Single-Cell BioMEMS Tools for Monitoring Cancer Immunotherapy

I will begin with discussing a novel bioMEMS device technology for single-cell immune function profiling, in particular, the co-detection of 40+ cytokines/chemokines at the level of single cells, representing the highest multiplexing recorded to date for a single-cell protein secretion assay.

I will describe how this microdevice called IsoCode was conceived, evolved over generations, further integrated with a fully automated single-cell processing platform called IsoLight comprising high-resolution optics, precision fluid handling and live cell incubation in the same system to truly enable robust and reproducible functional proteomics data at the single-cell level.

It has been widely used in immuno-oncology trial centers and pharmaceutical companies like Novartis, Kite Pharma (a Gilead Company), Bellicum, and many others to evaluate their cellular immunotherapy products. This microchip technology allowed for the full-spectrum dissection of T cell functions including genetically engineered chimeric antigen receptor T cells (CAR-T) in the treatment of patients with acute lymphoblastic leukemia or non-Hodgkin’s lymphoma.

Our data obtained from a medium-scale clinical trial with CD19 CAR-T cells demonstrated strong association between CAR-T cells’ polyfunctionality (the ability for a single T cell to co-produce multiple immune effector proteins) and patient response, which opens up new opportunities for predicting not only therapeutic efficacy but also potentially life-threatening immunotoxicity.

Recently, we further developed a standalone portable microchip for single-cell mRNA sequencing, which was combined with single-cell protein profiling to further elucidate the activation mechanisms of engineered T cells and facilitate the development of next-generation immunotherapies.

Speaker: Rong Fan, Yale Univ.