@article{01067d038031472cb597bf0c0fe1f82b,
title = "Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids",
abstract = "Chimeric antigen receptor (CAR-) T cells are revolutionizing cancer treatment, as a direct result of their clinical impact on the treatment of hematological malignancies. However for solid tumors, CAR-T cell therapeutic efficacy remains limited, primarily due to the complex immunosuppressive tumor microenvironment, inefficient access to tumor cells and poor persistence of the killer cells. In this in vitro study, an injectable, gelatin-based micro-hydrogel system that can encapsulate and deliver effective CAR-T therapy is investigated. CAR-T cells targeting TAG-72, encapsulated in these microgels possessed high viability (> 87%) after 7 days, equivalent to those grown under normal expansion conditions, with retention of the T cell phenotype and functionality. Microgel recovered CAR-T cells demonstrated potent on-target cytotoxicity against human ovarian cancer in vitro and on three-dimensional tumor spheroids, by completely eliminating tumor cells. The gelatin-based micro-hydrogels have the potential to serve as carrier systems to augment CAR-T immunotherapeutic treatment of solid tumors.",
keywords = "CAR-T cells, Cell delivery, Cell encapsulation, Immunotherapy, Microgels, Tumor spheroids",
author = "Suraiya, {Anisha B.} and Evtimov, {Vera J.} and Truong, {Vinh X.} and Boyd, {Richard L.} and Forsythe, {John S.} and Boyd, {Nicholas R.}",
note = "Funding Information: This study was supported by Cartherics Pty, Ltd, Australia and the Australian Research Council Discovery Project DP160101591 awarded to J.S.F. The authors acknowledge the use of facilities at Monash Micro Imaging (MMI, Monash University) and MMI-Monash Health Translation Precinct (MMI-MHTP). We also thank Dr Sarah Creed (MMI-MHTP) for the help with real-time imaging and analyses. A.B.S acknowledges support from the Australian Government Research Training Program (RTP) Scholarship and CRC-P for Allogeneic Stem Cell Cancer lmmunotherapies top-up scholarship. Funding Information: This study was supported by Cartherics Pty, Ltd, Australia and the Australian Research Council Discovery Project DP160101591 awarded to J.S.F. The authors acknowledge the use of facilities at Monash Micro Imaging (MMI, Monash University) and MMI-Monash Health Translation Precinct (MMI-MHTP). We also thank Dr Sarah Creed (MMI-MHTP) for the help with real-time imaging and analyses. A.B.S acknowledges support from the Australian Government Research Training Program (RTP) Scholarship and CRC-P for Allogeneic Stem Cell Cancer lmmunotherapies top-up scholarship. Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = oct,
doi = "10.1016/j.tranon.2022.101477",
language = "English",
volume = "24",
journal = "Translational Oncology",
issn = "1936-5233",
publisher = "Neoplasia Press",
}