March 20, 2013.docx

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Cell and Systems Biology
Gray- Owen

MIJ March 20, 2013 Therapeutic Vaccines Vaccines targeted for infection – for protection against infection – prophylactic so given before the infection Prophylactic vaccine – aim to prevent infection or disease – Cancer immunity – - In this individual, immune system not controlling infection - So these tumours avoid immune response - Immune system capable of using different means to attack cells – so it doesn’t seem to agree with supposition that immune system could not control tumour in cancer patient - In contrast to pathogen, tumour looks like self – so to immunize against it, by nature it is an AUTOIMMUNE RESPONSE – successful vaccine activates, reactivates immune system – to allow to detect transformed cells – - Problem – pathogen – Nmeng capsule looks like sugar that expressed during neonatal development – case of where antigen resembling self – so no immune response - In most cases, unless cancer driven by pathogenic infection, have to develop immune response How do you target a self cell? – ACTIVE AREA OF RESEARCH Three different strategies in how to use immune system to target tumours – vaccines against pathogen s- get antigen against tumour – soething that would be over-expressed in that tumour relative to most cells in body – very difficult – some things ex. CEACAM receptor 5 – this is upregulated on tumours in colon – upregulated when there is a tumour – during tumour, normal differentiation breaks down – have mass of cells that is tumour so CEA exposed to bloodstream – immune response from blood side – attack whole intestinal lining – depending on antigen and target – different strategies – binding protein and formulating it in various ways to elicit immune response – Spuleucel – provenge – immune based drug against Not a single formulation – personalized medicine example Isolate peripheral blood cells – invitro, load with GMCSF, a cytokine that activates cells and cause inflammation – prostate specific inflammation – antigen isonly in prostate gland, normally expressed there, but more of it in the tumour – Activate T cells and cause immunity Placebo – probability of survival over time If have the treatment early on – had life expentancy increased Four to five years – Castration-resistant – severe examples of prostate cancer – cannot be treated or surgically removed Vaccination with tumour-specific tumour derived antigen in first remission improves disease-free survival in follicular lymphoba B cell lymphoma – expanded drastically in individual – novel epitopes on those B cells – this epitope is the antibody – so have something to target Immunize with antibody; monitor survival B is results – actually was HPV tumours – immunize against HPV drug antigen in cells or remains on cells and cause improved survival and reduced – increase time until disease – similar thing – whereas this paper is targeting B cells Adaptive T cell transfer – second general strategy A lot of different antigens – example of first-pass approach – first kind of treatment – deciding on what antigen should be targeted and what other treatments it should be combined with – promising data One of the early approaches taken was to inject bacterial lysates into tumour – Direct injection into tumour and make effectrs – hope this elicits immune response to overcome immunoscuppresion there and increase promotion of tumour cell uptake so epitopes expressed on APC in tissues – new addition to this is to actually damage the tumour, using laser – so internal antigens and epitopes released T cells in tumours – belief that they already have tumour specificity, that’s why they’re there – some of these are actually not protective but maybe suppressive type T cells – wrong type of T cell to expand if want to target tumour Surgically remove portion of tumour – expand in vitro - cross link T cell receptor – get rapid expansion of these cell sin vitro – if there is leukocytes – lymphocytes recruited to tumour, they must be there for a reason – and
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