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Discovery In Nature Elucidates Immune Cells In Skin And Supports Novel Vaccine Approach

March 1, 2012

Research shows for the first time that resident memory T cells prevalent in the skin are more protective in fighting infection than central memory T cells in the bloodstream

TREM Rx, Inc., a biotechnology company with a proprietary technology platform for novel vaccines delivered to the skin, announced today the results of an in vivo preclinical study that shows, for the first time, that powerful cells of the immune system called TREMs (T Resident Effector Memory cells) prevalent in the skin can mediate a protective immune response that is far stronger than memory T cells that circulate in the bloodstream. The study was published in today’s online edition of Nature and was led by TREM Rx scientific founder, Dr. Thomas S. Kupper, the Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School, and chair of Dermatology at Brigham and Women’s Hospital and the Dana Farber Cancer Institute.

This research and previous work by Dr. Kupper’s group demonstrated that a stronger generalized T cell immune response, and in particular a more robust TREM response, can be produced by delivering a viral vaccine vector to the upper skin tissues, as compared to below the skin or into the muscle. This new research reveals why novel vaccines administered to upper layers of the skin in preclinical models have demonstrably better preventative and therapeutic efficacy over conventional vaccine injection into the muscles or bloodstream. TREM Rx has exclusive rights to this vaccine-relevant intellectual property as the basis for the company’s proprietary technology platform for developing novel vaccines.

“Conventional vaccines are typically focused on optimizing the B cell arm of the immune system to create disease-fighting antibodies. In contrast, this study shows that a more effective path to immunity may be to engage this newly discovered part of the T cell arm of the immune system through a population of powerful immune cells that we now know reside in the skin, lung, gut, and other epithelial tissues,” said Thomas S. Kupper, MD, senior author of the Nature paper.

“Putting this research in historical context, it helps explain the uniquely powerful efficacy of the first successful vaccine developed for smallpox by Jenner in 1796,” said Kupper. “Syringes had not yet been invented, so Jenner administered the first vaccine by disrupting the upper layers of skin with a specialized needle, a process similar to how the vaccinia virus was delivered in our study. It is worth remembering that the smallpox vaccine remains the most effective vaccine in the history of medicine, resulting in the elimination of smallpox in human populations.”

In the preclinical study in Nature, vaccinia virus delivered to the skin was found to rapidly recruit viral-specific T cells, called TREMs (T Resident Effector Memory cells), not just to the infected site, but also to all areas of the skin. These TREMs remained in skin, and provided rapid and effective protection against a second infection from the same virus. While skin was used as a model system in the study, the results are relevant to epithelial cells in the lungs, GI tract, and other epithelial tissues that are sites of viral entry to the body.

The findings of this study challenge immunological dogma by suggesting that the most important elements of T cell memory and immunity to infectious diseases may reside in skin and other epithelial tissues mediated by TREMs, rather than by circulating T or B cells in the blood. With regard to the impact on vaccine design and delivery, the study suggests that vaccines to generate TREM can be optimized by delivery through epithelial tissues, for a potentially more effective immune response than is achieved with conventional vaccine injection.

“This groundbreaking research provides a major opportunity to develop a new class of vaccines with improved preventative and therapeutic efficacy that can potentially have a major impact on human health,” said Eric Stromquist, president of TREM Rx. “We are committed to translating this new understanding of protective immunity to the design of novel vaccines for a wide range of applications, including important infectious diseases and cancers.”

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