MCCIR AZ/GSK Update Seminar
|Starts:||15:30 11 Jul 2016|
|Ends:||16:30 11 Jul 2016|
|What is it:||Seminar|
|Organiser:||Faculty of Life Sciences|
|Who is it for:||University staff|
|Speaker:||Ben Mulhearn, Dr Amy Adlard|
Identifying immunological biomarkers to predict treatment response in rheumatoid arthritis
Rheumatoid arthritis (RA) is the most common autoimmune disease, affecting 5 – 10 in 1000 people. If left untreated RA can cause permanent joint damage and chronic disability. Good evidence shows that treating inflammation early leads to less irreversible damage and improves patient outcomes. Many patients will end up on a biologic drug having failed a 6-month trial of conventional drugs. Even so, not all patients will respond to their first biologic drug and there is currently no way to predict which drug will work first in each individual patient.
My aim is to develop an immunological assay that will help to predict which type of biologic drug will be effective in treating each individual patient with RA, prior to starting treatment. This will be achieved by stimulating peripheral blood mononuclear cells taken from patients who are about to start a biologic drug, immunophenotyping subjects, and using a multivariate statistical regression framework to correlate immune phenotypes with clinical response data collected at 3 and 6 months. An assay with this power would be a major leap forward for precision medicine in rheumatoid arthritis, and has the potential to apply to other autoimmune diseases treated with biologic drugs.
Exploiting the immune system in the treatment of cancer
Dr Amy Adlard
Invariant NKT cells are activated by cytokines or ligation of their invariant T cell receptor with glycolipid antigens, resulting in direct cytotoxicity and/or the production of Th1/Th2 cytokines. The ligand ?GalCer has shown limited efficacy as a cancer monotherapy in vivo, and required additional IL12 for optimal effect. We have tested a new Th1-skewing ?GalCer analogue, 7DW8-5, in both transgenic and implanted mouse models of melanoma. Fortnightly dosing with the ligand delayed tumour growth in both models, and resulted in activation of various immune cells in vivo.
I am also interested in the role of the lung microenvironment and promotion of tumour metastasis. Alveolar macrophages (AM) have major roles in resolution of lung inflammation and prevention of injury following viral infection, where they have been shown to increase expression of regulatory receptors long-term after resolution; however little is known regarding their role in metastatic disease. AM have recently been shown to be conducive of breast cancer metastasis in vivo, however, the mechanisms underlying this effect are largely unknown. I have begun to profile AM following s.c. implantation of tumour cells at a distant site, with the aim of revealing targets that could be manipulated to alter the innate activation threshold and reduce lung metastasis. Future studies will determine whether various tissue-specific immune landscapes following infection are more conducive or inhibitory to metastasis.
Travel and Contact Information
Michael Smith Lecture Theatre
Michael Smith Building