Short-Interval Sequential CAR-T Cell Infusion May Enhance Prior CAR-T Cell Expansion to Augment Anti-Lymphoma Response in B-NHL.
Short-Interval Sequential CAR-T Cell Infusion May Enhance Prior CAR-T Cell Expansion to Augment Anti-Lymphoma Response in B-NHL.
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短时间连续 CAR-T 细胞输注可能会增强之前的 CAR-T 细胞扩增，从而增强 B-NHL 的抗淋巴瘤反应
DOI：
10.3389/fonc.2021.640166
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发表时间：
2021
影响因子：
4.7
通讯作者：
Pan J
中科院分区：
文献类型：
--
作者：
Meng Y;Deng B;Rong L;Li C;Song W;Ling Z;Xu J;Duan J;Wang Z;Chang AH;Feng X;Xiong X;Chen X;Pan J
嵌合抗原受体(CAR)-T细胞治疗是治疗难治性或复发性(r/r)B细胞性非霍奇金淋巴瘤(B-NHL)的一种新方法，但B-NHL患者的总有效率(ORR)明显低于r/r B急性淋巴细胞白血病(B-ALL)患者。我们此前证实，CD20和CD22 CAR-T细胞的序贯输注显著改善了B-NHL患者的预后，而在这些CAR-T细胞治疗期间，一些晚期患者仍进展至死亡。在本研究中，我们证明了适时连续给药第二批CAR-T细胞可以促进先前CAR-T细胞的扩增，在体内外具有更强的杀瘤能力。我们进一步对两名晚期B-NHL患者进行了同情治疗，并进行了CD19/22/20 CAR-T细胞的短间隔顺序输注。两名患者在一次CAR-T细胞输注后均观察到疾病进展，但二次CAR-T细胞输注可诱导先前CAR-T细胞的强劲再扩增和抗肿瘤作用。这些结果表明，短间隔顺序输注CAR-T细胞可通过促进原有CAR-T细胞的扩增来提高B-NHL患者的治疗效果。
Chimeric antigen receptor (CAR)-T cell therapy emerges as a new treatment for refractory or relapsed (r/r) B-cell non-Hodgkin lymphoma (B-NHL); however, the overall response rate (ORR) of which in the B-NHL patients is much lower compared to the patients with r/r B acute lymphoblastic leukemia (B-ALL). We previously confirmed that sequential infusions of CD20 and CD22 CAR-T cells significantly improved the prognosis of the B-NHL patients, while some advanced patients still progressed to death during these CAR-T cell treatments. In this study, we showed that timely sequential administration of the second CAR-T cells could enhance expansion of prior CAR-T cells with stronger tumor-killing capacity in vitro and in vivo. We further conducted compassionate treatments on two advanced B-NHL patients with short-interval sequential infusions of CD19/22/20 CAR-T cells. Disease progression was observed in both patients after primary CAR-T cell infusion but robust re-expansion of prior CAR-T cells and anti-tumor effects was induced by infusion of a secondary CAR-T cells. These results indicate sequential infusions of CAR-T cells with a short interval may improve therapeutic efficacy in the B-NHL patients by promoting expansion of prior CAR-T cells.
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DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
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
序贯 CD19-22 CAR T 疗法可诱导 r/r B-ALL 儿童持续缓解
影响因子：
20.3
作者：
Pan, Jing;Zuo, Shiyu;Tong, Chunrong
通讯作者：
Tong, Chunrong
影响因子：
45.3
作者：
Kochenderfer, James N.;Somerville, Robert P. T.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
20.3
作者：
Yang, Zhi-Zhang;Grote, Deanna M.;Ansell, Stephen M.
通讯作者：
Ansell, Stephen M.