Download Free Medical Immunotherapy PowerPoint Presentation

Immunotherapy PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

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 : 1922 | Downloads : 5

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

IMMUNOTHERAPY Vanesa Gregorc MD IRCCS San Raffaele, Milano
Slide 2-

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
Slide 3-

NOVEL ASPECTS Immune-related response criteria Endpoints The immune-related toxicities All differ considerably from conventional cytotoxic agents and targeted therapies
Slide 4-

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.
Slide 5-

ANTI PD1-PDL1 ANTI CTLA4 MAGE A3 MUC1 BELAGEN-PUMATUCEL L IMMUNOMODULATORS VACCINES NSCLC IMMUNOTHERAPY Tumor/T cells
Slide 6-

Mechanism of action IMMUNOMODULATORS
Slide 7-

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.
Slide 8-

OF T CELL
Slide 9-

OF TUMOR CELL
Slide 10-

Clinical Development of inhibitors of PD-1 immune Checkpoint
Slide 11-

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
Slide 12-

1YEAR SURVIVAL=42%, 2 YEAR SURVIVAL 24%
Slide 13-

Lambrolizumab in NSCLC Garon E. et al Abstract MO18.02 IALS 2013
Slide 14-

INHIBITORS OF PDL1- phase I trial
Slide 15-

Inhibitors of PD-L1-Activity in NSCLC
Slide 16-

PD L1 Expression Pd-L1 Is broadly expressed in NSCLC
Slide 17-

ppt slide no 17 content not found
Slide 18-

ppt slide no 18 content not found
Slide 19-

UPDATE
Slide 20-

UPDATE
Slide 21-

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.
Slide 22-

ppt slide no 22 content not found
Slide 23-

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
Slide 24-

[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
Slide 25-

RESULTS
Slide 26-

[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
Slide 27-

OUTCOME BY HISTOLOGY OS IN SQUAMOUS
Slide 28-

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
Slide 29-

LUNG CANCER VACCINATION. NSCLC ONGOING PH 3 TRIALS > 8000 Reported ASCO 2013 Reported ESMO2013
Slide 30-

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.
Slide 31-

[TITLE] START TRIAL – STUDY DESIGN stage IIIA/B post CT/RT (DC)
Slide 32-

START TRIAL – PRIMARY ENDPOINT OS
Slide 33-

START TRIAL – SECONDARY ENDPOUINT TIME TO PROGRESSION
Slide 34-

START TRIAL – OS SUBGROUP ANALYSES BY RANDOMIZATION DATA
Slide 35-

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.
Slide 36-

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
Slide 37-

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