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 Journal Article
| Authors: | Banchereau, J.; Ueno, H.; Dhodapkar, M.; Connolly, J.; Finholt, J. P.; Klechevsky, E.; Blanch, J. P.; Johnston, D. A.; Palucka, A. K.; Fay, J. |
| Article Title: | 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-α. 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-γ in direct ELISPOT. Melanoma-peptide- specific recall memory CD8+ T cells able to secrete IFN-γ 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-α-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors. Copyright © 2005 by Lippincott Williams & Wilkins. |
| Keywords: | adult; cancer survival; clinical article; controlled study; treatment outcome; disease-free survival; middle aged; unclassified drug; clinical trial; interferon; cancer staging; cell proliferation; cd34 antigen; glycoprotein gp 100; melanoma; controlled clinical trial; dendritic cell; neoplasm proteins; peptide; time factors; stem cell; dendritic cells; immune response; antigens, neoplasm; gamma interferon; cancer vaccines; membrane glycoproteins; disease progression; tumor antigens; melanoma antigen 3; peptide fragments; vaccination; cytotoxic t lymphocyte; peptides; stem cells; melan a; hematopoietic stem cell; phase 1 clinical trial; monophenol monooxygenase; enzyme-linked immunosorbent assay; tumor vaccine; recombinant granulocyte colony stimulating factor; enzyme linked immunospot assay; memory cell; antigens, cd34; matrix protein; hla-a antigens; immunotherapy, adoptive; viral matrix proteins; hla antigen; recombinant granulocyte macrophage colony stimulating factor; interferon-alpha; keyhole limpet hemocyanin; recombinant alpha2b interferon; interferon type i; interferon type ii; influenza matrix peptide; influenza a virus; helper antigens; tumor vaccines; alanylalanylglycylisoleucylglycylisoleucyllysylthreonylvaline; glycylisoleucylleucylglycylphenylalanylvalylphenylalanylthreonylleucine; isoleucylmethionylaspartylglutamylvalylprolylphenylalanylserylvaline; phenylalanylleucyltryptophylgylcylprolylarginylalanylleucylvaline; tyrosylmethionylaspartylglycylthreonylmethionylserylglutamylvaline |
| Journal Title: | Journal of Immunotherapy |
| Volume: | 28 |
| Issue: | 5 |
| ISSN: | 1524-9557 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2005-10-01 |
| Start Page: | 505 |
| End Page: | 516 |
| Language: | English |
| PUBMED: | 16113607 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 72" - "Export Date: 24 October 2012" - "CODEN: JOIME" - "Source: Scopus" |
