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Neuroectodermal Tumors, Primitive

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Vaccines

Immunomodulating Agents

Vaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from untreated monocytes

Vaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from monocytes transfected with control siRNA

Vaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from monocytes transfected with siRNA targeting the three inducible immunoproteasome subunits

The safety and toxicity of vaccination with tumor antigen RNA-transfected dendritic cells (DC), derived from either untransfected or siRNA-transfected monocytes, will be evaluated in subjects with metastatic melanoma. Subjects will undergo leukapheresis and monocytes will be isolated. These monocytes will then be left untreated (Study Arm A) or transfected with either control siRNA (Study Arm B) or siRNA targeting immunoproteasome subunits LMP2, LMP7, and MECL1 (Study Arm C), then differentiated into DC in vitro . After the induction of maturation, these DC will be transfected with RNA encoding defined melanoma antigens MART, MAGE-3, tyrosinase, and gp100. These RNA-transfected autologous DC will be cryopreserved, then used to vaccinate subjects with metastatic melanoma, each of whom will receive a total of six intradermal (ID) injections using 1x10e7 DC at each cycle, administered weekly.

Proteasome siRNA and tumor antigen RNA-transfected dendritic cells

Scott K Pruitt, MD, PhD

Transfection with siRNA targeting the immunoproteasome alters proteasome-mediated antigen processing by the dendritic cell, generating TAA-derived peptides that we hypothesize, based on preclinical results, will induce enhanced anti-melanoma immune responses. This phase I study, open to subjects with metastatic melanoma, will assess the safety of vaccination with melanoma tumor associated antigen-encoding RNA-transfected mature dendritic cells derived from monocytes that have been either untreated, transfected with control siRNA, or transfected with siRNA targeting the inducible immunoproteasome beta subunits LMP2, LMP7, and MECL1. A combination of RNAs encoding melanoma tumor associated antigens MART-1, tyrosinase, gp100, and MAGE-3 will be utilized for dendritic cell transfection. The vaccine will be administered by intradermal injection in the extremities. Clinical and laboratory toxicities will be characterized for each study arm. As a secondary objective, this phase I study will also assess the anti-melanoma immune responses, as well as clinical responses, induced by vaccination with this dendritic cell-based product.

Immunotherapy of Melanoma With Tumor Antigen RNA and Small Inhibitory RNA Transfected Autologous Dendritic Cells

Phase I Study of Active Immunotherapy of Metastatic Melanoma With Mature Autologous Dendritic Cells Transfected With Tumor Antigen RNA and Small Inhibitory RNAs to Alter Proteasomal Antigen Processing

Scott Pruitt

Associate Professor of Surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immunotherapy of Melanoma With Tumor Antigen RNA and Small Inhibitory RNA Transfected Autologous Dendritic Cells	NCT00672542	Metastatic Mela... Absence of CNS ...	Proteasome siRN...	18 Years -	Duke University
Immunotherapy of Melanoma With Tumor Antigen RNA and Small Inhibitory RNA Transfected Autologous Dendritic Cells	NCT00672542	Metastatic Mela... Absence of CNS ...	Proteasome siRN...	18 Years -	Duke University

Spots Global Cancer Trial Database for absence of cns metastases