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Perspectives Targeting dendritic cells — why bother ?
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kreutz, Martin Tacken, Paul Figdor, Carl G. |
| Copyright Year | 2013 |
| Abstract | Classic vaccines are among the most cost-effective public health interventions and provide a good example of effective immunotherapy. Their development has been one of trial and error spanning several centuries. Initially, farm animals and humans were inoculated with serous fluid from infected individuals to protect against infectious diseases. In the late 18th century, Jenner published a relatively safe immunization strategy, using cowpox to provide cross-immunity against smallpox in humans. Many governments worldwide rapidly implemented this procedure, acknowledging its potential to reduce the devastating effect of epidemics on the general population. In the 19th century, Pasteur generated artificially weakened pathogens and used them for vaccination against rabies and anthrax. Adjuvants were introduced in the 20th century by Ramon, who showed that vaccine efficacy was enhanced by the addition of substances such as bread crumbs, tapioca, starch oil, or saponin. Aluminum salts (alum) were among the first adjuvants to be applied and remain, to date, the most common adjuvant in prophylactic vaccines. For decades, alum was the only adjuvant licensed for human use, but its mechanisms of action are only now being understood. Despite successful application in many vaccines, the use of alum is limited to vaccines aiming to induce Th2-type immunity. These classic prophylactic vaccines focus mainly on the induction of longlived T-helper cell–dependent IgG responses. However, therapeutic vaccines for treatment of chronic infections and cancer require strong proinflammatory CD41 and CD81 T-cell responses. Advanced knowledge in the molecular and cellular mechanisms underlying effective immune responses has revolutionized vaccine development over the past decades. Last year’s Nobel Laureates Beutler, Hoffman, and Steinman made seminal contributions to the two pillars that form the basis of present-day rational vaccine design. Together, with important work by Medzhitov and Janeway, Beutler and Hoffman discovered how Toll-like receptors (TLRs) activate immune cells. This resulted in the broad range of TLR agonists that are currently explored in clinical trials. Steinman discovered the dendritic cell (DC), the key antigen presenting cell (APC) orchestrating adaptive immune responses that is particularly important in effectuating potent CD41 and CD81 T-cell responses. Steinman’s work formed the basis for cellular vaccines, such as the licensed Sipuleucel-T, and for vaccines specifically targeting antigens to DC surface receptors. Although it seems logical in vaccine design to focus on DCs as the most potent APCs, the identification of various subsets complicate the choice. Immunologists are vigorously attempting to unravel the biological properties of these subsets to learn how to best reach and activate them, and thus to improve vaccine design. In this Perspective, we discuss recent findings and provide guiding principles for the development of novel vaccine strategies. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/121/15/2836.full.pdf?sso-checked=true |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
