RESUMO
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.
RESUMO
In this issue of Cell Stem Cell, Xu et al. (2019) demonstrate that editing iPSCs' major histocompatibility antigens may potentially provide a small set of universally compatible stem cell lines for therapies. However, these modifications may result in patient minor histocompatibility responses and deficiencies in their T cell response repertoire to infection and cancer.
Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Sistemas CRISPR-Cas , Linhagem Celular , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , HumanosRESUMO
Two papers in this issue of Cell Stem Cell have made a significant advance in solving one of the great challenges of modern immunology-resurrecting thymus function through the induction of thymus epithelial cells (TECs) by directed differentiation of human embryonic stem cells (hESCs).