Unlock the Potential of Your Preclinical Oncology Studies
eBook
Published: June 21, 2023
![oncology studies](https://assets.technologynetworks.com/production/dynamic/images/content/375079/unlock-the-potential-of-your-preclinical-oncology-studies-375079-960x540.jpg?cb=12485360)
Only 5% of all novel anti-cancer drugs succeed in clinical trials. This low success rate reflects the significant barriers that still exist when translating preclinical research into human studies.
Humanized mouse models can help researchers develop more efficacious treatments; they offer a more precise representation of important interactions and provide deeper insights into how a disease responds to treatment.
This eBook explores how humanized mouse models can accelerate the development of novel, safe, and effective oncology treatment
Download this eBook to discover:
- The various types of mouse model available
- The role and application of humanized mouse models in immuno-oncology research
- How to select the most appropriate model for your specific needs
Unlock the full potential of
your preclinical oncology
studies with a humanized
mouse model
Table of Contents
Introduction 3
1. What mouse models are available? 4
2. Humanized mouse models in immuno-oncology 5
BioVolume: Insightful preclinical oncology research 6
Uterine leiomyosarcomas 7
Acute Myeloid leukemia (AML) 8
3. What can humanized mouse models be used for? 9
ICP 9
Cytokine-based immunotherapies 10
ADCC studies 10
CAR-T studies 10
Oncolytic virus efficacy 11
4. Select the right humanized mouse model 12
1. Cell source 12
2. Cell quality 12
3. Mouse strain 12
4. Boosted vs. non-boosted 12
5. Enhance your studies with a partner 13
Benefit 1: Assistance in selecting the most
appropriate model 14
Benefit 2: Access to cutting-edge technologies
to support your studies 15
Benefit 3: Access to dedicated teams of experts 16
Beyond insights: Welfare, speed, and experience 16
6. Unlock the full potential of your preclinical studies 17
7. References 18
transcurebioservices.com 2
The landscape of drug development is notoriously tricky to navigate.
Approximately 90% of drugs fail across all clinical trials — rising
as high as 95% for oncology — despite showing efficacy in
preclinical studies (Figure 1).1
The low success rate indicates
that significant barriers still exist when it comes to translating
findings from preclinical investigations to in-human trials.
One such challenge arises from the limitations of preclinical
models, as many lack the relevancy needed to accurately
represent the human system under study. These issues are
especially pertinent for treatments that target or harness the
human immune system (HIS) to combat cancer, inflammation,
or infection. Traditional preclinical models struggle to accurately
recapitulate the complex interactions between the immune
system and the disease as they occur in humans. Consequently,
the data generated doesn’t provide the critical insight needed
into factors that influence treatment efficacy, such as dosage,
pharmacokinetic (PK), and pharmacodynamic (PD) data.
Humanized mouse models can be the key to more efficacious
treatments. By providing a more precise representation of
important interactions, the models allow researchers to gain
deeper insights into how a disease responds to treatment.
In this guide, we explore how humanized mouse models can
help accelerate the development of novel, safe, and effective
treatments for oncology. We examine:
• The various types of mouse model available
• The role and application of humanized mouse models
in immuno-oncology research
• How to select the most appropriate model for your
specific needs
Finally, we look at the benefits of partnering with a preclinical
CRO specializing in humanized mouse models to further
enhance your oncology research efforts.
Figure 1: Likelihood of approval (LOA) of a drug across different indications from Phase I. [Source: Mullard A, Parsing clinical success rates, Nature Reviews Drug Discovery (2016).1
]
Infectious disease
Haematology
LOA from Phase 1 (%)
Opthalmology
Other
Metabolic
Gastroenterology
Allergy
Endocrine
Respiratory
Urology
Autoimmune
All indications
Neurology
Cardiovascular
Psychiatry
Oncology
0
5
10
15
20
25
30
26.1
19.1
17.1 16.3 15.3 15.1 14.7 13.2 12.8 11.4 11.1
8.4 6.6 6.2 5.1
9.6
Introduction
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Several mouse models exist for conducting oncology research
(Figure 2), each with its own advantages and limitations:
• Syngeneic mouse models enable researchers to study antitumor responses in immunocompetent models, shedding
light on the interactions between immune and tumor
targets. However, these models are limited to the use of
mouse tumor cells, which means that the heterogeneity
of human tumors and the nuances of the human immune
system are not accounted for
• Immunodeficient animals offer an alternative approach
by allowing scientists to observe the effects of a drug on
human tumors directly. However, these models fall short
when it comes to evaluating immuno-oncology therapeutic
approaches, which have proven to be highly effective against
various forms of cancer
• Transgenic mouse models, which express specific human
targets, can only assess a limited number of targets —
constraining the scope of the research
The CD34+ humanized mouse model has emerged as the most
clinically relevant option, as it reconstitutes all human immune
targets and can accurately predict clinical immune response
triggers. What’s more, the model achieves a fully functional
human immune system (HIS) within 14 weeks.
