- Single-cell RNA-seq reveals distinct CD45 + cells associated with clinical outcome
- The balance between two CD8 + T cell states is linked with tumor regression
- TCF7 +CD8 + T cell frequency in tumor tissue predicts response and better survival
- Dual blockade of CD39 with different checkpoint proteins enhances immunity
Cell paper on "Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma" features AIM Biotech chips for Ex Vivo Immune Checkpoint Assays to Validate Key Discoveries
Sade-Feldman et al from the Massachusetts General Hospital Cancer Center, the Broad Institute, the Dana Farber Cancer Institute and others demonstrated in the Cell paper that:
In vitro 3D cell culture models bridge the gap between conventional 2D cell culture and expensive in vivo animal models. Join our webinar, where we cover how to generate simple & complex 3D organ models for research, drug metabolism, and toxicity studies using the microfluidic 3D organ-on-a-chip from AIM Biotech. Register now at this link.
3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes
A blood-brain barrier (BBB) model is achieved by co-culturing iPSC-derived endothelial cells, human astrocytes and pericytes in microfluidic chips featuring AIM's technology. The BBB model not only exhibits physiologically relevant structures but also has permeability that is comparable to the in vivo permeability measurement in rat brain. From a recent publication in Biomaterials.
Nature Medicine paper on "Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses" employs AIM chips for in vitro immune checkpoint assays
A Nature Medicine paper by researchers from the Dana-Farber Cancer Institute, NYU and others features the discovery of a new genetic profile, SPARCS that predicts tumor immune response. The authors used AIM chips and human NSCLC biopsies to show that SPARCS_high profiles correspond with positive immune-checkpoint responses.
Dana-Farber researchers culture patient-derived tumor spheroids in AIM chips to accurately predict their in vivo response to targeted therapies
Dr Amir Aref of the Dana-Farber Cancer Institute will be sharing how short-term culture of organotypic patient tumor spheroids derived from patient xenografts in AIM chips predicts in vivo response of targeted therapies at AACR 2018 on Sunday 350pm 15th April (see the full abstract & details at this link)
Two Cancer Discovery papers feature a novel ex vivo immune checkpoint assay developed with AIM chips
Researchers at the Dana-Farber Cancer Institute and MIT have developed a novel ex vivo assay (above) to profile the PD-1 blockade, making it possible to interrogate the tumor immune microenvironment, develop novel therapeutic combinations, and facilitate precision immuno-oncology efforts. The assay is detailed by Jenkins et al in “Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids“, Cancer Discovery doi: 10.1158/2159-8290.CD-17-0833
The ex vivo organotypic tumor spheroid culture system was utilised by Deng et al to show that CDK4/6 inhibition augments the response to PD-1 blockade. The effect was validated in multiple in vivo murine syngeneic models, thereby providing a rationale for combining CDK4/6 inhibitors and immunotherapies. The results are detailed in “CDK4/6 Inhibition Augments Anti-Tumor Immunity by Enhancing T Cell Activation”, Cancer Discovery doi: 10.1158/2159-8290.CD-17-0915
Dana-Farber Cancer Institute news release (click here)
* Update 5th Sep 2018
Follow up publication: *3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade. Aref AR, Campisi M, Ivanova E, Portell A, Larios D, Piel BP... Jenkins RW. Lab on a Chip, 2018, DOI: 10.1039/C8LC00322J
Researchers from the Dana-Farber Cancer Institute presented two posters at AACR 2017:
1. Ex vivo profiling of PD-1 blockade using organotypic tumor spheroids (abstract linked here)
2. Validation of a novel microfluidic device for screening of immune checkpoint inhibitors using 3D organotypic tumor spheroids (abstract linked here)
The researchers demonstrated that they could recapitulate sensitivity and innate resistance to PD-1 blockade ex vivo with an assay developed on AIM chips. They were able to profile the functional response to tumor PD-1 blockade ex vivo and unveil a novel strategy to advance precision immuno-oncology.