The evolution of the axonal transport toolkit

Neurons are highly polarized cells that critically depend on long‐range, bidirectional transport between the cell body and synapse for their function. This continual and highly coordinated trafficking process, which takes place via the axon, has fascinated researchers since the early 20th century. Ramon y Cajal first proposed the existence of axonal trafficking of biological material after observing that dissociation of the axon from the cell body led to neuronal degeneration. Since these first indirect observations, the field has come a long way in its understanding of this fundamental process. However, these advances in our knowledge have been aided by breakthroughs in other scientific disciplines, as well as the parallel development of novel tools, techniques and model systems. In this review, we summarize the evolution of tools used to study axonal transport and discuss how their deployment has refined our understanding of this process. We also highlight innovative tools currently being developed and how their addition to the available axonal transport toolkit might help to address key outstanding questions

DNA fusion gene vaccines against cancer: from the laboratory to the clinic

Vaccination against target antigens expressed by cancer cells has now become a realistic goal. DNA vaccines provide a direct link between identification of genetic markers in tumors and vaccine formulation. Simplicity of manufacture facilitates construction of vaccines against disease subsets or even for individual patients. To engage an immune system that exists to fight pathogens, we have developed fusion gene vaccines encoding tumor antigens fused to pathogen-derived sequences. This strategy activates high levels of T-cell help, the key to induction and maintenance of effective immunity. We have dissected the immunogenic tetanus toxin to obtain specific sequences able to activate antibody, CD4+, or CD8+ T cells to attack selected fused tumor antigens. Principles established in preclinical models are now being tested in patients. So far, objective immune responses against idiotypic antigen of neoplastic B cells have been observed in patients with B-cell malignancies and in normal transplant donors. These responses provide a platform for testing physical methods to improve DNA delivery and strategies to boost responses. For cancer, demands are high, because vaccines have to activate powerful immunity against weak antigens, often in a setting of immune damage or tolerance. Vaccination strategies against cancer and against microbes are sharing knowledge and technology for mutual benefit