Rush Hour Traffic: Directing T Cells to Tumor
Menée sur 37 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cette étude met en évidence des mécanismes par lesquels, à l'échelle systémique et dans la tumeur, le système immunitaire répond à une administration de sipuleucel-T
In 2010, the Food and Drug Administration approved sipuleucel-T for the treatment of asymptomatic or minimally symptomatic castration-resistant metastatic prostate cancer based on demonstration of an improvement in overall survival in a randomized phase III clinical trial (1), one of three recent positive large controlled vaccine trials in a variety of human cancers that show that specific T cells can be elicited by vaccination (2,3). Sipuleucel-T is a patient-specific cellular product that is prepared by culturing autologous peripheral blood mononuclear cells ex vivo with a recombinant human fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony stimulating factor (GM-CSF). The final infusion product is comprised of a mixture of cells, including antigen-presenting cells (APC), T cells, B cells, natural killer (NK) cells, and others. Although sipuleucel-T is categorized as autologous cellular immunotherapy, its postulated mechanism of action suggests that it is a form of therapeutic cancer vaccine. The PAP serves as the tumor-associated antigen and is likely taken up by APCs during the in vitro culture and processed and presented on their surface in the context of major histocompatibility complex molecules. GM-CSF presumably acts as an adjuvant to activate APCs to enhance antigen presentation to T cells. Following administration to the patients, the APCs expressing PAP-derived peptides induce PAP-specific T cells that in turn …
Journal of the National Cancer Institute , éditorial en libre accès, 2014