A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer

被引：452

作者：

Ott, Patrick A. ^{[1
,2
]}

Hu-Lieskovan, Siwen ^{[3
]}

Chmielowski, Bartosz ^{[3
]}

Govindan, Ramaswamy ^{[4
]}

Naing, Aung ^{[5
]}

Bhardwaj, Nina ^{[6
]}

Margolin, Kim ^{[7
]}

Awad, Mark M. ^{[1
,2
]}

Hellmann, Matthew D. ^{[8
]}

Lin, Jessica J. ^{[2
,9
]}

Friedlander, Terence ^{[10
]}

Bushway, Meghan E. ^{[11
]}

Balogh, Kristen N. ^{[11
]}

Sciuto, Tracey E. ^{[11
]}

Kohler, Victoria ^{[11
]}

Turnbull, Samantha J. ^{[11
]}

Besada, Rana ^{[11
]}

Curran, Riley R. ^{[11
]}

Trapp, Benjamin ^{[11
]}

Scherer, Julian ^{[11
]}

Poran, Asaf ^{[11
]}

Harjanto, Dewi ^{[11
]}

Barthelme, Dominik ^{[11
]}

Ting, Ying Sonia ^{[11
]}

Dong, Jesse Z. ^{[11
]}

Ware, Yvonne ^{[11
]}

Huang, Yuting ^{[11
]}

Huang, Zhengping ^{[11
]}

Wanamaker, Amy ^{[11
]}

Cleary, Lisa D. ^{[11
]}

Moles, Melissa A. ^{[11
]}

Manson, Kelledy ^{[11
]}

Greshock, Joel ^{[11
]}

Khondker, Zakaria S. ^{[11
]}

Fritsch, Ed ^{[11
]}

Rooney, Michael S. ^{[11
]}

DeMario, Mark ^{[11
]}

Gaynor, Richard B. ^{[11
]}

Srinivasan, Lakshmi ^{[11
]}

机构：

[1] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[4] Washington Univ, Sch Med, St Louis, MO USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA

[6] Icahn Sch Med, Tisch Canc Inst, New York, NY USA

[7] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA

[8] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[9] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[10] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA 94143 USA

[11] Neon Therapeut BioNTech US, Cambridge, MA 02139 USA

来源：

CELL | 2020年 / 183卷 / 02期

关键词：

METASTATIC UROTHELIAL CARCINOMA; OPEN-LABEL; CHECKPOINT BLOCKADE; PD-1; BLOCKADE; NIVOLUMAB; IMMUNOTHERAPY; MULTICENTER; GENERATION; RESPONSES; RECEPTOR;

D O I：

10.1016/j.cell.2020.08.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase lb clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4(+) and CD8(+) T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors.

引用

页码：347 / +

页数：40

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