Baylor Research Institute (BRI): Improving the Efficacy of Dendritic Cell Vaccines

	A CHR Trial Investigation Outcomes of Exercise Training
	Altered CD8+ T Cell Compartment in SLE Patients
	A Systems Biology Approach for Pediatric and Adult Autoimmune Diseases
	Genome-Wide Profiling of Antigen-Specific Immunoreactivity in Multiple Sclerosis (A Pilot Project to ‘A Systems Biology Approach for Pediatric and Adult Autoimmune Diseases’; PI: Virginia Pascual, MD)
	A Systems Biology Approach to Islet Antigen Immunoreactivity Profiling in T1D
	Biology and Diagnosis of HNPCC
	Blood Transcriptional Biomarker Profiles for Category B Pathogens
	Center for Lupus Research
	Colon Cancer Prevention Program Project
	Development of Neonatal Oxygen Therapy Information System to Support Oximetry Targets in Newborn Intensive Care Units
	Diversification of cytotoxic effector cells via LPS-activated DCs
	Effect of S-adenosylmethionine on Blood Homocysteine
	Functional MR in Ischemic Cardiomyopathy
	Harnessing Human DC Subsets for Improved Mucosal Vaccines
	Supplement #1 to ‘Harnessing Human DC Subsets for Improved Mucosal Vaccines’
	Supplement #2 to ‘Harnessing Human DC Subsets for Improved Mucosal Vaccines’
	Supplement #3 to ‘Harnessing Human DC Subsets for Improved Mucosal Vaccines’
	Immunotherapeutic HPV Cancer Vaccines that Target Langerhans Cells
	Improving the Efficacy of Dendritic Cell Vaccines
	JC Virus and Tumor Formation in the Human Colon
	Monitoring Blood Genome Activity during Pregnancy
	Novel Dendritic Cell-Based HIV Vaccines
	Rural Hospital Collaborative for Excellence Using IT
	Towards an HCV Vaccine
	Transcriptional Signatures for Diagnosis of Different Spectra of Mycobacterium tuberculosis Infection and Characterization of the Immune Response during Latency or Active Disease
	Use of Microarrays to Understand Systemic Arthritis
	Vaccination with IL-15 DC to Generate Melanoma-Specific Protective Memory T Cells

Improving the Efficacy of Dendritic Cell Vaccines

Grant Number: CA84512 PI: Jacques Banchereau, PhD Funding Organization: National Cancer Institute Project Start: June 1, 2006 Project End: April 30, 2014 Abstract: Active immunization with dendritic cells (DCs) is an important new treatment modality in cancer. Vaccination of HLA-A*201 patients with metastatic melanoma with dendritic cells (DCs) derived from CD34+ hematopoietic cell progenitor cells (CD34+HPCs) loaded with melanoma peptide antigens, KLH and flu peptide resulted in the induction of CD8+ T cell immunity to melanoma peptides and some clinical benefit. Immunity was measured by the production of interferon-gamma in the presence of melanoma peptides and control antigens by CD8+ T cells obtained from blood. T cell immunity correlated with early clinical outcome and survival. Patients who progressed early had either no T cell immunity or transient T cell immunity to DC vaccination. There may be several reasons for the absence of DC-induced CD8+ T cell immunity in these patients including: the inability of DCs to prime T cells against tumor antigens, the presence of tumor specific tolerance induced by host suppressor lymphocytes, and an insufficient anti-melanoma T cell repertoire. AIM 1 will determine whether pre-treatment of patients with stage IV melanoma with CPA improves the immune and clinical response after DC vaccination. We will carry out a phase I/II randomized clinical trial in patients with stage IV melanoma who will receive either placebo or CPA (500mg/m2) followed by vaccination with CD34-DCs pulsed with melanoma peptides and KLH. As a control, a separate aliquot of DCs will be pulsed with HIV peptides as neoantigens that will be mixed with the peptide-loaded DCs and administered at the same time. The primary outcome is the induction of melanoma-specific CD8+T cell immunity. The secondary outcome is the rate of objective clinical responses. Tertiary outcomes are: reduction of regulatory/suppressor CD4+T cells (AIM 2) and priming of HIV-specific CD8+T cells (AIM 3).