Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models.
Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models.
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对移植到人源化小鼠模型中的三阴性乳腺癌患者来源的异种移植肿瘤进行基于抗 PD-1 的治疗的评估。
DOI：
10.1186/s13058-018-1037-4
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发表时间：
2018-09-05
期刊：
影响因子：
--
通讯作者：
Chang JC
中科院分区：
文献类型：
--
作者：
Rosato RR;Dávila-González D;Choi DS;Qian W;Chen W;Kozielski AJ;Wong H;Dave B;Chang JC
Breast cancer has been considered not highly immunogenic, and few patients benefit from current immunotherapies. However, new strategies are aimed at changing this paradigm. In the present study, we examined the in vivo activity of a humanized anti-programmed cell death protein 1 (anti-PD-1) antibody against triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) tumor models. To circumvent some of the limitations posed by the lack of appropriate animal models in preclinical studies of immunotherapies, partially human leukocyte antigen-matched TNBC PDX tumor lines from our collection, as well as human melanoma cell lines, were engrafted in humanized nonobese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice obtained by intravenous injection of CD34+ hematopoietic stem cells into nonlethally irradiated 3–4-week-old mice. After both PDXs and melanoma cell xenografts reached ~ 150–200 mm3, animals were treated with humanized anti-PD-1 antibody or anti-CTLA-4 and evaluated for tumor growth, survival, and potential mechanism of action. Human CD45+, CD20+, CD3+, CD8+, CD56+, CD68+, and CD33+ cells were readily identified in blood, spleen, and bone marrow collected from hNSG, as well as human cytokines in blood and engrafted tumors. Engraftment of TNBC PDXs in hNSG was high (~ 85%), although they grew at a slightly slower pace and conserved their ability to generate lung metastasis. Human CD45+ cells were detectable in hNSG-harbored PDXs, and consistent with clinical observations, anti-PD-1 antibody therapy resulted in both a significant reduction in tumor growth and increased survival in some of the hNSG PDX tumor lines, whereas no such effects were observed in the corresponding non-hNSG models. This study provides evidence associated with anti-PD-1 immunotherapy against TNBC tumors supporting the use of TNBC PDXs in humanized mice as a model to overcome some of the technical difficulties associated with the preclinical investigation of immune-based therapies. The online version of this article (10.1186/s13058-018-1037-4) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.2
作者：
Choi, Dong Soon;Blanco, Elvin;Kim, Yoo-Shin;Rodriguez, Angel A.;Zhao, Hong;Huang, Tim Hui-Ming;Chen, Chun-Liang;Jin, Guangxu;Landis, Melissa D.;Burey, Lacey A.;Qian, Wei;Granados, Sergio M.;Dave, Bhuvanesh;Wong, Helen H.;Ferrari, Mauro;Wong, Stephen T. C.;Chang, Jenny C.
通讯作者：
Chang, Jenny C.
影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
Sellers, William R.
PD-L1在指导患者选择PD-1/PD-L1抑制剂治疗中的PD-L1测试。
影响因子：
4
作者：
Ancevski Hunter K;Socinski MA;Villaruz LC
通讯作者：
Villaruz LC
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators