Cargando…

Efficient derivation of chimeric-antigen receptor-modified T(SCM) cells

Chimeric-antigen receptor (CAR) T-cell immunotherapy employs autologous-T cells modified with an antigen-specific CAR. Current CAR-T manufacturing processes tend to yield products dominated by effector T cells and relatively small proportions of long-lived memory T cells. Those few cells are a so-ca...

Descripción completa

Detalles Bibliográficos
Autores principales: Kranz, Emiko, Kuhlmann, Charles J., Chan, Joshua, Kim, Patrick Y., Chen, Irvin S. Y., Kamata, Masakazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366550/
https://www.ncbi.nlm.nih.gov/pubmed/35967430
http://dx.doi.org/10.3389/fimmu.2022.877682
Descripción
Sumario:Chimeric-antigen receptor (CAR) T-cell immunotherapy employs autologous-T cells modified with an antigen-specific CAR. Current CAR-T manufacturing processes tend to yield products dominated by effector T cells and relatively small proportions of long-lived memory T cells. Those few cells are a so-called stem cell memory T (T(SCM)) subset, which express naïve T-cell markers and are capable of self-renewal and oligopotent differentiation into effector phenotypes. Increasing the proportion of this subset may lead to more effective therapies by improving CAR-T persistence; however, there is currently no standardized protocol for the effective generation of CAR-T(SCM) cells. Here we present a simplified protocol enabling efficient derivation of gene-modified T(SCM) cells: Stimulation of naïve CD8+ T cells with only soluble anti-CD3 antibody and culture with IL-7 and IL-15 was sufficient for derivation of CD8+ T cells harboring T(SCM) phenotypes and oligopotent capabilities. These in-vitro expanded T(SCM) cells were engineered with CARs targeting the HIV-1 envelope protein as well as the CD19 molecule and demonstrated effector activity both in vitro and in a xenograft mouse model. This simple protocol for the derivation of CAR-T(SCM) cells may facilitate improved adoptive immunotherapy.