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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) The efficacy of therapeutic cancer vaccines in humans has in general been poor (1-3). An overall objective response rate of only 3.3% was observed in 1,306 vaccine treatments of cancer patients with advanced disease (3). This lack of success might reflect poor immunogenicity of the adopted tumor-associated antigens (TAA) as well as downmodulation of tumor-associated antigenicity in advanced tumors (4). Local and systemic suppression mediated by the growing tumor and its environment, including activation and stimulation of regulatory T lymphocytes (Treg), tolerogenic dendritic cells (DC), myeloid-derived suppressor cells, and angiogenic factors, can also counteract vaccine-based immunotherapy (5). In clinical trials that have used autologous DC-based vaccinations, differentiated and immunogenic DCs generated ex vivo from peripheral blood monocytes were pulsed or transfected with a variety of TAA. This approach might more effectively expose the immune system of the patient to immunogenic TAA, and because the DCs are already differentiated, may overcome the tolerogenic tumor environment in the patient. This view is supported by theoretical (4) as well as practical considerations. Preclinical s...

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.