8:00 am Coffee & Registration
9:00 am Chair’s Opening Remarks
Investigating Adenosine Signaling in the Context of the Hypoxic Tumor Microenvironment
9:10 am The Discovery of Biochemical & Immunological Mechanisms of the Hypoxia- A2-Adenosinergic Immunosuppression as the Foundation of the Conceptually Novel Immunotherapies of Cancer Using Several Classes of Anti-Hypoxia-A2- Adenosingergic Drugs
Synopsis
• Highlighting that extracellular adenosine-A2AR/A2BR adenosine receptors-cyclic AMP-PKA axis: provides the “OFF” signal to TCR activated T-Cells and inhibit NK cells and other immune cells, triggers the immunosuppressive transcription of all other known immunosuppressive molecules like PD1 via cAMP Response Element (CRE) and CREB transcription factor
• Discussing that i) inhibition of adenosine-generating enzymes like CD39/CD73 or ii) degrading the extracellular adenosine with adenosine deaminase (ADA) or iii) blockade of A2AR A2B adenosine receptors can promote antitumor immunity
• Understanding how the Hypoxia-HIF-1alpha axis triggers the upregulation of the extracellular adenosine-generating enzymes and is upstream of Adenosine-A2AR/A2BR extracellular receptors to inhibit the anti-tumor immunity
• Exploring that weakening of the Hypoxia in tumors by systemic oxygenation or by oxygenation agents and inhibition of HIF-1alpha by inhibitors will also weaken the immunosuppressive signaling by adenosine-A2AR/A2BR axis downstream and thereby can promote antitumor immunity
• Understanding that even the refractory to all current immunotherapies tumors is expected to be rejected if the blockade of immunological negative regulators (like PD1/CTLA) is combined with anti-Hypoxia-A2-Adenosinergic drugs
9:40 am Regulation of the Adenosinergic Pathway in the Tumor Microenvironment & In Response to Therapies
Synopsis
- Discussing the interaction between adenosine signalling in the tumor and with immune cells, particularly T cells and NK cells
- Exploring regulation of adenosine in response to different stages of disease, or therapeutic modalities
10:10 am Anti-hypoxia Treatments to Reprogram The Tumor Microenvironment & Improve Cancer Immunotherapies
Synopsis
• Addressing the acute need in strategies to target the most upstream stage of the hypoxia- A2-adenosinergic pathway of immunosuppression in the tumor microenvironment (TME)
• Emphasizing reprogramming the TME by eliminating tumor hypoxia to improve outcomes of current cancer immunotherapies
10:40 am Speed Networking
Synopsis
This session is the ideal opportunity to get face-to-face time with many of the brightest minds working in the Adenosine field and establish meaningful business relationships to pursue for the rest of the conference.
11:40 am Panel Discussion – Which Cancers Are Addicted to Adenosine?
Synopsis
• Which types of cancer are going to respond to adenosine-pathway targeted therapy?
• Does the tumor microenvironment and measuring adenosine differ for each type of cancer?
• Will targeting a certain point in the pathway be more effective for certain cancers?
Leveraging Biomarkers to Evaluate Disease, Identify Patient Responders & Monitor Treatment for Adenosine-Pathway Targeted Cancer Immunotherapy
12:10 pm Can Biomarkers Be Used to Identify Patients Who Are Most Likely to Benefit from Adenosine-Pathway Targeted Cancer Immunotherapy?
Synopsis
• Discussing the role of adenosine in the tumor microenvironment
• Divulging biomarkers as surrogates for the presence of adenosine
• Highlighting the A2AR as a biomarker for response to inupadenant in iTeos clinical trials
12:40 pm Lunch Break
Assessing the Optimum Target in the Adenosine-Pathway
1:40 pm Chair’s Remarks
1:45 pm Targeting CD39 in Malignancy: Immunotherapy & Inhibition of Angiogenesis
Synopsis
• Explaining the central role of CD39 in modulation of purinergic signalling viz. regulation of both extracellular nucleotide pro-inflammatory and nucleoside/adenosine immunosuppressive pathways
• Demonstrating CD39 as a major rate limiting enzyme for extracellular nucleotide scavenging as well as adenosine production; given regulated catalysis of ATP/ADP to AMP and impacts of e.g. ADP on feed-forward inhibition on CD73
• Exploring the major strengths and possible limitations of targeting CD39 in the immune system and vasculature
• Highlighting the development of the therapeutic possibilities involved in the targeting of CD39
• Discussing how and where CD39 has been successfully targeted, providing ground work for understanding pathobiology/preclinical models/early clinical studies
2:15 pm Combining CD39 & CD73 Inhibition for Treatment of Pancreatic Cancer
Synopsis
• Discussing non-redundant functions of CD39 and CD73 in PDAC
• Presenting data to reveal novel mechanisms-of-action
2:45 pm Afternoon Break
3:45 pm Dual Targeting of CD73 & A2AR for Effective Suppression of Adenosine Signaling
Synopsis
• Exploring how inhibitions of either adenosine generation or signaling by inhibiting CD73 or A2AR have been shown to be effective therapeutic approaches
• Analyzing why the co-blockade of CD73 and A2AR results in a more pronounced antitumor activity than blockade of either likely due to increased CD73 expression upon A2AR inhibition and compensatory activity of other adenosine receptors
• Developing small molecule inhibitors that dually target CD73 and A2AR for use in combination with approved immunotherapeutic agents
4:15 pm Using a Novel Reporter Mouse to Investigate A2AR Expression Within the Tumor Microenvironment
Synopsis
• Generating a reporter mouse that robustly exhibits GFP expression in A2AR positive cells
• Assessing how this reporter mouse allows interrogation of the cellular types and spatial location of cells expressing the A2AR within the tumor microenvironment
4:45 pm Interactive Roundtable Discussions
Synopsis
This session facilitates in-depth discussions among participants in an informal environment. After splitting into groups, participants will discuss key challenges and opportunities around their chosen topic:
- Combination of Therapy
- Investigating Drug Delivery Approaches for Appropriate Adenosine-PathwayTargeting