Intratumoral Delivery of Chimeric Antigen Receptor T Cells Targeting CD133 Effectively Treats Brain Metastases.
Clin Cancer Res
; 30(3): 554-563, 2024 02 01.
Article
em En
| MEDLINE
| ID: mdl-37787999
ABSTRACT
PURPOSE:
Brain metastases (BM) are mainly treated palliatively with an expected survival of less than 12 months after diagnosis. In many solid tumors, the human neural stem cell marker glycoprotein CD133 is a marker of a tumor-initiating cell population that contributes to therapy resistance, relapse, and metastasis. EXPERIMENTALDESIGN:
Here, we use a variant of our previously described CD133 binder to generate second-generation CD133-specific chimeric antigen receptor T cells (CAR-T) to demonstrate its specificity and efficacy against multiple patient-derived BM cell lines with variable CD133 antigen expression.RESULTS:
Using both lung- and colon-BM patient-derived xenograft models, we show that a CD133-targeting CAR-T cell therapy can evoke significant tumor reduction and survival advantage after a single dose, with complete remission observed in the colon-BM model.CONCLUSIONS:
In summary, these data suggest that CD133 plays a critical role in fueling the growth of BM, and immunotherapeutic targeting of this cell population is a feasible strategy to control the outgrowth of BM tumors that are otherwise limited to palliative care. See related commentary by Sloan et al., p. 477.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Receptores de Antígenos Quiméricos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá