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@ARTICLE{FresnilloSal:300824,
      author       = {S. Fresnillo Saló and J. Schuhmacher and A. Rahbech and S.
                      R. Pedersen and T. Seremet and V. A. Matillas and A.
                      Schöllhorn and A. Røder and S. W. Jørgensen and K. Brasso
                      and C. Gouttefangeas$^*$ and P. T. Straten and On Behalf Of
                      The RhoVac-Study Group},
      title        = {{V}accination {A}gainst {R}ho{C} in {P}rostate {C}ancer
                      {P}atients {I}nduces {P}otent and {L}ong-{L}asting {CD}4+
                      {T} {C}ell {R}esponses with {C}ytolytic {P}otential in the
                      {A}bsence of {C}linical {E}fficacy: {A} {R}andomized {P}hase
                      {II} {T}rial.},
      journal      = {Vaccines},
      volume       = {13},
      number       = {4},
      issn         = {2076-393X},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2025-00938},
      pages        = {390},
      year         = {2025},
      abstract     = {Background: A previous phase I/II study demonstrated potent
                      and long-term immune responses in men with prostate cancer
                      following vaccination with a 20mer synthetic peptide (RV001)
                      derived from the Ras homolog gene family member C protein
                      (RhoC). Moreover, a fraction of patients experienced
                      prostate-specific antigen (PSA) responses, which prompted
                      the initiation of a phase II double-blind randomized trial
                      (NCT04114825). The primary endpoint was to study whether
                      vaccination could postpone PSA progression. Furthermore, the
                      study included an evaluation of vaccination-induced immune
                      responses, and in-depth in vitro studies of RhoC-specific
                      CD4+ T cell responses. Methods: Men with non-metastatic
                      biochemical recurrence after either radical prostatectomy or
                      radiation therapy were eligible for the study. Participants
                      were randomized 1:1 to either subcutaneous injections of 0.1
                      mg/mL RV001 emulsified in Montanide ISA 51, or a placebo.
                      Vaccinations were administered every 2 weeks for the first
                      six times, then five times every 4 weeks for a total
                      treatment time of 30 weeks. Blood samples were collected
                      from a subset of patients (n = 38) over the course of
                      vaccination, and peripheral blood mononuclear cells (PBMCs)
                      isolated for immunological assessment of vaccine-induced
                      immune responses. Experiments using PBMCs from a healthy
                      donor and a patient were performed to study the phenotype
                      and function of RV001-specific CD4+ T cells. Results: A
                      total of 192 men entered the study. There was no difference
                      in time to PSA doubling, with 7.5 versus 9.3 months, or in
                      time to initiating further therapies, 11.2 versus 17.6
                      months for treatment and control groups, respectively. At
                      long-term follow-up, $12.9\%$ of the patients in the
                      vaccination arm had developed metastasis compared to $12\%$
                      in the placebo arm. No serious treatment-related side
                      effects were observed, and treatment-related adverse events
                      did not differ between groups. Immunological examinations in
                      a subset of patients demonstrated that the vaccination
                      induced potent, long-lasting CD4+ T cell responses capable
                      of proliferation and cytokine production. RV001-specific
                      CD4+ T cells were shown to mediate cytotoxicity against a
                      RhoC-expressing cancer cell line in an HLA-class
                      II-dependent manner. Conclusions: Men randomized to active
                      treatment with RV001V demonstrated the induction of potent,
                      functionally capable, anti RhoC-CD4+ T cell responses.
                      However, there was no benefit in time to biochemical
                      progression, and no difference in time to the initiation of
                      second-line therapies.},
      keywords     = {CD4+ T cells (Other) / RhoC (Other) / cancer vaccine
                      (Other)},
      cin          = {TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)TU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40333248},
      doi          = {10.3390/vaccines13040390},
      url          = {https://inrepo02.dkfz.de/record/300824},
}