Micro-Environment, Immunotherapy & Digital Biomarkers
The success of CAR-T and bispecific antibodies depends on both the T cells and the bone-marrow environment. We profile immune subsets, cytokines and even wearable-device data to understand and predict treatment outcomes and toxicities.
Determinants of sustained response to CAR T
We performed CITE-seq, CyTOF, and cytokine profiling of MM patients who received CAR T therapy, linking durable responses (>5 years) to early expansion of CD4 and CD8 central-memory CAR-T cells, increased diversity in TCR repertoire, and low myeloid-derived suppressor cell levels. [more]
Immune correlates of response to Talquetamab
Multi-omics analysis of Talquetamab-treated patients showed higher baseline GPRC5D expression and CD8 effector-memory T-cells predict deeper, longer responses. In vitro assays revealed that combined PD-1 + Tim-3 blockade doubles Tal-mediated cytotoxicity, pointing to a rational resistance-mitigation strategy. [more]
Wearable devices to predict CRS in CAR T therapy
Analysis of continuous vitals from wearable devices augmented with cytokine panels in CAR-T recipients detected Cytokine Release Syndrome onset a median 7 hours before nurse detection, with 80–85 % prediction accuracy. This demonstrates feasibility of outpatient monitoring when combined with proteomic markers like IFN-γ.
CAR T-related lymphoma in MM patient
We recently described a clonal CAR+ peripheral T-cell lymphoma arising six months post anti-BCMA CAR-T. WGS found a TET2-mutant clone and a CAR insertion disrupting TIA1. Complete remission was achieved with anti-CCR4 therapy, highlighting need to surveil clonal hematopoiesis and offering a targeted salvage path.
Ongoing projects
Spatial Profiling of Extra-Medullary Myeloma
We are applying multiplex spatial transcriptomics and proteomics to post-immunotherapy lesions to pinpoint drug-protected niches and new targets that could prevent or treat off-marrow spread.