Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory and Winship Cancer Institute researchers have found.
The results were published this week in the journalÂ PLOS Pathogens.
The findings suggest imatinib, known commercially as Gleevec, or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cellsÂ in vitro, but provides information on how to dose imatinib for new clinical applications.
â€œWe think that low doses of imatinib are mimicking â€˜emergency hematopoiesis,â€™ a normal early response to infection,â€ says senior author Daniel Kalman, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine.
Imatinib, is an example of a â€œtargeted therapyâ€ against certain types of cancer. It blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.
Imatinib also inhibits normal forms of these enzymes that are found in healthy cells. Several pathogens â€“ both bacteria and viruses â€“ exploit these enzymes as they transit into, through, or out of human cells. Researchers have previously found that imatinib or related drugs can inhibit infection of cells by pathogens that are very different from each other, includingÂ tuberculosis bacteriaÂ andÂ Ebola virus. Read more
Emory Vaccine Center director Rafi Ahmed, is a co-author on a recent Science paper advocating a â€œHuman Vaccines Projectâ€. Wayne Koff, chief scientific officer of IAVI (International Aids Vaccine Initiative) is lead author and several other vaccine experts are co-authors.
The idea behind a â€œHuman Vaccine Projectâ€ is to combine efforts at developing vaccines for major (but very different) diseases such as influenza, dengue, HIV, hepatitis C, tuberculosis and malaria, with the rationale that what scientists working on those diseases have in common is the Ray Ban outlet challenge of working with the human immune system.
Technology has advanced to the point where whole genome-type approaches can be brought to bear on vaccine problems. The authors cite work by Bali Pulendranâ€™s laboratory on â€œsystems vaccinologyâ€ and their analysis of the yellow fever vaccine as an example.
One major puzzle confronting vaccine designers is to coax the immune system into producing broadly neutralizing antibodies against a rapidly mutating virus, whether it is Gafas Ray Ban outlet influenza or HIV. Our own Cynthia Derdeyn has been analyzing this problem through painstaking work following how the immune system pursues a twisting and turning HIV.
An interesting related tidbit:
There are hints that the reverse engineering of vaccines has taken a leap forward in the case of RSV (respiratory syncytial virus): Scientists at Scripps Research Institute have designed vaccine components by computer and have used them to provoke neutralizing antibodies in monkeys.
Also check out Mike Kingâ€™s feature in Emory Health on HIV vaccine research.