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VCS 2020: New Strategies to Stimulate Effective Tumor Immunity by Modifying the Tumor Microenvironment

VCS 2020: New Strategies to Stimulate Effective Tumor Immunity by Modifying the Tumor Microenvironment

VCS 2020: New Strategies to Stimulate Effective Tumor Immunity by Modifying the Tumor Microenvironment

Stephen Dow
Stephen Dow
on behalf of Missouri Veterinary Medical Association

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Launch date: 22 Nov 2020
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Last updated: 13 Feb 2021

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Description

"New Strategies to Stimulate Effective Tumor Immunity by Modifying the Tumor Microenvironment
Cancer immunotherapy: Current Challenges: The promise of cancer immunotherapy has now been rapidly realized, in studies largely conducted just over the past decade. Despite tremendous advances, challenges remain, particularly with respect to treatment of immunologically “cold” tumors such as pediatric sarcomas and malignant gliomas. Solid tumors in general represent a significant barrier to adoptive T cell transfer, and checkpoint antibody therapeutics are generally relatively ineffective in low T cell infiltrated cancers. Personalized cancer vaccines are difficult currently to produce quickly, and induction of effective immunity is not always possible.
Role of the TME in regulating tumor immunity. The immune suppressive tumor microenvironment (TME) is a major impediment to effective cancer immunotherapy. Particular TME barriers include immune suppressive stromal cells (eg, tumor macrophages, cancer fibroblasts, Tregs) and physical stromal barriers such as fibrotic responses and extracellular matrix. Overcoming these local tumor barriers represents a fundamental challenge to successful cancer immunotherapy.
Modifying the TME. One approach to reduce immune suppression within the TME is to deplete or functionally alter immune suppressive cell populations. We have evaluated several different strategies. In one approach, macrophages can be depleted directly (eg, liposomal clodronate) or activated locally (eg, by injection of TLR3 or 9 agonists). A third strategy, which we have been investigating in both osteosarcoma and glioma trials, is to induce sustained blockade of recruitment of inflammatory monocytes to the tumor, which over time leads to macrophage depletion. To accomplish this clinically in dogs, we have repurposed the angiotensin receptor blocker (losartan) as a novel CCR2 antagonist and monocyte migration inhibitor, together with toceranib, which leads to Treg depletion. The two drugs in combination have been shown to induce tumor regression in metastatic osteosarcoma and to enhance vaccine effectiveness in glioma. Additional studies are underway to more fully define the mechanisms of action of these drugs in canine cancer."

Exam offered and MVMA CE certificate issued following presentation.

Objectives

Understand why two categories of drugs (ARBs and beta blockers) have immune modulatory properties and how these properties can be used to target the TME to relieve immune suppression.
Understand why toceranib (Palladia) has immune modulatory properties that make it a drug that can also be used to modify the TME.
Understand why it makes sense to combine multiple different categories of immune modulatory drugs in cancer immunotherapy trials.
Stephen Dow

Author Information Play Video Bio

Stephen Dow
on behalf of Missouri Veterinary Medical Association

Steven Dow, DVM, PhD, DACVIM; Colorado State University
Dr. Steven Dow is a Professor of Immunology in the Department of Clinical Sciences as well as the Director of the Center for Immune and Regenerative Medicine at Colorado State University. His lab investigates immune responses in infectious diseases, cancer, and allergic and autoimmune diseases and is currently studying the immune modulatory effects of mesenchymal stem cells (MSC) and the use of MSC to treat chronic kidney disease, chronic liver disease, and chronic wound infections in dogs and cats.
Dr. Stanley’s first faculty appointment was at the University of Edinburgh in Scotland but she has been at Michigan State University since 1999. Stanley’s clinical interests are in all aspects of soft tissue surgery, particularly upper respiratory, wound management and cutaneous reconstructive techniques. Stanley runs two research labs – in upper respiratory diseases and wound healing – for which she runs numerous studies and clinical trials. Her current upper respiratory studies are laryngeal paralysis polyneuropathy in Labradors and Newfoundlands, Norwich terrier upper airway syndrome and the brachycephalic upper airway. Her current wound healing studies are in incisional negative pressure wound therapy, amniotic membranes and honey-based products. She publishes frequently, has received many teaching awards and lectures widely at a national and international level.

Current Accreditations

This course has been certified by or provided by the following Certified Organization/s:

  • Missouri Veterinary Medical Association
  • 0.75 Hours -
    Exam Attempts: 3
    -
    Exam Pass Rate: 60

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