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Discovery
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Julia Schueler, DVM, Robert Mihalek, PhD

What's Hot in 2021: Oncology

The connection between gut health and immunotherapy is emerging; so are new trends in treating adult leukemia 

Modeling Interactions of the Immune System and the Microbiome

The role of the immune system has taken center stage in the development of new therapeutic agents to WHATSHOTLOGO200x269treat cancer patients.  Evidence has been accumulating in both animal models and clinical trials that response to immune modulating cancer treatments can depend on the types of bacteria present in the intestines of the host (i.e. the host’s intestinal microbiome). The absence of even a single species of bacteria can be the difference between a weak response and a strong response. Modeling these precise changes will require animal models that allow equally precise changes to the gut flora. Charles River Labs has been at the forefront in the development of germ-free mice that can serve as a “blank-canvas” to allow the repopulation of the gut with monocultures of individual species of bacteria and even defined mixtures of a variety of species. We are now investigating the role of the microbiome to evaluate how tumors grow in both germ-free mice as well as mice with defined gut flora. These studies will then allow an investigation of the efficacy of experimental immuno- and chemotherapeutic agents to determine the required conditions for an optimal tumor-killing response.  In short, elucidating this connection between the microbiome and immunotherapy efficacy will be a hot topic in months and years to come.
 

Robert Mihalek, PhD, Associate Director of Pharmacology, Charles River

 

New treatments beckoning for acute myeloid leukemia, plus a gold standard model to to test them

Acute myeloid leukemia (AML) is a molecular heterogeneous cancer with an overall poor prognosis, specifically in adults. For decades, treatment options were limited to cytotoxic therapy with or without subsequent allogeneic stem cell transplantation. With the advent of sequencing technologies and the new insights gained from those data, the treatment landscape for AML has evolved tremendously. Look for PDX models to lead the way in the study of new treatment options for AML. 

Using these sequencing technologies, actionable mutations such as FLT3 or IDH1/2 could be identified. Furthermore, antibody drug conjugates—a drug strategy that pairs an antibody with a small molecule chemo drug—have come into play together with several strategies utilizing immunotherapies  including immune checkpoint inhibitors, bispecific T cell engagers, chimeric antigen receptor (CAR)-T therapy) and the development of AML vaccines. To get these drugs off the ground and identify the most promising candidates in the pipeline a preclinical platform that covers the breadth and depth of the disease is critical. Patient derived xenografts (PDX), for years a gold standard in the preclinical drug development of therapies for solid cancers, is the best way forward in AML research. Representative panels of AML PDX are now available to the scientific community. Their clinical relevance has been demonstrated in numerous publications. Their predictive power will soon be determined as we begin to develop new treatment options for this devastating disease.

Julia Schueler, DVM, Research Director, Discovery Oncology, Charles River