التفاصيل البيبلوغرافية
| العنوان: |
Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial. |
| المؤلفون: |
Trepiakas, Redas, Berntsen, Annika, Hadrup, Sine Reker, Bjørn, Jon, Geertsen, Poul F., Straten, Per Thor, Andersen, Mads H., Pedersen, Anders E., Soleimani, Amir, Lorentzen, Torben, Johansen, Julia S., Svane, Inge Marie |
| المصدر: |
Cytotherapy (Taylor & Francis Ltd); Oct2010, Vol. 12 Issue 6, p721-734, 14p, 2 Charts, 3 Graphs |
| مصطلحات موضوعية: |
MELANOMA treatment, VACCINATION, DENDRITIC cells, IMMUNE response, ANTINEOPLASTIC agents, TUMOR antigens, THERAPEUTICS |
| مستخلص: |
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)-α2b. 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 (CD25high 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
