Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.

Abstract

Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-gamma in direct ELISPOT. Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-alpha-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.

• Authors: Jacques Banchereau, Hideki Ueno, Madhav Dhodapkar, John Connolly, Jennifer P Finholt, Eynav Klechevsky, Jean-Philippe Blanck, Dennis A Johnston, A Karolina Palucka, Joseph Fay
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2005 Sep-Oct Vol. 28 Issue 5 Pg. 505-16 ISSN: 1524-9557 [Print] United States
• PMID: 16113607 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD34
• Antigens, Neoplasm
• Cancer Vaccines
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Interferon Type I
• Interferon-alpha
• MAGEA3 protein, human
• MART-1 Antigen
• MLANA protein, human
• Membrane Glycoproteins
• Neoplasm Proteins
• PMEL protein, human
• Peptide Fragments
• Peptides
• Viral Matrix Proteins
• gp100 Melanoma Antigen
• Interferon-gamma
• Monophenol Monooxygenase

Topics

• Adult
• Antigens, CD34 (biosynthesis)
• Antigens, Neoplasm (biosynthesis, chemistry)
• Cancer Vaccines
• Cell Proliferation
• Dendritic Cells (cytology)
• Disease Progression
• Disease-Free Survival
• Enzyme-Linked Immunosorbent Assay
• HLA-A Antigens (biosynthesis)
• HLA-A2 Antigen
• Humans
• Immunotherapy, Adoptive (methods)
• Influenza A virus (chemistry)
• Interferon Type I (therapeutic use)
• Interferon-alpha (metabolism)
• Interferon-gamma (metabolism)
• MART-1 Antigen
• Melanoma (immunology, therapy)
• Membrane Glycoproteins (biosynthesis)
• Middle Aged
• Monophenol Monooxygenase (biosynthesis)
• Neoplasm Proteins (biosynthesis)
• Peptide Fragments (chemistry)
• Peptides (therapeutic use)
• Stem Cells (cytology)
• Time Factors
• Treatment Outcome
• Viral Matrix Proteins (chemistry)
• gp100 Melanoma Antigen