Site Search     
 
  Dendritic Cell Based Cancer Vaccines
  Genes of Health: Signature of Health and Disease in Humans
  Human Dendritic Cell Biology
  Humouse: An In Vivo Model of the Human Immune System
  Infectious Diseases
  Understanding of Systemic Lupus Erythematosus
  Current BIIR Grants
  Key BIIR Papers
Key BIIR Papers
Paczesny, S., J. Banchereau, K.M. Wittkowski, G. Saracino, J. Fay, and A.K. Palucka. 2004. Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. J Exp Med 199:1503-1511.

Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse. We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34-dendritic cells (DCs) leads to expansion of melanoma-specific interferon gamma-producing CD8+ T cells in the blood. Here, we show in 9 out of 12 analyzed patients the expansion of cytolytic CD8+ T cell precursors specific for melanoma differentiation antigens. These precursors yield, upon single restimulation with melanoma peptide-pulsed DCs, cytotoxic T lymphocytes (CTLs) able to kill melanoma cells. Melanoma-specific CTLs can be grown in vitro and can be detected in three assays: (a) melanoma tetramer binding, (b) killing of melanoma peptide-pulsed T2 cells, and (c) killing of HLA-A*0201 melanoma cells. The cytolytic activity of expanded CTLs correlates with the frequency of melanoma tetramer binding CD8+ T cells. Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen-expressing targets. These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.