Search

Reports on traditional boundaries among basic research, clinical research and patient-oriented research which are yielding to a single, continuous, bidirectional spectrum commonly termed "translational research" or "translational medicine". Definition of guidelines for drug development or for the identification and validation of clinically relevant biomarker; Experimental nonhuman and nonclinical studies conducted with the intent of developing principles for the discovery of new therapeutic strategies; Basic science studies that define the biological effects of therapeutics in humans.

Immunological memory is thought to depend on a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells. These cells, specific to multiple viral and self-tumor antigens, were found within a CD45RO?, CCR7+, CD45RA+, CD62L+, CD27+, CD28+ and IL-7R?+ T cell compartment characteristic of naive T cells. However, they expressed large amounts of CD95, IL-2R?, CXCR3, and LFA-1, and showed numerous functional attributes distinctive of memory cells. Compared with known memory populations, these lymphocytes had increased proliferative capacity and more efficiently reconstituted immunodeficient hosts, and they mediated superior antitumor responses in a humanized mouse model. The identification of a human stem cell-like memory T cell population is of direct relevance to the design of vaccines and T cell therapies. [ABSTRACT FROM AUTHOR]

'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer, but their clinical efficacy has yet to be demonstrated. We sought to enhance the immunogenicity of a nucleic acid vaccine by making it 'self-replicating'. We accomplished this by using a gene encoding an RNA replicase polyprotein derived from the Semliki forest virus, in combination with a model antigen. A single intramuscular injection of a selfreplicating RNA immunogen elicited antigen-specific antibody and CD8[sup +] T-cell responses at doses as low as 0.1 µg. Pre-immunization with a self-replicating RNA vector protected mice from tumor challenge, and therapeutic immunization prolonged the survival of mice with established tumors. The self-replicating RNA vectors did not mediate the production of substantially more model antigen than a conventional DNA vaccine did in vitro. However, the enhanced efficacy in vivo correlated with a caspase-dependent apoptotic death in transfected cells. This death facilitated the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. Naked, non-infectious, self-replicating RNA may be an excellent candidate for the development of new cancer vaccines. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article ""Cancer Vaccines: Pessimism in Check," that was previously published in the journal "Nature Medicine."