In a recent study, researchers used IsoPlexis’ platform to understand the functional drivers of T cell persistence in response to a novel agonist. Single-cell multiplexed cytokine profiling from both murine models and patient PBMC resulted in key findings.
As part of a collaboration between IsoPlexis and UCLA, these groundbreaking findings were published in a Nature Communications article titled “Persistence of Adoptively Transferred T cells with a Kinetically Engineered IL-2 Receptor Agonist,” highlighting IsoPlexis’ functional phenotyping and polyfunctionality as correlates to response.
Insights into T Cell Persistence Using IsoCode Single-Cell Functional Phenotyping:
- Underlying mechanism of engineered IL-2 receptor agonist, PEG-IL2, from Nektar Therapeutics, and synergy with TCR therapies.
- The IsoCode functional phenotyping used to profile translational insights between early stage development of combination PEG-IL2 with ACT therapy, and clinical impact on various immune cell types.
- System polyfunctional mouse immune cell response was seen in response to PEG-IL2, which correlated to the increases of:
- homing, and
- persistence of anti-tumor T cell in vivo.
- The mechanism resulted in superior anti-tumor activity in B16-F10 murine melanoma model as well as the promotion of polyfunctional T and NK cells in peripheral blood of patients with melanoma in a phase 1 clinical trial.
- In patients, the circulating NK cell response and clear mechanistic upregulation of polyfunctional cell subsets with anti-tumor associated protein secretions across melanoma patients profiled in the clinic.
From Pre-Clinical Mouse Models to Clinical Trials
In a mouse model, mice treated with the novel agonist recruited the adoptively transferred cells into tumors, which were found to be highly polyfunctional and adept at simultaneously secreting both effector and chemoattractive cytokines. They also delivered high concentrations of functional cytokines per cell. Reported in clinical trials, these highly functional immune cells were found to be highly persistent and sustained a longer anti-tumor response.
Correlative Functional Phenotyping
Additionally, in solid tumor patients undergoing PEG-IL2 therapy, IsoPlexis’ platform revealed upregulation of circulating CD4+ and CD8+ T cells and NK cells in the clinical setting in response to this innovative therapy. The data suggests that polyfunctionality and functional phenotyping may provide a more comprehensive biomarker in solid tumor indications, accelerating insights in cancer immunology.
IsoPlexis is excited to be a part of such significant data! To learn more about how IsoPlexis’ platform can help with your next research project, contact a single-cell functional proteomics expert. Read the full Nature Communications article here.