Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial.

Abstract

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.

• Authors: Redas Trepiakas, Annika Berntsen, Sine Reker Hadrup, Jon Bjørn, Poul F Geertsen, Per Thor Straten, Mads H Andersen, Anders E Pedersen, Amir Soleimani, Torben Lorentzen, Julia S Johansen, Inge Marie Svane
• Journal: Cytotherapy (Cytotherapy) Vol. 12 Issue 6 Pg. 721-34 (Oct 2010) ISSN: 1477-2566 [Electronic] England
• PMID: 20429791 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• HLA-A2 Antigen
• Interferon-alpha
• Interleukin-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (immunology, metabolism)
• Cancer Vaccines
• Cells, Cultured
• Dendritic Cells (immunology, metabolism, pathology, transplantation)
• Female
• Follow-Up Studies
• HLA-A2 Antigen (metabolism)
• Humans
• Interferon-alpha (administration & dosage)
• Interleukin-2 (administration & dosage)
• Lymphocyte Activation
• Male
• Melanoma (immunology, mortality, pathology, physiopathology, therapy)
• Middle Aged
• Skin Neoplasms (immunology, mortality, pathology, physiopathology, therapy)
• Survival Analysis
• T-Lymphocytes (immunology, metabolism, pathology)