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

   

Authors:	Tsukahara, T.; Ohmine, K.; Yamamoto, C.; Uchibori, R.; Ido, H.; Teruya, T.; Urabe, M.; Mizukami, H.; Kume, A.; Nakamura, M.; Mineno, J.; Takesako, K.; Riviere, I.; Sadelain, M.; Brentjens, R.; Ozawa, K.
Article Title:	CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models
Abstract:	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. © 2013 Elsevier Inc.
Keywords:	survival; controlled study; nonhuman; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; animal tissue; mus; interleukin 2; gene expression; animal experiment; animal model; in vitro study; tumor xenograft; cell line, tumor; mice, inbred balb c; b cell lymphoma; lymphoma, b-cell; tumor targeting; gamma interferon; retrovirus vector; transgene; chimeric antigen receptor; adoptive transfer; tumor growth; adoptive immunotherapy; cd19 antigen; antigens, cd19; cd28 antigen; peripheral lymphocyte; b-cell lymphoma; adoptive t-cell therapy; cd3 antibody; protein engineering; cd19; car; cd19-car t-cells; cd19-specific car-transduced t-cells
Journal Title:	Biochemical and Biophysical Research Communications
Volume:	438
Issue:	1
ISSN:	0006-291X
Publisher:	Elsevier Science, Inc.
Date Published:	2013-08-16
Start Page:	84
End Page:	89
Language:	English
DOI:	10.1016/j.bbrc.2013.07.030
PROVIDER:	scopus
PUBMED:	23872144
PMCID:	PMC5554955
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84881546681&partnerID=40&md5=e6490a8c758ac0ddc63627f3c000d7b1
Notes:	--- - "Export Date: 4 September 2013" - "CODEN: BBRCA" - "Source: Scopus"