An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma

被引：712

作者：

Sahin, Ugur ^{[1
,2
,3
,4
]}

Oehm, Petra ^{[1
]}

Derhovanessian, Evelyna ^{[1
]}

Jabulowsky, Robert A. ^{[1
]}

Vormehr, Mathias ^{[1
]}

Gold, Maike ^{[1
]}

Maurus, Daniel ^{[1
]}

Schwarck-Kokarakis, Doreen ^{[1
]}

Kuhn, Andreas N. ^{[1
]}

Omokoko, Tana ^{[1
]}

Kranz, Lena M. ^{[1
]}

Diken, Mustafa ^{[1
,2
]}

Kreiter, Sebastian ^{[1
,2
]}

Haas, Heinrich ^{[1
]}

Attig, Sebastian ^{[2
,3
]}

Rae, Richard ^{[2
]}

Cuk, Katarina ^{[1
]}

Kemmer-Brueck, Alexandra ^{[1
]}

Breitkreuz, Andrea ^{[1
]}

Tolliver, Claudia ^{[1
]}

Caspar, Janina ^{[1
]}

Quinkhardt, Juliane ^{[1
]}

Hebich, Lisa ^{[1
]}

Stein, Malte ^{[1
]}

Hohberger, Alexander ^{[2
]}

Vogler, Isabel ^{[1
]}

Liebig, Inga ^{[1
]}

Renken, Stephanie ^{[1
]}

Sikorski, Julian ^{[1
]}

Leierer, Melanie ^{[5
,6
]}

Mueller, Verena ^{[7
,8
]}

Mitzel-Rink, Heidrun ^{[9
]}

Miederer, Matthias ^{[10
]}

Huber, Christoph ^{[1
,2
]}

Grabbe, Stephan ^{[9
]}

Utikal, Jochen ^{[7
,8
]}

Pinter, Andreas ^{[11
]}

Kaufmann, Roland ^{[11
]}

Hassel, Jessica C. ^{[5
,6
]}

Loquai, Carmen ^{[9
]}

Tuereci, Oezlem ^{[1
,4
]}

机构：

[1] BioNTech, Mainz, Germany

[2] Johannes Gutenberg Univ Mainz gGmbH, Translat Oncol Univ Med Ctr, TRON, Mainz, Germany

[3] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Res Ctr Immunotherapy FZI, Mainz, Germany

[4] Helmholtz Inst Translat Oncol Mainz, HI TRON, Mainz, Germany

[5] Heidelberg Univ Hosp, Dept Dermatol, Heidelberg, Germany

[6] Heidelberg Univ Hosp, Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[7] German Canc Res Ctr, Skin Canc Unit, Heidelberg, Germany

[8] Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, Mannheim, Germany

[9] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Dermatol, Mainz, Germany

[10] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Nucl Med, Mainz, Germany

[11] Univ Hosp Frankfurt Main, Dept Dermatol Venereol & Allergol, Frankfurt, Germany

来源：

NATURE | 2020年 / 585卷 / 7823期

关键词：

CANCER-IMMUNOTHERAPY; ANTIGENS; LIPOSOMES; HIERARCHY; ALIGNMENT;

D O I：

10.1038/s41586-020-2537-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours(1,2). We are testing melanoma FixVac (BNT111)-an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma-in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4(+)and CD8(+)T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination. Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4(+)and CD8(+)T-cell immunity.

引用

页码：107 / +

页数：24

共 36 条

[1]

Barichello JM, 2010, METHODS MOL BIOL, V605, P461, DOI 10.1007/978-1-60327-360-2_32

[2] SINGLE BILAYER LIPOSOMES PREPARED WITHOUT SONICATION [J].