Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodula
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Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-α in patients with metastatic melanoma: a randomised “proof-of-principle” phase II study Francesco de Rosa1†, Laura Ridolfi1*†, Ruggero Ridolfi1, Giorgia Gentili2, Linda Valmorri2, Oriana Nanni2, Massimiliano Petrini1, Laura Fiammenghi1, Anna Maria Granato1, Valentina Ancarani1, Elena Pancisi1, Valentina Soldati1, Serena Cassan1, Angela Riccobon1, Elisabetta Parisi3, Antonino Romeo3, Livia Turci4 and Massimo Guidoboni1
Abstract Background: Vaccination with dendritic cells (DC) loaded with tumor antigens elicits tumor-specific immune responses capable of killing cancer cells without inducing meaningful side-effects. Patients with advanced melanoma enrolled onto our phase II clinical studies have been treated with autologous DC loaded with autologous tumor lysate/homogenate matured with a cytokine cocktail, showing a clinical benefit (PR + SD) in 55.5% of evaluable cases to date. The beneficial effects of the vaccine were mainly restricted to patients who developed vaccine-specific immune response after treatment. However, immunological responses were only induced in about two-thirds of patients, and treatments aimed at improving immunological responsiveness to the vaccine are needed. Methods/Design: This is a phase II, “proof-of-principle”, randomized, open-label trial of vaccination with autologous DC loaded with tumor lysate or homogenate in metastatic melanoma patients combined with immunomodulating RT and/or preleukapheresis IFN-α. All patients will receive four bi-weekly doses of the vaccine during the induction phase and monthly doses thereafter for up to a maximum of 14 vaccinations or until confirmed progression. Patients will be randomized to receive: (1.) three daily doses of 8 Gy up to 12 Gy radiotherapy delivered to one non-index metastatic field between vaccine doses 1 and 2 and, optionally, between doses 7 and 8, using IMRT-IMAT techniques; (2.) daily 3 MU subcutaneous IFN-α for 7 days before leukapheresis; (3.) both 1 and 2; (Continued on next page)
* Correspondence: [email protected] † Equal contributors 1 Immunotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei, Tumori (IRST) IRCCS, Meldola, FC, Italy Full list of author information is available at the end of the article © 2014 de Rosa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
de Rosa et al. Journal of Translational Medicine 2014, 12:209 http://www.translational-medicine.com/content/12/
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