Clinical Benefit of Allogeneic Melanoma Cell Lysate–Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

• Published in: Clinical cancer research 2009-12, Vol.15 (24), p.7726-7736
• Main Authors: HAN CHONG TOH, WANG, Who-Whong, KIAN FONG FOO, SIMON ONG, WEN HSIN KOO, ZOCCA, Mai-Britt, CLAESSON, Mogens H, WHAY KUANG CHIA, KVISTBORG, Pia, LI SUN, TEO, Kelly, YEE PENG PHOON, SOE, Yatanar, SZE HUEY TAN, SIEW WAN HEE
• Format: Article
• Language: English
• Subjects: allogeneic lysate; Antineoplastic agents; Biological and medical sciences; dendritic cells; Dermatology; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; Pharmacology. Drug treatments; protein array; regulatory T cells; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-1537

Purpose: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)–pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. Experimental Design: DCs were cultured from peripheral blood mononuclear cells (PBMC), pulsed with the allogeneic MCL, and matured using cytokines that achieved high CD83- and CCR7-expressing DCs. Each patient received up to 10 intradermal vaccinations (3-5 × 10 6 cells per dose) at biweekly intervals. Results: Twenty patients received a total of 161 vaccinations. Treatment was well tolerated and quality of life measurements did not vary much across time. One patient experienced partial response [5%; 95% confidence interval (CI), 1-24%] and seven achieved stable disease (35%; 95% CI, 18-57%), one of whom also achieved late tumor regression, yielding a clinical benefit response rate of 40% (95% CI, 22-61%). Although overall median progression-free survival was 2.4 months (95% CI, 1.9-4.1 months), five patients (25%) experienced prolonged progression-free survival (>6 months), two of whom (10%) remain progression-free for >27 and >37 months, respectively. This result is particularly meaningful as all patients had progressive disease before treatment. Overall, DC vaccination was associated with a serial decline in regulatory T cells. Using an antibody array, we characterized plasma protein profiles in responding patients that may correlate with vaccine activity and report a prevaccination protein signature distinguishing responders from nonresponders. Conclusion: This phase II vaccine study using mature, MCL-pulsed DCs has shown promising results and warrants further evaluation in a prospective randomized setting. (Clin Cancer Res 2009;15(24):7726–36)