BACKGROUND AND AIM: Dendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(−) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b. RESULTS: Of 46 patients who initiated treatment, 10 stopped treatment within 1-4 weeks because of rapid disease progression and deterioration. After 8 weeks, 36 patients were evaluable: no patient had an objective response, 11 patients had stable disease (SD); six had continued SD after 4 months, and three patients had prolonged SD for more than 6 months. The mean overall survival time was 9 months, with a significantly longer survival (18.4 months) of patients who attained SD compared with patients with progressive disease (PD) (5 months). Induction of antigen-specific T-cell responses was analyzed by multidimensional encoding of T cells using HLA-A2 major histocompatibility complex (MHC) multimers. Immune responses against five high-affinity vaccine peptides were detectable in the peripheral blood of six out of 10 analyzed HLA-A2+ patients. There was no observed correlation between the induction of immune responses and disease stabilization. A significant lower blood level of regulatory T cells (CD25(high) CD4 T cells) was demonstrable after six vaccinations in patients with SD compared with PD. CONCLUSIONS: Vaccination was feasible and safe. Treatment-associated SD was observed in 24% of the patients. SD correlated with prolonged survival suggesting a clinical benefit. Differences in the level of regulatory T cells among SD and PD patients could indicate a significant role of these immune suppressive cells.
BACKGROUND AND AIM: Dendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(−) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b. RESULTS: Of 46 patients who initiated treatment, 10 stopped treatment within 1-4 weeks because of rapid disease progression and deterioration. After 8 weeks, 36 patients were evaluable: no patient had an objective response, 11 patients had stable disease (SD); six had continued SD after 4 months, and three patients had prolonged SD for more than 6 months. The mean overall survival time was 9 months, with a significantly longer survival (18.4 months) of patients who attained SD compared with patients with progressive disease (PD) (5 months). Induction of antigen-specific T-cell responses was analyzed by multidimensional encoding of T cells using HLA-A2 major histocompatibility complex (MHC) multimers. Immune responses against five high-affinity vaccine peptides were detectable in the peripheral blood of six out of 10 analyzed HLA-A2+ patients. There was no observed correlation between the induction of immune responses and disease stabilization. A significant lower blood level of regulatory T cells (CD25(high) CD4 T cells) was demonstrable after six vaccinations in patients with SD compared with PD. CONCLUSIONS: Vaccination was feasible and safe. Treatment-associated SD was observed in 24% of the patients. SD correlated with prolonged survival suggesting a clinical benefit. Differences in the level of regulatory T cells among SD and PDpatients could indicate a significant role of these immune suppressive cells.
Authors: Jamal S Lewis; Natalia V Dolgova; Ying Zhang; Chang Qing Xia; Clive H Wasserfall; Mark A Atkinson; Michael J Clare-Salzler; Benjamin G Keselowsky Journal: Clin Immunol Date: 2015-04-02 Impact factor: 3.969
Authors: Stefanie Gross; Michael Erdmann; Ina Haendle; Steve Voland; Thomas Berger; Erwin Schultz; Erwin Strasser; Peter Dankerl; Rolf Janka; Stefan Schliep; Lucie Heinzerling; Karl Sotlar; Pierre Coulie; Gerold Schuler; Beatrice Schuler-Thurner Journal: JCI Insight Date: 2017-04-20
Authors: Alexandre Harari; Michele Graciotti; Michal Bassani-Sternberg; Lana E Kandalaft Journal: Nat Rev Drug Discov Date: 2020-08-06 Impact factor: 84.694
Authors: Tiffany R Hodges; Sherise D Ferguson; Hillary G Caruso; Gary Kohanbash; Shouhao Zhou; Timothy F Cloughesy; Mitchel S Berger; George H Poste; Mustafa Khasraw; Sujuan Ba; Tao Jiang; Tom Mikkelson; W K Alfred Yung; John F de Groot; Howard Fine; Lewis C Cantley; Ingo K Mellinghoff; Duane A Mitchell; Hideho Okada; Amy B Heimberger Journal: Oncoimmunology Date: 2016-02-18 Impact factor: 8.110