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Immunotherapy PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "IMMUNOTHERAPY" by Vanesa Gregorc MD.

This medical PowerPoint presentation talks about immunotherapy. Immunotherapy is a type of medical treatment that involves using the bodys immune system to fight diseases such as cancer, infections, and autoimmune disorders. This approach works by boosting or modifying the bodys natural defense mechanisms to help it identify and attack harmful cells.

Tags : Immunotherapy, immune system

Published on : Mar 16, 2023 | Views : 928 | Downloads : 2

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IMMUNOTHERAPY Vanesa Gregorc MD IRCCS San Raffaele, Milano
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LUNG CANCER AS AN IMMUNOLOGIC-MEDIATED DISEASE AND TARGET FOR IMMUNOTHERAPY Although many immunotherapies are being investigated in NSCLC, currently none have been FDA approved, as vaccines and other immune-modulators have yet to demonstrate considerable improvements inOS in phase III clinical trials
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NOVEL ASPECTS Immune-related response criteria Endpoints The immune-related toxicities All differ considerably from conventional cytotoxic agents and targeted therapies
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RESPONSE EVALUATION FOR IMMUNOTHERAPY Permissive not restrictive RECIST/mWHO modified by immunological criteria First radiological examination the most critical (pseudo-progressions) irResponders with new lesions also but decrease in baseline lesions PD should be confirmed after 4 w Wolchok JD, et al Clin Cancer Res 2009; 15:7412-7420.
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ANTI PD1-PDL1 ANTI CTLA4 MAGE A3 MUC1 BELAGEN-PUMATUCEL L IMMUNOMODULATORS VACCINES NSCLC IMMUNOTHERAPY Tumor/T cells
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Mechanism of action IMMUNOMODULATORS
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PROGRAMMED DEATH-1 IMMUNE CHECKPONT (PD-1) PD-1 (cell receptor) is overexpressed on NSCLC-infiltrating T cells and these are functionally exhausted cells Ligands: PDL-1 and PDL-2 (tumor cell /APC) Higher tumoral PDL-1 expression correlates with decreased OS RATIONALE Blocking the PD-1 or PDL-1 pathway would restore/promote the function of chronically exhausted tumor-specific T cells and decrease tumor-induced immune suppression Zhang Y et al. Cell Mol Immunol. 2010;7:389- 395.
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OF T CELL
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OF TUMOR CELL
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Clinical Development of inhibitors of PD-1 immune Checkpoint
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Inhibitors of PD-1 – Phase I trial CT-O11 (0.2-6.0mg/kg N=17 CT-O11 0.2-6.0 mg/kg IV
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1YEAR SURVIVAL=42%, 2 YEAR SURVIVAL 24%
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Lambrolizumab in NSCLC Garon E. et al Abstract MO18.02 IALS 2013
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INHIBITORS OF PDL1- phase I trial
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Inhibitors of PD-L1-Activity in NSCLC
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PD L1 Expression Pd-L1 Is broadly expressed in NSCLC
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UPDATE
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UPDATE
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EGFR STATUS AND IMMUNOTHERAPY EGFR wild type has higher PD-L1 expression vs EGFRm MO18.01 EGFR status and MPDL3280A Activity in NSCLC Horn et al.
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IPILIMUMAB T cell TCR CTLA4 APC MHC CD28 B7 CTLA-4 blocks co-stimulation: No T-cell activation Adapted from Lebbé et al. ESMO 2008 T cell TCR CD28 CTLA4 APC MHC B7 Ipilimumab blocks CTLA-4: T-cell activation ipilimumab T cell TCR APC MHC CD28 B7 Co-stimulation via CD28: T-cell activation APC, antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte antigen-4; MHC, major histocompatibility complex; TCR, T-cell receptor. Adapted from DoomC. 2012 PILC
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[TITLE] Adapted by J. Brahmer, 2013 ASCO Annual Meeting Lynch TJ, et al. phase II study. J Clin Oncol. 2012;30:2046-2054. RANDOMIZED PHASE II STUDY OF IPILIMUMAB AND CT IN ADVANCED NSCLC
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RESULTS
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[TITLE] Adapted by J. Brahmer, 2013 ASCO Annual Meeting Lynch TJ, et al. phase II study. J Clin Oncol. 2012;30:2046-2054. RANDOMIZED PHASE II STUDY OF IPILIMUMAB AND CT IN ADVANCED NSCLC
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OUTCOME BY HISTOLOGY OS IN SQUAMOUS
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Adapted by J. Brahmer, 2013 ASCO Annual Meeting ONGOING PHASE III OF IPILIMUMAB IN SQUAMOUS CELL LUNG CANCER Double blind Primary endpoint: OS Secondary: OS in patients who receive one dose of ipi/placebo, PFS, RR R Carbo –paclitaxel - placebo Carbo –paclitaxel - ipilimumab Carbo AUC 6 Paclitaxel 175 mg/mq Ipilimumab 10 mg/kg q3w
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LUNG CANCER VACCINATION. NSCLC ONGOING PH 3 TRIALS > 8000 Reported ASCO 2013 Reported ESMO2013
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Butts ASCO2013 L-BLP25 MUC1 is a mucinous glycoprotein that is overexpressed and aberrantly glycosylated in many human malignancies. BLP25 is a synthetic, liposomal cancer vaccine that targets the extracellular tandem repeat sequences of the MUC1 tumour-associated antigen.
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[TITLE] START TRIAL – STUDY DESIGN stage IIIA/B post CT/RT (DC)
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START TRIAL – PRIMARY ENDPOINT OS
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START TRIAL – SECONDARY ENDPOUINT TIME TO PROGRESSION
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START TRIAL – OS SUBGROUP ANALYSES BY RANDOMIZATION DATA
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STOP TRIAL stage III/IV in DC after 1° line belagenpumatucel-L Giaccone et al.ESMO 2013 Primary endpoint: OS Other endpoints: PFS, RR, QoL, CNS metastases, safety Belagenpumatucel-L(Lucanix®) uses genetically modified whole tumour cells to stimulate the patient's own immune system to attack the tumour. It is comprised of 4 transforming growth factor (TGF)-ß2 antisense gene-modified, irradiated, allogeneic NSCLC cell lines.
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STOP TRIAL did not meet predefined end point-OS BUT: Significantly prolonged overall survival in patients who began belagenpumatucel-L within 12 weeks of the completion of front-line chemotherapy or RT in Sq and Non-Sq
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conclusions Immunotherapy has promising anti-tumor activity in NSCLC and an unique set of side effects consistent with the immune mechanism of action Patient selection (biomarker) might be the key to further development as a single agent and in combination with other therapies Phase III trials are ongoing in order to make immunotherapy a reality for the treatment of NSCLC