CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models.
CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models.
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DOI：
10.1016/j.bbrc.2013.07.030
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发表时间：
2013-08-16
影响因子：
3.1
通讯作者：
Ozawa K
中科院分区：
文献类型：
--
作者：
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
使用CD 19特异性嵌合抗原受体（汽车）的连续性T细胞疗法有希望用于治疗晚期B细胞恶性肿瘤。CAR修饰的T细胞的肿瘤靶向可能有助于治疗效力;因此，我们检查了CD 19特异性CAR（CD 19-CAR）转导的T细胞在CD 19+肿瘤病变处积累的能力与其在异种移植小鼠模型中提供抗肿瘤作用的能力之间的关系。用编码CD 19-CAR的逆转录病毒载体转导用固定的RetroNectin和抗CD 3抗体活化的正常人外周血淋巴细胞。具有约75%的高转基因表达水平的扩增的⑶ 19-CAR T细胞响应于⑶ 19产生IL-2和IFN-γ，并裂解Raji和Daudi ⑶ 19+人B细胞淋巴瘤细胞系。此外，这些细胞在Raji肿瘤病变处有效积累，与对照组相比，它们抑制了肿瘤进展并延长了荷瘤Rag 2 −/− γc−/−免疫缺陷小鼠的存活时间。这些结果表明，CD 19-CAR T细胞归巢于肿瘤病变的能力对于它们在我们的异种移植模型中的抗肿瘤作用至关重要，因此可以增强过继性T细胞疗法对难治性B细胞淋巴瘤的疗效。
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 antitumor 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.
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DOI：
10.1182/asheducation-2012.1.143
发表时间：
2012
期刊：
Hematology. American Society of Hematology. Education Program
影响因子：
--
作者：
Brentjens RJ;Curran KJ
通讯作者：
Curran KJ
影响因子：
20.3
作者：
Kochenderfer, James N.;Wilson, Wyndham H.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
12.4
作者：
Zhong, Xiao-Song;Matsushita, Maiko;Sadelain, Michel
通讯作者：
Sadelain, Michel
带有嵌合抗原受体的T细胞具有有效的抗肿瘤作用，可以在晚期白血病患者中建立记忆。
影响因子：
17.1
作者：
Kalos M;Levine BL;Porter DL;Katz S;Grupp SA;Bagg A;June CH
通讯作者：
June CH