RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy

Authors:
Coughlin CM, Vance BA, Grupp SA and Vonderheide RH
In:
Source: Blood
Publication Date: (2004)
Issue: 103: 2046-2054
Research Area:
Immunotherapy / Hematology
Cells used in publication:
B cell, human
Species: human
Tissue Origin: blood
Dendritic cell (NHDC), human
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Experiment
Primary dendritic cells (DCs) and CD40-activated B cells were nucleofected with mRNA coding for GFP, the influenza-derived epitope FluMP, or the tumor rejection antigen MART-1, respectively. In addition, CD40-activated B cells were transfected with pooled mRNA from 3 neuroblastoma cell lines or with RNA prepared from autologous tumor. All APCs were able to induce cytotoxic T lymphocytes (CTLs) that secreted interferon-gamma and killed targets.
Abstract
Vaccination with antigen-presenting cells (APCs) engineered to mimic mechanisms of immune stimulation represents a promising approach for cancer immunotherapy. Dendritic cell vaccines have entered phase 3 testing in adult malignancies, but such vaccines in children have been limited. We demonstrate that CD40-activated B cells (CD40-B) transfected with RNA may serve as an alternative vaccine that can be generated from small blood volumes regardless of patient age. CD40-B from pediatric patients are efficient APCs and can be loaded with RNA as an antigenic payload, permitting simultaneous targeting of multiple antigenic epitopes without the necessity of HLA matching. For viral and tumor antigens, CD40-B/RNA technology induced cytotoxic T lymphocytes (CTLs) from adults and children, which could be identified with peptide/major histocompatibility complex (MHC) tetramers. These CTLs secreted interferon-gamma (IFN-gamma) and killed targets in an MHC-restricted fashion. For pooled neuroblastoma RNA and autologous neuroblastoma RNA, CTLs that lysed neuroblastoma cell lines, including CTLs specific against the widely expressed tumor-antigen survivin, were generated. These findings support a novel platform for tumor-specific vaccine or adoptive immunotherapies in pediatric malignancies.