JUN 02, 2021 1:30 PM PDT

Keynote Presentation: Hypoxia Drives Tumor Immune Suppression and Immunotherapy Resistance

C.E. Credits: P.A.C.E. CE Florida CE
Speaker

Abstract

Hypoxia is pervasive across human cancer and its association with poor outcomes and aggressive malignant phenotypes has been increasingly appreciated.  Previously, we and others described how T cells are virtually absent from hypoxic zones of tumors. Serendipitously, we discovered that the hypoxia-activated prodrug (HAP) TH-302 could potently reduce hypoxia in murine models of prostate, pancreatic and head and neck cancer. With this tool, we were able to test the hypothesis that reversal of hypoxia might restore T cell infiltration and improve sensitivity to T cell checkpoint blockade in “cold” tumors.  Across both transplantable and spontaneous murine models of prostate cancer, we have shown that the combination of TH-302 and antibody blockade of CTLA-4 and PD-1 synergize in curing, regressing, or controlling these tumors.  With our collaborator Dr. Hong, we launched a clinical trial of the combination of TH-302 (evofosfamide) and ipilimumab (αCTLA-4) in 2017 (NCT03098160) which has revealed the potential of this combination to regress established metastatic prostate and head and neck cancers in patients, and to significantly extend progression-free survival in late stage pancreatic cancer.  While TH-302 can restore tumor oxygen supply, we have observed across multiple human and murine cancers that elevated oxygen metabolism (OxPhos) at the tumor cell level metabolically cripples T cells resulting in resistance to immunotherapy.  Ongoing efforts in the lab are exploring mechanisms to selectively disable tumor oxygen hyper-metabolism, as well as alternative approaches to further dampen hypoxia in cancer.

Learning Objectives:

1. Describe the impact of hypoxia on tumor immunity

2. Identify approaches for reducing tumor hypoxia

3. Describe the clinical impact of hypoxia reduction on sensitivity to CTLA-4 blockade


Show Resources
You May Also Like
FEB 24, 2021 10:00 AM PST
C.E. CREDITS
FEB 24, 2021 10:00 AM PST
DATE: February 24, 2021 TIME: 10am PST Automated lab instruments such as liquid handlers and cell sorters are increasingly common in all types of laboratories, driving fast results for labor...
JAN 21, 2021 8:00 AM PST
JAN 21, 2021 8:00 AM PST
Date: January 21, 2021 Time: 8:00am (PST), 11:00am (EST) Today, critical reagent characterization is a key component in the overall workflow to establish robust ligand binding assays (e.g.,...
MAR 30, 2021 8:00 AM PDT
MAR 30, 2021 8:00 AM PDT
DATE: March 30, 2021 TIME: 08:00am PST In this talk, we will discuss the value of moving towards modular and automated, closed-system technologies designed to enable scalable and cost-effect...
APR 21, 2021 10:00 AM PDT
C.E. CREDITS
APR 21, 2021 10:00 AM PDT
Date: April 21, 2021 Time: 10:00am (PDT), 1:00pm (EDT) Serological testing for SARS-CoV-2 has been steadily adopted into clinical practice over the course of this pandemic. In this webinar,...
APR 07, 2021 9:00 AM PDT
C.E. CREDITS
APR 07, 2021 9:00 AM PDT
One challenge pharmaceutical companies face, is moving promising biotherapeutic products into the clinic as fast as safely possible. Devoting the correct amount of time and resources to earl...
JUN 24, 2021 8:00 AM PDT
Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
C.E. CREDITS
JUN 24, 2021 8:00 AM PDT
Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
Date: June 24, 2021 Time: 8:00am (PDT), 11:00am (EDT) Cardiovascular disease is a leading health problem, affecting almost 30% of individuals in the developed world, and comprises a wide ran...
Loading Comments...
Show Resources