Participating Experts: James Allison, PhD, (MD Anderson), Gordon J. Freeman, PhD, (DanaFarber), and Philip J. Gotwals, PhD) (Novartis)
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Tumors manipulate their microenvironment in order to evade surveillance and elimination by the immune system. To do this, cancer cells can coopt inhibitory ligands and their receptors that regulate T cell effector function. Intervention targeting these pathways, known as immune checkpoint therapies, have been the subject of intense translational research and clinical development. This webinar explores how tumors exploit immune modulatory mechanisms to generate and thrive in their own immunosuppressive microenvironment, and how these mechanisms can be targeted to develop better therapeutic options. Topics covered include:

• A historical overview of immune checkpoint research and examination of the effect of mutational load on clinical response.
• How PD1 immunotherapy stops certain cancers from turning off the anticancer immune response.
• Discuss general therapeutic approaches to activating the immune system to treat cancer.

Table of Contents
0:00 Welcome and overview
2:46 James Allison speaker profile
3:35 Immune checkpoint blockade in cancer therapy: New inishgts, opportunities, and prospects for cures
4:18 FDA approval of antibodies targeting immune chckpoints
6:10 Dynamic integration of TCR and costimulatory signals
7:49 CTLA4 blockade enhances tumorspecific immune responses
9:04 AntiCTLA4 induces regression of transplantable colon carcinoma
10:29 AntiCTLA4/GVAX therapy activates the tumor vasculature and increases infiltration of tumors by CD4 and CD8 effector cells
12:10 The longest survivor on ipilimumab?
13:12 Ipilimumab in metastatic melanoma: pooled OS analysis including EAP data
14:16 AntiCTLA4, AntiPD1 comparison
15:13 Clinical activity: Ipilimumba and Nivolumab combination therapy
16:05 Mutational load varies in human cancers
17:12 Potential characteristics of immunogenic and nonimmunogenic tumors
17:21 Infiltrates in prostate cancer pre and post antiCTLA4 therapy
18:09 Improving survival with immunotherapy
18:55 Gordon Freeman speaker profile
19:34 Immunology has offered hope for 100 years
20:43 T cells need antigen recognition + costimulatory signals; PD1 pathway inhibits T cell activation
23:34 PD1 or PDL1 blockade allows reactivation of antitumor T cell responses
24:29 Phase I clinical trial of nivolumab – kidney cancer cohort
25:45 PD1 cancer immunotherapy tolerance, safety, adverse events
27:25 PD1 is better than chemotherapy for melanoma; overall response rates
28:39 The immune system recognizes protein coding changes in the tumor cell called neoantigens
30:04 Durable responses to immunotherapy compared to Braf tyrosine kinase inhibition
32:32 Understanding immunology and genetics has identified groups that respond well to PD1 and PDL1 therapy
33:40 Exhausted tumor infiltrating lymphocytes express multiple immunoinhibitory receptors
35:47 Future directions
38:08 Philip Gotwals speaker profile
38:53 Therapeutic targeting of the immune system to treat cancer
40:45 Targeted and immunemodulatory therapeutics are being combined in melanoma
43:55 A wealth of important targets for T cell modulation
44:37 LAG3 as a target for therapeutic approaches
46:06 Chimeric Antigen Receptor (CART) engineering
47:22 CTL019 therapy: overview of recent clinical data in hematologic malignancies
48:47 Targeting the immunosuppressive tumor microenvironment: IDO
50:50 Talimogene (TVEC) study
51:29 Local delivery may lead to systemic therapy: The abscopal effect
52:28 STING agonist for enhancing immune reponse to tumors
53:44 Towards complete, durable remission for cancer patients
54:32 Question and Answer

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