Vaccination of Urological Cancer Patients With WT1 Peptide‐Pulsed Dendritic Cells in Combination With Molecular Targeted Therapy or Conventional Chemotherapy Induces Immunological and Clinical Responses

Abstract

The prognosis of metastatic or relapsed renal cell carcinoma (RCC) or bladder cancer (BC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with WT1 peptide-loaded dendritic cells (DCs) and OK-432 adjuvant combined with molecular targeted therapy or conventional chemotherapy. Five eligible patients with metastatic or relapsed RCC and five eligible patients with BC were enrolled. No severe adverse events related to a vaccination were observed. Seven patients with RCC or non-muscle invasive BC had durable stable disease and three other patients had disease progression after DC vaccination. DC vaccination augmented WT1 specific immunity and the reduction of regulatory T cells which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a molecular targeted therapy or a conventional chemotherapy is safe and feasible for patients in advanced stage of RCC or BC.

Phase I/II Pilot Study of Wilms' Tumor 1 Peptide‐Pulsed Dendritic Cell Vaccination Combined With Conventional Chemotherapy in Patients With Head and Neck Cancer

“…DCs were prepared as described previously . Briefly, leukapheresis was carried out 3–4 weeks after the previous chemotherapy when peripheral WBC count, hemoglobin concentration and platelet count were above 2000 cells/μL, 9.0 g/dL, and 90 000 cells/μL, respectively.…”

“…The vaccination regimen has been described previously . Briefly, cryo‐preserved DCs were thawed, washed with physiological saline (Otsuka Pharmaceutical, Tokyo, Japan) containing 10% dextran (10 mL, Otsuka Pharmaceutical) once and then washed with physiological saline (10 mL) twice to get rid of remaining DMSO and human albumin.…”

“…The cultured cells were examined for the presence of WT1‐specific T‐cells by an IFNɤ enzyme‐linked immunospot (ELISPOT) assay kit purchased from Invitogen/Thermo Fisher Scientific following the procedure recommended by the manufacturer . Briefly, an aliquot of PBMNCs suspended in RPMI1640 supplemented with 5% human AB serum was added to a well of an nitrocellulose plate pre‐coated with anti‐human IFNɤ moAb.…”

“…The cultured cells were stained with HLA‐A24 WT1 tetramer or HLA‐A24 HIV tetramer together with PE‐conjugated anti‐CD3 and PerCP‐conjugated anti‐CD8 antibodies according to the method recommended by the manufacturer (MBL, Nagoya, Japan) . Cells were then washed extensively with cold FACS buffer and analyzed immediately by FACScan using CellQuest software (Becton Dickinson Japan).…”

“…The cultured cells were incubated with WT1 or HIV peptide (10 μg/mL each) in the presence of FITC‐conjugated CD107a moAb (MBL) or FITC‐conjugated mouse IgG1 isotype control moAb and monensin (MBL) in PRMI1640 supplemented with 5% AB serum. After 4‐h incubation, cells were washed with FACS buffer, stained with PE‐conjugated CD8 moAb and analyzed by FACS . This assay was performed additionally for the patients whose residual PBMNCs were available.…”