Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Collagen density regulates the activity of tumor-infiltrating T cells

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Juliane Schuhmacher
  • Sonja Heidu
  • Torben Balchen
  • Jennifer Rebecca Richardson
  • Camilla Schmeltz
  • Jesper Sonne
  • Jonas Schweiker
  • Hans-Georg Rammensee
  • Per Thor Straten
  • Martin Andreas Røder
  • Klaus Brasso
  • Cécile Gouttefangeas
View graph of relations

BACKGROUND: Peptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells.

METHODS: Twenty-two patients who had previously undergone radical prostatectomy received subcutaneous injections of 0.1 mg of a single RhoC-derived 20mer peptide emulsified in Montanide ISA-51 every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. The drug safety and vaccine-specific immune responses were assessed during treatment and thereafter within a 13-month follow-up period. Serum level of prostate-specific antigen was measured up to 26 months postvaccination.

RESULTS: Most patients (18 of 21 evaluable) developed a strong CD4 T cell response against the vaccine, which lasted at least 10 months following the last vaccination. Three promiscuouslypresented HLA-class II epitopes were identified. Vaccine-specific CD4 T cells were polyfunctional and effector memory T cells that stably expressed PD-1 (CD279) and OX-40 (CD134), but not LAG-3 (CD223). One CD8 T cell response was detected in addition. The vaccine was well tolerated and no treatment-related adverse events of grade ≥3 were observed.

CONCLUSION: Targeting of RhoC induced a potent and long-lasting T cell immunity in the majority of the patients. The study demonstrates an excellent safety and tolerability profile. Vaccination against RhoC could potentially delay or prevent tumor recurrence and metastasis formation.

TRIAL REGISTRATION NUMBER: NCT03199872.

Original languageEnglish
JournalJournal for ImmunoTherapy of Cancer
Volume8
Issue number2
ISSN2051-1426
DOIs
Publication statusPublished - Nov 2020

ID: 61244421