Second-Generation Therapeutic DNA Lymphoma Vaccines
Abstract
The idea of genetic vaccination originated from the observation that injection of DNA into living animals resulted in expression of gene products in vivo. Preclinical studies revealed that genetic immunization induced both antigen-specific antibody and cytotoxic T lymphocyte. Early human trials of DNA vaccines have been mainly focused on infectious disease, and vaccines against malignant disease have activated anti-tumor immunity in cancer patients and extended remission. Compared with proteins or peptides, genetic vaccines are highly appealing. The antigen synthesized in host cellular machinery is naturally processed by antigen presenting cells (APC) to release all potential antigenic epitopes for priming antigen-specific immunity, avoiding HLA restriction that is absolutely required for peptide vaccine. Moreover, simplicity in large-scale production and purification makes DNA vaccines more attractive than protein. However, the goal of using DNA vaccines as a clinical therapy has not yet been achieved. The major obstacle preventing general use of DNA vaccines on patients is that the plasmid DNA, especially those encoding non-immunogenic, tumor-associated self-antigens, is relatively weak in inducing immunity. Developing an efficient strategy to enhance immunogenicity is therefore vital for translational vaccine development. An immune adjuvant is a substance that is used to improve the efficiency of vaccine. It is usually designed to boost a critical step in the development of adaptive immunity. The downstream effects of adjuvant can be linked to enhancing the function of dendritic cells (DC) in antigen uptake and presentation. Examples include chemokines for DC recruitment, Toll-like receptor (TLR) agonists for DC maturation, and CD40 ligand and interferon-alpha which enhance Tcell activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2011
- Accession Number
- ADA544927
Entities
People
- Larry Kwak
Organizations
- The University of Texas MD Anderson Cancer Center