Long-term administration of Wilms tumor-1 peptide vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites.

The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1-2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4-8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

Camouflage makeup improves quality of life in cancer patients with treatment-related skin changes.

BACKGROUND: Cancer treatment causes various skin appearance changes, which affect quality of life (QoL) in patients with cancer. We examined whether camouflage makeup improves QoL in these patients. METHODS: Skindex-16 and visual analogue scale scores of 39 female patients with cancer treatment-related skin changes were compared before and 2-3 months after self-administration of camouflage makeup. RESULTS: Camouflage makeup was able to conceal almost all skin changes, improving QoL scores regardless of age, diagnosis, and site of skin changes. Use frequency was significantly higher in patients with skin changes on exposed sites compared with patients with unexposed sites. CONCLUSIONS: Even though the patients applied the makeup only when required, they were satisfied with its effect, which improved their QoL. Moreover, the makeup had a positive effect even in patients with changes in unexposed sites, suggesting that clinicians can recommend camouflage makeup to all patients to improve QoL.

Real-time in vivo cellular imaging of graft-versus-host disease and its reaction to immunomodulatory reagents.

Visualizing the in vivo dynamics of individual donor cells after allogeneic hematopoietic stem cell transplantation (HSCT) will enable deeper understanding of the process of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). In this study, using non-invasive in vivo fluorescence imaging of the ear pinna, we successfully visualized green fluorescent protein (GFP) donor cells at the single cell level in the skin. This imaging model enabled visualization of the movement of GFP cells into blood vessels in real time after allogeneic HSCT. At day 1, a few donor cells were detected, and the movement of donor cells in blood vessels was readily observed at day 4. Early donor cell infiltration into non-lymphoid tissue was increased by treatment with croton oil, as an inflammatory reagent. Treatment with dexamethasone, as an anti-inflammatory reagent, suppressed donor cell infiltration. The in vivo cellular fluorescence imaging model described here is a very useful tool for monitoring individual donor cells in real-time and for exploring immunomodulatory reagents for allogeneic HSCT, as well as for understanding the mechanism of GVHD.

Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer.

An open-labeled, dose-escalation phase 1 trial of Wilms tumor 1 (WT1) vaccine and gemcitabine (GEM) combination therapy for patients with advanced pancreatic cancer or biliary tract cancer was performed. The primary end point was evaluation of toxicity, safety, and optimal immunologic dose of vaccine. Human leukocyte antigen (HLA)-A 0201, HLA-A 0206, and/or HLA-A 2402-positive patients with inoperable advanced pancreatic or biliary tract cancer who had not previously been treated with GEM were eligible for this study. Six doses of GEM and 4 doses of WT1 peptide (1 or 3 mg) emulsified in Montanide adjuvant were administered over 2 months. Twenty-five patients (13 male and 12 female) were enrolled. Nine patients had inoperable advanced pancreatic cancer, 8 had gallbladder cancer, 4 had intrahepatic, and 4 had extrahepatic bile duct cancer. The adverse events were comparable to those with GEM alone. Delayed-type hypersensitivity test was positive after vaccination in 2 patients, and WT1-specific T cells in peptide-stimulated culture were detected by tetramer assay in 59% (13 of 22) of patients. The disease control rate at 2 months was 89% for pancreatic cancer and 50% for biliary tract cancer. With a median follow-up time of 259 days, the median survival time for biliary tract cancer was 288 days, and that for pancreatic cancer was 259 days. Although objective clinical efficacy was not apparent, the safety of WT1 vaccine and GEM combination therapy was confirmed in this study.