Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study

被引：217

作者：

Kuebler, Hubert ^{[1
]}

Scheel, Birgit ^{[2
]}

Gnad-Vogt, Ulrike ^{[2
]}

Miller, Kurt ^{[3
]}

Schultze-Seemann, Wolfgang ^{[4
]}

vom Dorp, Frank ^{[5
]}

Parmiani, Giorgio ^{[6
]}

Hampel, Christian ^{[7
]}

Wedel, Steffen ^{[8
]}

Trojan, Lutz ^{[9
]}

Jocham, Dieter ^{[10
]}

Maurer, Tobias ^{[1
]}

Rippin, Gerd ^{[11
]}

Fotin-Mleczek, Mariola ^{[2
]}

von der Muelbe, Florian ^{[2
]}

Probst, Jochen ^{[2
]}

Hoerr, Ingmar ^{[2
]}

Kallen, Karl-Josef ^{[2
]}

Lander, Thomas ^{[2
]}

Stenzl, Arnulf ^{[12
]}

机构：

[1] Tech Univ Munich, Klinikum Rechts Isar, D-80290 Munich, Germany

[2] CureVac GmbH, Paul Ehrlich Str 15, D-72076 Tubingen, Germany

[3] Charite, Berlin, Germany

[4] Univ Hosp Freiburg, Freiburg, Germany

[5] Univ Hosp Essen, Essen, Germany

[6] Ist Sci San Raffaele, I-20132 Milan, Italy

[7] Johannes Gutenberg Univ Mainz, Univ Hosp, D-55122 Mainz, Germany

[8] Ortenau Klinikum Offenburg Gengenbach, Offenburg, Germany

[9] Univ Hosp Gottingen, Gottingen Univ Hosp Mannheim, Mannheim, Germany

[10] Univ Hosp Schleswig Holstein, Lubeck, Germany

[11] Rippin Consulting, Solingen, Germany

[12] Univ Tubingen Hosp, Tubingen, Germany

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2015年 / 3卷

基金：

欧洲研究理事会;

关键词：

STEM-CELL ANTIGEN; MEMBRANE ANTIGEN; DIRECT-INJECTION; T-LYMPHOCYTES; IN-VIVO; VACCINES; EXPRESSION; SURVIVAL; TRIAL; IMMUNOTHERAPY;

D O I：

10.1186/s40425-015-0068-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive (R)) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer. Methods: 44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts of 3-6 patients to determine a recommended dose. In phase II, 32 additional patients were treated at the recommended dose. The primary endpoint was safety and tolerability, the secondary endpoint was induction of antigen specific immune responses monitored at baseline and at weeks 5, 9 and 17. Results: The most frequent adverse events were grade 1/2 injection site erythema, injection site reactions, fatigue, pyrexia, chills and influenza-like illness. Possibly treatment related urinary retention occurred in 3 patients. The recommended dose was 1280 mu g. A total of 26/33 evaluable patients treated at 1280 mu g developed an immune response, directed against multiple antigens in 15 out of 33 patients. One patient showed a confirmed PSA response. In the subgroup of 36 metastatic patients, the Kaplan-Meier estimate of median overall survival was 31.4 months [95 % CI: 21.2; n.a]. Conclusions: The self-adjuvanted RNActive (R) vaccine CV9103 was well tolerated and immunogenic. The technology is a versatile, fast and cost-effective platform allowing for creation of vaccines. The follow-up vaccine CV9104 including the additional antigens prostatic acid phosphatase (PAP) and Muc1 is currently being tested in a randomized phase IIb trial to assess the clinical benefit induced by this new vaccination approach.

引用

页数：14

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