Microengineered transplantation of human solid tumors for in vitro studies of CAR T immunotherapy

Treatment of solid malignancies using chimeric antigen receptor (CAR) T cells remains a significant challenge, but current efforts to advance this therapy are challenged by our limited capacity to probe and understand cancer-immune interactions in human solid tumors. Here, we present a microengineered platform for in vitro modeling of malignant solid tumors during CAR T therapy. This system makes it possible to vascularize human tumor explants and perfuse them with blood-borne immune cells in a controlled manner. We first present a microphysiological model of human lung adenocarcinomas infused with CAR-T cells and show how this system can be used to simulate, visualize, and interrogate tumor-directed trafficking and effector function of CAR T cells. We then demonstrate the proof-of-principle of testing a chemokine-directed CAR T cell engineering strategy in a model of malignant pleural mesothelioma and validating our in vitro assessment using a matching in vivo mouse model. Finally, we ..., , # Microengineered transplantation of human solid tumors for in vitro studies of CAR T immunotherapy

Dataset DOI: [10.5061/dryad.mw6m9068f](10.5061/dryad.mw6m9068f)

## Description of the data and file structure

Microscopic fluorescent images of human tumor constructs, microengineered blood vessels, and infused human T cells were collected in a microengineered human solid tumor model. Each folder corresponds to an individual figure in the related manuscript and contains subfolders of figure panels and/or subfolders of treatment conditions that are also described in detail below. Images were collected at various time points and treatment conditions as indicated in the folder path and file names. The filenaming convention for the image files is defined as follows: Figure number+panel label+(Tumor group, T cell group, or treatment group)+Construct ID+Culture time+(Tumor detail)+(Days post tumor transplantation)+(T cell detail)+(Days post T cell infusion)+(additional information such as im..., Primary mesothelioma explants (Meso explant) were derived and obtained from tumors of malignant pleural mesothelioma patients undergoing potentially curative surgery. The tumor explants were de-identified before processing and transplantation into our microengineered constructs, and informed consent was obtained from all patients.