Phase 1 Trial of Wilms Tumor 1 (WT1) Peptide Vaccine and Gemcitabine Combination Therapy in Patients With Advanced Pancreatic or Biliary Tract Cancer

Abstract

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.

Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response

“…This was also observed after peptide vaccination in renal cell cancer patients (16). In addition, some patients experienced persisting swelling and ulceration of the skin at the injection site, similar to what is found for the tetanus vaccine, hepatitis B, and BCG vaccine (17,18) and other vaccines with Montanide (19)(20)(21). Further optimization of clinical response rates and/or reduction of side effects may be achieved by using alternative adjuvants replacing Montanide, careful doseresponse studies, and by combination of vaccination with imiquimod on the lesion.…”

The importance of correctly timing cancer immunotherapy

“…Similarly, gemcitabine could also increase the percentage of circulating monocytes, M1, and DCs [52,114]. Administration of this chemotherapy alone or in poly-chemotherapy regimens before immunotherapy may also enhance the clinical efficacy through these mechanisms [62,114,115].…”

Treatment with Chemotherapy and Dendritic Cells Pulsed with Multiple Wilms' Tumor 1 (WT1)–Specific MHC Class I/II–Restricted Epitopes for Pancreatic Cancer

“…10,11), and has been found to be both oncogenic during tumorigenesis (12) and immunogenic (13)(14)(15). Therefore, other groups and our laboratory have performed clinical studies investigating the efficacy of immunotherapies targeting WT1 using a MHC-I restricted peptide for patients with PDA (16,17). Recently, MHC class II (MHC-II) epitopes derived from WT1 have been made available for use in clinical trials (18,19).…”