in predicting and monitoring responses to treatment.
The paper highlights the value of utilizing a standardized mass cytometry panel for comprehensive immune profiling of all major immune subsets in clinical trial samples. This approach not only supports clinical development but also enables the identification of important biomarkers that may inform personalized treatment strategies.
Reference Citation: Hartmann FJ, Babdor J, Gherardini PF, Amir ED, Jones K, Sahaf B, Marquez DM, Krutzik P, O’Donnell E, Sigal N, Maecker HT, Meyer E, Spitzer MH, Bendall SC. Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy. Cell Rep. 2019 Jul 16;28(3):819-831.e4. doi: 10.1016/j.celrep.2019.06.049.