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

Journal of Translational Medicine

Massimo Guidoboni¹  Livia Turci²  Antonino Romeo⁴  Elisabetta Parisi⁴  Angela Riccobon¹  Serena Cassan¹  Valentina Soldati¹  Elena Pancisi¹  Valentina Ancarani¹  Anna Maria Granato¹  Laura Fiammenghi¹  Massimiliano Petrini¹  Oriana Nanni³  Linda Valmorri³  Giorgia Gentili³  Ruggero Ridolfi¹  Laura Ridolfi¹  Francesco de Rosa¹ 

[1] Immunotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei, Tumori (IRST) IRCCS, Meldola, FC, Italy;Center for Biological Resources, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, MeldolaFC, Italy;Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy;Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

关键词: Dendritic cell;    Radiotherapy;    Melanoma;    Vaccine;   

Others  :  1148680
DOI  :  10.1186/1479-5876-12-209

 received in 2014-04-10, accepted in 2014-07-02,  发布年份 2014

【 摘 要 】

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;

(4.) neither 1 nor 2.

At least six patients eligible for treatment will be enrolled per arm. Daily 3 MU IL-2 will be administered subcutaneously for 5 days starting from the second day after each vaccine dose. Serial DTH testing and blood sampling to evaluate treatment-induced immune response will be performed. Objective response will be evaluated according to immune-related response criteria (irRC).

Discussion

Based upon the emerging role of radiotherapy as an immunologic modifier, we designed a randomized phase II trial adding radiotherapy and/or preleukapheresis IFN-α to our DC vaccine in metastatic melanoma patients. Our aim was to find the best combination of complementary interventions to enhance anti-tumor response induced by DC vaccination, which could ultimately lead to better survival and milder toxicity.

【 授权许可】

   
2014 de Rosa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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