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Intratumoral Delivery of Chimeric Antigen Receptor T Cells Targeting CD133 Effectively Treats Brain Metastases.
Kieliszek, Agata M; Mobilio, Daniel; Upreti, Deepak; Bloemberg, Darin; Escudero, Laura; Kwiecien, Jacek M; Alizada, Zahra; Zhai, Kui; Ang, Patrick; Chafe, Shawn C; Vora, Parvez; Venugopal, Chitra; Singh, Sheila K.
Afiliação
  • Kieliszek AM; Centre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, Ontario, Canada.
  • Mobilio D; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
  • Upreti D; Centre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, Ontario, Canada.
  • Bloemberg D; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
  • Escudero L; Century Therapeutics, Hamilton, Ontario, Canada.
  • Kwiecien JM; Century Therapeutics, Hamilton, Ontario, Canada.
  • Alizada Z; Centre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, Ontario, Canada.
  • Zhai K; Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
  • Ang P; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Chafe SC; Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
  • Vora P; Centre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, Ontario, Canada.
  • Venugopal C; Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
  • Singh SK; Centre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, Ontario, Canada.
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. EXPERIMENTAL

DESIGN:

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.
Assuntos

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

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