Download How to select the right oncology model

Informational e-book:
How to select the
right oncology model
Optimizing your oncology research
When it comes to successful oncology research, one area that can help increase your success rate is choosing the right animal model right from the
start. Your compound’s effect on tumors is influenced by the right animal model. What’s more, if the right model is chosen from the beginning, you
can accelerate your research and avoid any testing redundancy or unnecessary repeat steps.
No matter what your oncology research focus, your success starts with the right animal model.
There are thousands of cell lines and many animal models to choose from. Previous studies to yours may have already shown the success or failure
in testing certain compounds or therapies with select animal models. Your ability to research and leverage this earlier work can have a dramatic
effect on the time, resources and dollars you put into your research.
There are various factors at play when it comes to selecting the best model for your research. First, many types of animal models exist, such as
haired versus hairless, immunodeficient versus immunocompetent, spontaneous versus inducible, and so on. Next, you have the various requirements
for the testing of your compound, including the characteristics of your cell line, the duration of your study, model characterization and availability
and affordability of the animal models. Once you have chosen your model, there are other important factors to consider, including the model’s diet
and bedding, its housing and husbandry, etc.
In this e-book, we provide a comprehensive base of information to help you select the right model and environment for your oncology research.
All insights and points made herein, are intended to be extrapolated across the various oncology research segments. In other words, please stay
with us and proceed through the rest of this e-book regardless of what your research goals are.
This e-book will discuss the following aspects of oncology research:
+ Importance of selecting the right oncology research rodent model
+ Factors to consider when selecting your animal model
+ Types of oncology rodent models
+ Model selection process
+ Other factors to consider
+ Key terminology
1
Importance of selecting the right oncology model
Your time, financial and personnel resources
are precious and must be allocated to oncology
programs primed with the highest possible
success potential.
Your oncology animal model lies at the very
heart of your entire oncology research program.
The specific model you choose, along with any
preconditioned factors, can most certainly mean
the difference between success and failure.
Your research model serves as the basis for your
testing, and the model you choose must grow
the specific cell line you are using, or your results
won’t support a successful outcome.
The wrong animal model for your cell line of
interest may not produce the desired tumor.
Therefore, you need a model that has all the
characteristics necessary to produce the right
tumor and in the right amount of time. The
model can then effectively serve as an accurate
precursor to testing in larger animals and humans.
If you select the wrong model, you may have
to go back and retest in another model in order
to create the necessary tumor and/or reaction.
Ineffective model selection can lead to:
+ Longer time to market
+ Additional expenditure on models than
originally necessary
+ More resource expenditure than
originally necessary
+D
elaying subsequent compounds that are
in the cue for development
+ Patient health concerns (especially with
personalized medicine)
Let an experienced research services company
help you decide on the right model for your
research, and be sure to consult all relevant
previous research to uncover what has already
worked for your cell line.
Don’t fall victim to this scenario:
“I purchased this animal model and my cell
line didn’t grow, or my tumors grew but
they regressed.”
If you’re at this stage, you may already be several
months into your research, and this dramatically
slows down your research efforts.
While there may be some level of troubleshooting
that can occur to remedy this issue, it may
simply be the wrong animal model for your
research. After all, if you can’t get your implanted
cell line to grow and produce a tumor within
your animal model, then you can’t test your
compound. The animal model has to be able
to produce a tumor of the adequate size and
composition or your model is ineffective for
your research program.
2
Factors to consider
In order to select the most appropriate immunodeficient model for your
research, you need to consider a host of factors, spanning the rodent model’s
aging characteristics, its genetic makeup, the behavior of its immune system,
the desired length of your study and so on. These and other considerations
can significantly impact the success of your oncology research.
Specific factors:
Genetics: What are the specific gene features of the mutation within your
model, including where it is expressed and how it functions? How does
the mutation impact immune response? Different models can lead to very
different results.
CATEGORIES
OF TISSUES:
- Human
- Murine
- Cancer stem cells (CSC)
- Patient-derived (PDX)
Envigo offers a CELL LINE
REFERENCE TOOL,
featuring research on over
350 different cell lines.
Gender: Is the type of cancer you are studying gender specific, for example,
breast or testicular cancer? Other cancers, such as brain cancer, for instance,
may be effectively studied in either gender.
Aging: What is the model’s immune status as it ages and also the typical
lifespan of the model? If it has a shorter life span or the tumor regresses
due to age-related immune function before your research concludes, your
oncology study will be impacted.
Immune system: What are the research model’s immune characteristics?
How immune deficient does your model need to be? It is also important to
understand other immune-based characteristics such as its sensitivity level
to radiation, for instance.
Study duration: The desired length of your study will impact your model
selection as some models live longer than others, some may become leaky
after a period of time, while others will allow for growth of other, irrelevant
types of tumors.
3
Availability: Are you able to acquire the right quantity in the right location
to complete your research?
Animal vivarium: What types of housing facilities will be important – do
you have appropriate caging for immunodeficient models?
Published references: What previous research has been conducted for
your cell line and research scope? Researching previous cell line results with
your animal model can keep you from reinventing the wheel.
Diet: Laboratory animal diets can impact your study results. Do you know
what type of diet your model is maintained on? Nutrient and non-nutrient
components can impact your results, such as:
+C
hlorophyll (if performing imaging studies, e.g.) – chlorophyll in
alfalfa meal fluoresces at a wavelength that interferes with optical
imaging of tumors (tumor tissue is often in the same color spectrum)
+P
hytoestrogens – influences tumor growth in unpredictable ways
+N
itrosamines – does your diet contain animal by-products that
can become carcinogenic?
