Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.
The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.
Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.
A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.
In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).
"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.
Dr. Batchu and his colleagues reported that they had no conflicts of interest.