Seminar: Bart Neyns, theme Cancer development and immune defense

Clinical trial experience with Dendritic Cell vaccines as a monotherapy or combined immune checkpoint inhibition to treat cancer

Date:
21 April 2016 10:00 hrs. - 11:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Clinical trial experience with Dendritic Cell vaccines as a monotherapy or combined immune checkpoint inhibition to treat cancer
Speaker(s):

Bart Neyns, Dept. of Medical Oncology, UZ Brussel

Host(s):

Carl Figdor, Dept. of Tumor Immunology, RIMLS

21-04-2016 10:00:0021-04-2016 11:00:00Europe/AmsterdamClinical trial experience with Dendritic Cell vaccines as a monotherapy or combined immune checkpoint inhibition to treat cancer Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

undefinedAutologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) have superior in vitro immunostimulatory properties, and are immunogenic while having no grade 3-5 treatment related toxicity as a monotherapy in patients with pretreated advanced melanoma. In a phase IB clinical trial where TriMixDC-MEL was administered by the intravenous and intradermal route, objective responses were documented in 4 out of 15 patients and these responses are ongoing after more than 5 years in 3 of these patients. In a randomized phase II clinical trial (20+21 patients) for the adjuvant treatment of melanoma patients without evidence of disease following resection of macrometastases(s), TriMixDC-MEL treatment improved the 1-year disease-free survival rate from 35% (95% CI 14-55) to 66% (46-86).  In a phase II study investigating the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma, thirty-nine patients were treated with TriMixDC-MEL (4 x 106 cells administered intradermally and 20 x 106 cells administered intravenously) plus ipilimumab (: an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function; administered at 10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). The 6-month disease control by immune-related response criteria was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post–DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients and there was no grade 5 adverse event. These results support the further clinical exploration of dendritic cell therapy in combination with immune checkpoint inhibitors.

Key Publications

  • Phase II Study of AutologousMonocyte-Derived mRNA ElectroporatedDendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma. J ClinOncol. JCO634121, 2016
  • Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporateddendritic cell therapy following complete resection of metastases. Cancer ImmunolImmunother.; 64:381-8, 2015
  • A phase IB study on intravenous synthetic mRNA electroporateddendritic cell immunotherapy in pretreated advanced melanoma patients. Ann Oncol.;24:2686-93, 2013.
  • Therapeutic vaccination with an autologous mRNA electroporateddendritic cell vaccine in patients with advanced melanoma. J Immunother.;34:448-56, 2011


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