Posts Tagged ‘research’

Understanding, improving body’s fight against pathogens

While they exist in small populations in humans, the large amounts of antibodies secreted by plasma cells make them key to the body’s immune system and its ability to defend itself against pathogens, such as bacteria and viruses. Proper maintenance of a pool of plasma cells is also critical for the establishment of lifelong immunity elicited by vaccination.

Dysregulation of plasma cell production and maintenance could lead to autoimmune diseases and multiple myeloma. Autoimmune diseases occur when the immune system does not distinguish between healthy tissue and antigens, which are found in pathogens. This results in expansion of plasma cells which produce excessive amounts of antibodies leading to destruction of one’s own healthy tissue. The discoveries by scientists in BTI’s Immunology Group have improved understanding of the mechanism by which plasma cells are developed from a major class of white blood cells called B cells.

For the first time, the molecule DOK3 was found to play an important role in formation of plasma cells. While calcium signalling typically controls a wide range of cellular processes that allow cells to adapt to changing environments, it was found to inhibit the expression of the membrane proteins essential for plasma cell formation. These membrane proteins include PDL1 and PDL2, and represent some of the key targets for the development of immunotherapy by pharmaceutical companies. DOK3 was able to promote the production of plasma cells by reducing the effects of calcium signalling on these membrane proteins. The absence of DOK3 would thus result in defective plasma cell formation.

In another study, BTI scientists discovered the importance of SHP1 signalling to the long term survival of plasma cells. While the molecule SHP1 has a proven role in prevention of autoimmune diseases, it was found that the absence of SHP1 would result in the failure of plasma cells to migrate from the spleen where they are generated to the bone marrow, a survival niche where they are able to survive for much longer periods. This could result in a reduction of the body’s immune response and thus, an increased susceptibility to infections and diseases. The scientists in this study also successfully rectified the defective immune response caused by an absence of SHP1 by applying antibody injections, which might advance the development of therapeutics. On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma where the accumulation of cancerous plasma cells in the bone marrow survival niches is undesirable.

Findings hold potential for improved treatment

The discovery of these new targets for modulating the antibody response allows the development of novel therapeutic strategies for patients with autoimmune diseases and cancer.Understanding the mechanism that governs plasma cell differentiation is also critical for the optimal design of vaccines and adjuvants, which are added to vaccines to boost the body’s immune response.

Prof Lam Kong Peng, Executive Director of BTI, said, “These findings allow better understanding of plasma cells and their role in the immune system. The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma, but also impacts the development of immunological agents for combating infections.”

source : http://www.sciencedaily.com/releases/2014/09/140902115036.htm

Potential method to better control lung cancer using radiotherapy

Standard treatment for locally advanced non-small cell lung cancer is a combination of radiotherapy and chemotherapy. Traditionally this is planned in a one-size-fits-all manner but the radiation dose may not always be enough to stop tumor growth.

The potential to increase the radiation dose to the cancerous tissue varies between patients and depends on the size and location of the tumor in relation to sensitive organs such as the spinal cord and lungs. Now researchers at The University of Manchester and The Christie NHS Foundation Trust — both part of the Manchester Cancer Research Centre — have looked at ways to personalize and increase the dose to the tumor while minimizing the effect on healthy tissue.

Dr Corinne Faivre-Finn, researcher at The University of Manchester and Honorary Consultant at The Christie, who led the study, said: “Current standard options for the treatment of non-small cell lung cancer are associated with poor survival. We wanted to see if more advanced methods of planning and delivering radiotherapy treatment could potentially allow an increase in radiation dose.”

The group used data from 20 lung cancer patients to investigate whether a newer radiotherapy technique — intensity modulated radiotherapy (IMRT) — could potentially be used to increase the radiation dose to lung tumors, without harming healthy organs.

Their treatment planning methods ensured a safe radiation dose was delivered to the surrounding organs at risk. In an article recently published in the journal Clinical Oncology, they show that IMRT allowed an increase in radiation dose for non-small cell lung cancer.

“Our exploratory study suggests that using IMRT can allow radiation dose to be increased: calculations indicate that this could yield a 10% improvement in tumor control. We are starting a new clinical trial, funded by Cancer Research UK, investigating the delivery of this personalised IMRT treatment in patients with non-small cell lung cancer. We hope to demonstrate that the increase dose delivered to the tumor will lead to improved survival ” added Dr Faivre-Finn.

source : http://www.sciencedaily.com/releases/2014/08/140828091241.htm

Preclinical development of tumor therapeutic agent begins

amcure, one of the partners of which is KIT, now plans to use the funds acquired for the further development of candidate agents identified by the team of Dr. Veronique Orian-Rousseau, KIT, for the treatment of metastatic tumors. The candidate substances bind specifically to a certain so-called isoform of the surface molecule CD44 and, thus, specifically interfere with central signal paths of tumor growth, while other types of cells remain unaffected. New formation of blood vessels supplying the tumor (angiogenesis) and migration of cancer cells and their invasion into other organs (development of metastases) are inhibited. “Data from animal tests reveal that our molecules do not only stop the growth of primary tumors, but may also prevent metastasis development and cause the regression of existing metastases,” says Dr. Alexandra Matzke, Chief Scientific Officer of amcure. The clinical studies that are to start in the next years will show whether these positive effects will also occur in human patients without any side effects.

The target molecule of amcure’s development candidates, CD44v6, plays a significant role for many types of tumors. It was discovered in the 1990s by Professor Helmut Ponta and his team at KIT. CD44 and its isoforms are increasingly considered significant factors for the spreading and formation of metastases. Blocking the receptor CD44v6 might open up opportunities for a wide-ranging application in tumor therapy.

“If these observations will be confirmed by clinical trials with patients, amcure can lay the foundation for treating tumors much more effectively and with far fewer side effects,” emphasizes Dr. Harald Poth, Senior Investment Manager of LBBW Venture Capital.

The next development steps will be funded by a consortium headed by LBBW Venture Capital, with participations from KfW, MBG Mittelst√§ndische Beteiligungsgesellschaft Baden-W√ľrttemberg, S-Kap Beteiligungen Pforzheim, BioM AG as well as private investors. In addition, the company receives funding by the Federal Ministry of Education and Research (BMBF) under the special program Spinnovator managed by Ascenion GmbH. The funds are so-called series A funds provided by venture capital investors to support growth of the young KIT spinoff in the next years. Prior to and during the establishment of the company, amcure was financed by its partner KIT and the Helmholtz Association as well as from federal funds.

“The consortium around LBBW Venture consists of experienced investors having extensive networks. We are happy to have convinced them of our development approach so that now the next steps in the preclinical and clinical stages can be financed,” says Dr. Matthias Klaften, Chief Executive Officer of amcure.

source : http://www.sciencedaily.com/releases/2014/08/140827091948.htm