Ebook Fast facts - Non-small-cell lung cancer: Part 2
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Ebook Fast facts - Non-small-cell lung cancer: Part 2
Ebook Fast facts - Non-small-cell lung cancer: Part 2
5 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department, Ebook Fast facts - Non-small-cell lung cancer: Part 2 Gustave Roussy, Villejuif, FranceIn general, non-small-cell lung cancer (NSCLC) is associated with tumor DNA damage and mutations induced by carcinogens in tobacco smoke. In the mid-1990s an antibody to one of rhe murine immune checkpoints was found to cure tumors in vivo.1 The first antibody to cy Ebook Fast facts - Non-small-cell lung cancer: Part 2totoxic T-lymphocyte-associated protein 4 (CTLA-4) was licensed 15 years later for rhe treatment of melanoma. This reignited the pursuit of immunotherEbook Fast facts - Non-small-cell lung cancer: Part 2
apies in the management of cancer, including NSCLC.2 Known as immune checkpoint inhibitors, these therapies target the programmed cell death 1 (PO-l) 5 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department, Ebook Fast facts - Non-small-cell lung cancer: Part 2sed on activated T cells, B cells, natural killer cells, monocytes and dendritic cells. The effector function of T cells that express PD-1 in the tumor microenvironment can be suppressed when PD-1 is coupled to the ligand PD-L1 (B7-H1) or PD-L2 (B7-DC) on tumor cells, thus preventing an immune attac Ebook Fast facts - Non-small-cell lung cancer: Part 2k on the cancer.3 The PĐ-L1 and PD-L2 ligands cross-compere for PD-1 binding; although PD-L2 has a sixfold higher binding affinity for PD-1, it has loEbook Fast facts - Non-small-cell lung cancer: Part 2
wer levels of expression, so that PD-L1 is the best ligand to target. Inhibition of the PD-1/PD-L1 immune checkpoint using monoclonal antibodies (mAbs5 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department, Ebook Fast facts - Non-small-cell lung cancer: Part 2opmentSeveral drugs are in development (Table 5.1). The PD-1 inhibitors are immunoglobulin (Ig)G4 isotypes, while the PD-L1 inhibitors are IgGl isotypes and are able to bind Clq and activate the complement41©2016 Health Press Ltd. www.fastfacts.comFast Farts:Non-Small-Cell Lung CancerFigure 5.1 Tumo Ebook Fast facts - Non-small-cell lung cancer: Part 2r cells can present antigen to activated T cells, upon T cell activation, programmed cell death 1 (PD-1) receptors are expressed on T cells. When coupEbook Fast facts - Non-small-cell lung cancer: Part 2
led to the programmed cell death ligand 1 (PD-L1) receptor on the tumor cell, the normal immune response is inhibited, preventing an attack on the tum5 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department, Ebook Fast facts - Non-small-cell lung cancer: Part 2or immunity.pathway. The Fc region of naturally occurring IgGl is able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), while the Fc portion of IgG4, in general, does nor. However, this function is generally engineered out of Fc regions, bec Ebook Fast facts - Non-small-cell lung cancer: Part 2ause ADCC, when binding to the PD-1/PD-L1 axis, could potentially cause increased toxicity through killing immune cells expressing PD-1/PD-L1 and be pEbook Fast facts - Non-small-cell lung cancer: Part 2
otentially less effective. Avelumab is one of rhe antibodies that has retained rhe ADCC function.PD-L1 expression (see Table 5.1) has been an early bi5 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department, Ebook Fast facts - Non-small-cell lung cancer: Part 2test predictive value, which is seen in about 30% of NSCLC rumors (see page 47).©2016 Health Press Ltd. www.fastfacts.com© 2016 Health Press Ltd. www.fastfacts.comTABLE 5.1Immune checkpoint inhibitors in clinical developmentDrugOther names during developmentTrade nameClass of agentPD-L1 companion di Ebook Fast facts - Non-small-cell lung cancer: Part 2agnostic testPD-1 inhibitorsPembrolizumabMK-3475, lambrolizumabKeytrudaHumanized, lgG4 isotype mAb against PD-1Test: PD-L1 IHC 22C3 Dako Membranous stEbook Fast facts - Non-small-cell lung cancer: Part 2
aining of PD-L1 on tumor cells using IHCNivolumabONO-4538, BMS-936558, MDX1106OpdivoFully humanized, lgG4 isotype mAb against PD-1Test: PD-L1 IHC 28-85 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department, Ebook Fast facts - Non-small-cell lung cancer: Part 2t: SP142 clone - Roche in house PD-L1 expression on tumor cells and/or infiltrating lymphocytes using IHC CONTINUED•uLU■pg o2E o oOJÒ(/)TABLE 5.1 (CONTINUED) Ebook Fast facts - Non-small-cell lung cancer: Part 25 Immuno-oncologyRajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK: and Jordi Remon MD, Medical Oncology Department,Gọi ngay
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