CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models

Autor: Ken Ohmine, Akihiro Kume, Michel Sadelain, Hiroyuki Ido, Tomonori Tsukahara, Ryosuke Uchibori, Chihiro Yamamoto, Junichi Mineno, Masataka Nakamura, Masashi Urabe, Hiroaki Mizukami, Takeshi Teruya, Isabelle Riviere, Kazutoh Takesako, Renier J. Brentjens, Keiya Ozawa
Rok vydání: 2013
Předmět:
Zdroj: Biochemical and biophysical research communications. 438(1)
ISSN: 1090-2104
Popis: Adoptive T-cell therapy with CD19-specific chimeric antigen receptors (CARs) is promising for treatment of advanced B-cell malignancies. Tumor targeting of CAR-modified T-cells is likely to contribute therapeutic potency; therefore we examined the relationship between the ability of CD19-specific CAR (CD19-CAR)-transduced T-cells to accumulate at CD19(+) tumor lesions, and their ability to provide anti-tumor effects in xenograft mouse models. Normal human peripheral blood lymphocytes, activated with immobilized RetroNectin and anti-CD3 antibodies, were transduced with retroviral vectors that encode CD19-CAR. Expanded CD19-CAR T-cells with a high transgene expression level of about 75% produced IL-2 and IFN-γ in response to CD19, and lysed both Raji and Daudi CD19(+) human B-cell lymphoma cell lines. Furthermore, these cells efficiently accumulated at Raji tumor lesions where they suppressed tumor progression and prolonged survival in tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared to control cohorts. These results show that the ability of CD19-CAR T-cells to home in on tumor lesions is pivotal for their anti-tumor effects in our xenograft models, and therefore may enhance the efficacy of adoptive T-cell therapy for refractory B-cell lymphoma.
Databáze: OpenAIRE
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