Which Oncology Models Are Right For Me?
Answer a few brief questions about your program to receive expert guidance on the most appropriate models for your program.
What type of cancer therapy are you pursuing?
What is the best way to demonstrate your agent’s mechanism of action?
How do I design my study if I only expect to see efficacy in combination with another agent?
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Cancer immunotherapies are designed to work in conjunction with a patient's immune system to increase native anti-tumor responses. In this field of study, conventional xenograft models lack relevance due to the animals’ immunocompromised status. A syngeneic mouse model (e.g., 4T1 and MC38 cell lines), however, provides an effective approach for studying how cancer therapies perform in the presence of a functional immune system.
If your agent reacts with mouse orthologues, syngeneic mouse models may be your best bet for your program. If you have a human-specific agent, then humanized models may be best for you.
Demonstrating that your therapeutic agent functions through the proposed mechanism of action in preclinical studies helps to support the clinical strategy for the development of your medicine. Moreover, these studies may identify clinical biomarkers of response that will simplify your clinical plan. The mechanism of action of immunotherapies can be evaluated in primary human cells (PBMCs) in vitro, or through flow cytometry of samples obtained from in vivo studies.
What is the best use of humanized mouse tumor models?
Humanized models represent the cutting edge of oncology in vivo pharmacology. They provide a proven platform for probing T cell-mediated efficacy for therapies like checkpoint inhibitor antibodies, and CAR-T cells. Some strains of mice offer the promise for probing other aspects of the tumor immunity cycle by supporting the growth of myeloid cell populations.
How do you plan to select the tumor models for your program?
Does your test article react with the mouse orthologue of your target?
All of these factors may be important considerations for model selection. Testing the response to your agent in vitro is a great way to determine the relative sensitivity of multiple lines to your targeted therapy. Bespoke or custom panels of cell lines can be selected based on a variety of criteria, including histotype, mutation profile, or gene expression profile. These profiles can be evaluated in the Charles River tumor compendium.
How do you plan to determine the dose and route of administration for your studies?
Determining the appropriate dosing route and regimen is critical for ensuring your study is designed appropriately to demonstrate the intended phenotypes. Preliminary formulation, PK, and tolerability studies will provide the information needed to achieve a desired level of exposure in appropriate tissues.
If an agent has no stand-alone activity for inhibition of tumor growth, combination studies can be facilitated by establishing assays that measure target engagement (PD assays). This will allow determination of an effective dose that can be combined with the standard agent. In some cases, these effects can be reproduced in vitro and higher throughput combinations can be evaluated prior to design of an in vivo study. If the combination must be conducted in vivo, Charles River has an extensive database for standard agent response to help select the dose and regimen needed to provide a window to see a combination effect.
Do you know which types of oncology models are you interested in?
Do you know which types of oncology models are you interested in?
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Interested in learning more about the pros, cons, and applications of the major mouse models currently used in cancer research and how to use them synergistically to meet your goals?
The Planning Strategy: Syngeneic, PDX, Humanized, Xenografts, Orthotopics, and More.
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