+ Adjusted fat and protein levels – can provide a diet that is different
than a maintenance requirement
Bedding and enrichment: Is the appropriate bedding being used for your
animal model (for example, nude mice require a less dusty environment)?
Are you working with a hairless or nude model that requires a softer bedding?
Are you offering the appropriate enrichment for your animal model?
As you can see, there are literally countless factors to consider when choosing
the very best model for your research program.
4
Types of oncology models
There are a number of different types of rodent models to help you with your oncology research, varied by immune status, presence or absence of
hair coat, degree of heterogeneity, and susceptibility to growing desired tumor types.
Immunodeficient models:
+ Athymic nude mice
+ SCID mice
+ Beige nude XID mice
+ Beige SCID mice
+ SHrN® mice
+ Athymic nude rat
Immunocompetent models:
+ Traditional models: examples include BALB/c mice, Sprague Dawley® and Fisher 344 rats
+ Spontaneous and inducible models: examples include A/J, B6D2F1, C3H, CBA, and C57BL/6 mice; ACI, Brown Norway, and Wistar Furth rats
Preconditioned models:
+ Surgical modification - preconditioned specifically to your study needs. This includes the model already having one of the following procedures:
- Soft tissue: Procedures to support your research protocol can include castration, vasectomy, or ovariectomy.
- Catheterization: Catheters can be surgically inserted to support sampling blood and/or infusing compounds.
+ Diet maintenance – Is your model inducible, and does it require a specific diet (for example, tamoxifen)? Does your study evaluate the
effects of gene overexpression / downregulation and require a Doxycycline (Dox) diet?
5
Model selection process
As stated earlier, your research model selection lies at the crux of your
oncology research program. Selecting the right model can mean the difference
between months or even years of unnecessary and costly testing. You want
to do everything you can to narrow in on the very best animal model for your
program, from the very beginning. To accomplish this, you can certainly
consult an experienced research services company with a specialty in oncology
modeling. If you chose to make the right rodent model selection on your
own, there are various recommended steps you ought to follow, including:
1. D
rug type - determine the type of oncology drug you are going to
develop. For example, is it a checkpoint inhibitor, meaning an immunocompetent model may be acceptable?
2. Previous research - consult previous cell line research on oncology modeling
to help you understand what has and has not worked in other labs.
3. T
umor growth rate – determine when you are targeting a slow or fast
growing tumor; is it easy or difficult to grow?
4. Leakiness of the model – consider the model background and potential
impact of leakiness on your study.
5. Immune system – decide what degree of immunodeficiency your
research requires.
6. S
tudy length – determine the duration of your study (for example, many
immunodeficient models perform better when implanted at a younger age).
7. C
ell line injection - identify how you need to implant your model with
your cell line of interest – subcutaneous or orthotopic?
8. C
ompound quantity - determine how much of your compound is available
to be tested to determine if a rat or mouse model may be more appropriate.
9. M
odel availability - understand how available the specific model you
require is, and will you be able to source the quantity you require?
10. Select and procure your model.
SPECIFIC
ONCOLOGY
FIELD
UNDERSTAND
MODEL
CLASSIFICATIONS
MODEL
AVAILABILITY
MODEL
SELECTION
PROCESS
STUDY
REQUIREMENTS
STUDY
PURPOSE
CELL LINE
RESEARCH
6
Terminology
Immunology
+ Cell-mediated immunity – plays a major role in transplant rejection and removal of virus-infected cells, and defends against cancers
+ Humoral immunity – mediated by secreted antibodies produced in B cells, functions in the serum, and eliminates pathogens and toxins
+ T cell – binds with antigens to recognize targets (e.g. tumor antigens on the surface of cancer cells)
+B
cell – is produced in bone marrow, is a white blood cell that produce antibodies, and it performs the role of antigen-presenting cells
(APCs). Memory B cells live for a long time. Naïve B cells have not been exposed to an antigen.
+N
K (natural killer) cell – plays a major role in tumor rejection and releases small particles of proteins that cause the target cell to die
+ Dendritic cell – helps with the activation of the rest of the immune system through being antigen-presenting cells (APCs)
Mutations
+ Foxn1nu – has non-functional T cells, functional B cells and functional NK cells
+ Prkdcscid – has non-functional T cells, non-functional B cells and functional NK cells
+ Lystbg – has functional T cells, functional B cells and non-functional NK cell function
+ Btkxid – has functional T cells, non-functional B cells and functional NK cells
Methods
+ Xenograft – cells, a tissue, or an organ that is transplanted from one species to another species. For example, a human cell line is
transplanted into a mouse model.
+ Allograft – cells, a tissue, or an organ that is transplanted into the same species. For example, a murine cell line can be transplanted into
another mouse model.
+ Ectopic – tumor is injected in a place located away from the normal position (e.g. subcutaneous injection of prostate tumor cell line)
+ Orthotopic – tumor is injected at the normal location the tumor would occur in the body (e.g. pancreatic cancer cell line injected
into pancreas)
+ Intravenous – IV injection of tumor cells to create a metastatic model
Oncology Research
+ Tumor – an abnormal growth of tissue (can be benign or malignant)
+ Cell line – a group of cells all coming from the same cell, which contain the same genetic makeup
+ Translational research – determining how the model’s response to antitumor agents correlate to humans
+ Regenerative research – utilizing stem cell therapy to replace damaged cells and tissue
+ Infectious disease research – investigating the facilitation of human-specific infectious diseases, and developing immunization protocols
7
Learn more about our ability to support
your research needs at envigo.com/oncology
This e-book is brought to you by Envigo
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