NCI Funded Research Portfolio - Z01 BC 010952 Abstract

Z01 BC 010952 (Z01)
Title	Cytokines to control the immune response in cancer vaccine development
Institution	NCI, Bethesda, MD
Principal Investigator	Sabzevari, Helen	NCI Program Director	N/A
Cancer Activity	N/A	Division	CCR
Funded Amount	$256,705	Project Dates	10/01/2007 - N/A
Fiscal Year	2008	Project Type	Intramural
Research Topics (SICs) w/ Percent Relevance		Cancer Types (Disease Sites) w/ Percent Relevance
Biological Response Modifiers (100.0%) Breast Cancer - Treatment (20.0%) Digestive Diseases (20.0%)		Breast Cancer (20.0%) Colon/Rectum (20.0%) Genital System - Male Other (20.0%) Lung (10.0%) Prostate (20.0%)
Common Scientific Outline
Systemic Therapies - Discovery and Development Vaccines
Abstract	Interleukin-2 (IL-2)/anti-IL-2 antibody complex enhances vaccine-mediated antigen-specific CD8+ T-cell responses and increases the ratio of effector/memory CD8+ T cells to T regulatory cells (Treg cells). IL-2 is well described as a cytokine with two markedly distinct functionalities: as a necessary signal during CD4+ and CD8+ T cell activation/expansion and as an essential cytokine for the maintenance of CD4+CD25+FoxP3+ T cells (T regulatory cells) during homeostasis. In this study we demonstrate for the first time that, compared with the use of IL-2 alone, a complex of IL-2 and anti-IL-2 Ab (IL-2 complex) enhances the effectiveness of a viral vaccine in a mouse model with known Ag specificity. IL-2 complex led to an increase in the number of antigen-specific effector/memory CD8+ T cells, cytokine production, and cytotoxic T lymphocyte (CTL) lysis following antigen-specific restimulation in a vaccination setting. Our results further demonstrate that this effect is temporary and declines over the course of a few days after the IL-2 complex treatment cycle. Moreover, in contrast to the use of IL-2 alone, IL-2 complex greatly increased the ratio of effector/memory CD8+ T cells to Treg cells. This phenomenon can thus potentially be used in the enhancement of immune responses to vaccination.