Novel Vectors for Dendritic Cell Transduction
Abstract
Dendritic cells (DCs) show promise for cancer immunotherapy due to their critical role in mediating immune response. Development of an optimal DC transduction protocol for tumor antigen presentation would represent a significant advancement in DC-based vaccination strategies. We are evaluating novel vector systems for dendritic cell transduction. Replicative RNA transcripts based on the alphavirus family are noninfectious vectors capable of directing cytoplasmic replication and high level transgene expression upon entry into the cell. We hypothesize that the augmented expression afforded by the replicative RNA system will effectively stimulate T cells. Further, we hypothesize that the cytopathic effects induced by these vectors will enhance the DC-based immune response as suggested by the 'danger' model. A second approach uses adenoviral vectors to targeted to CD40 on DCs via a bispecific antibody, which we anticipate will promote maturation of the DCs. The target antigen we will evaluate is carcinoembryonic antigen (CEA). Animals will be immunized with the genetically modified DCs and induction of anti-CEA immune responses will be measured. Tumor challenge and tumor therapy experiments will be performed using a syngeneic adenocarcinoma cell line which expresses human CEA (MC38-CEA-2), and toxicity will be monitored. Both nontransgenic and CEA-transgenic mouse models will be used.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA395592
Entities
People
- Theresa V. Strong
Organizations
- University of Alabama