Humanized mouse models offer several advantages for
oncology research, including:
• A deeper understanding of the immune system, which
can lead to the identification of more promising treatment
candidates, and ultimately, reduced development costs and
timelines
• Avoidance of graft versus host disease (GvHD) — a common
drawback in peripheral blood mononuclear cells (PBMC)
engrafted mouse models — in which the grafted immune
system attacks mouse cells. GvHD can compromise animal
welfare and introduce variability in the data. In contrast,
CD34+ HIS mouse models do not develop GvHD, resulting
in higher quality results
• Stable humanization throughout the animal’s lifetime
Owing to the advantages of humanized mouse models, it is
no wonder that many researchers are opting to include them in
their preclinical studies. So, how can humanized mice be used?
Figure 2: A summary of the benefits and weaknesses of different mouse models.
Syngeneic
mouse model
Study of anti-tumor responses
Limited to mouse tumor cells
Does not account for the
heterogeneity of tumors
and nuances of the human
immune system
Immunodeficient
mouse model
Observe drug effects directly
on human tumors
Cannot evaluate immunooncology therapeutic
approaches
Transgenic
mouse model
Expresses specific
human targets
Can only assess a limited
number of targets
CD34+ humanized
mouse model
Presence of all immune cell
types (myeloid cells, T cells,
B cells, NK cells)
No GvHD
Stable humanization
1. What mouse models are available?
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Implanting a mouse
with the tumor, followed by
treatment administration via
intraperitoneal (IP) injection,
intravenous (IV) injection,
or daily gavage
Sacrificing the animal
when the ethical limit is
reached, and if required,
sending the tissues back
to the lab for further
analysis Continual monitoring
of the tumor growth,
with researchers conducting
assessments two to three times
a week to obtain readouts such
as tumor growth kinetics,
tumor engraftment,
and PK/PD data
Humanized mice are extensively used in immuno-oncology studies as they are
robust and can handle various treatments effectively. What’s more, they can
provide valuable insights into tumor growth and treatment response through
tumor measurement. Although tumor growth has traditionally been measured
using calipers, advanced techniques that enable non-invasive monitoring of
tumor progression, such as BioVolume, are becoming increasingly important
tools for more accurate measurements.
The typical use of humanized mice in immuno-oncology studies involves:
2.Humanized mouse models
in immuno-oncology
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5
One of the key benefits of humanized mouse models is the
ability of human immune (HI) cells to interact with the tumor,
allowing researchers to observe more representative antitumor or pro-tumoral effects of a treatment. For instance,
glioblastoma tumors were found to grow faster in humanized
mice due to an abundance of associated macrophages that
promote tumor growth. Conversely, melanoma cells are highly
immunogenic and exhibit slower growth in humanized mice
compared to non-humanized mice.
BioVolume: Insightful preclinical oncology research
BioVolume 3D imaging, a world first, enables the measurement and visualization
of tumor growth in preclinical research, oncology, and drug development animal
models. The non-invasive solution works by reconstructing tumors from 3D, RGB,
and thermal imaging, then uses a machine learning algorithm to automatically
calculate subcutaneous tumor length, height, and width.
Working with a CRO partner that provides BioVolume imaging
can bring multiple benefits to your research, including:
• Increased measurement accuracy
• Enhanced experiment reproducibility
• Improved animal welfare
Figure 3: Illustration showing how BioVolume measures tumor volume accurately and reproducibly.
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Hot tumors vs. cold tumors
In a bid to deliver a tumor model that will unlock the
most insight from your research, TransCure bioServices
has examined more than 50 different cell-line derived
xenograft (CDX)-human tumor models, including:
• B-lymphoma
• Acute myeloid
leukemia
• Multiple lymphoma
• Melanoma
• Colon carcinoma
• Lung cancer
• Ovarian cancer
We have developed a “hot vs. cold” classification to
determine the level of infiltration. Looking at A549
(lung carcinoma), we can see that the tumor is highly
infiltrated — a “hot” tumor. On the other hand, RKO
(colon carcinoma) is much less so, corresponding to a
“cold” tumor.
TransCure bioServices can use this classification, tumor
immune infiltration data, and the mechanism of action
to help you choose the most appropriate tumor model
for your studies.
Uterine leiomyosarcomas
Humanized mice can be used to test treatments in various
cancer types such as uterine leiomyosarcomas (uLMS), classified
by aggressive tumors with poor prognosis. In uLMS, the tumors
are classed as cold tumors — that is, they have minimal T cell
infiltration and are typically unresponsive to immunotherapy.2
Despite being prime targets for immune checkpoint blockade
(ICB), studies proved unsuccessful owing to T cell exclusion
from the tumor microenvironment (TME), which is a major
mechanism of intrinsic resistance to ICB.
To prime tumors for ICB, research has started to focus on
identifying approaches to inflame them. In a recent study,
PI3K/mTOR inhibitors were shown in humanized mice
to induce clonal T cell expansion, eliciting an anti-tumor
response and significant tumor growth reduction.3
Here, the
treatment was shown to convert a cold tumor into a hot tumor
response — a response that cannot be observed in traditional
immunodeficient mouse models.
hCD45
RKO
Colon Carcinoma
103 hCD45/g of tumor
Raji
B Lymphoma
105 hCD45/g of tumor
HCT-116
Colon Carcinoma
105 hCD45/g of tumor
A549
Lung carcinoma
106 hCD45/g of tumor
A375
Melanoma
105 hCD45/g of tumor
U87-MG
Glioblastoma
105 hCD45/g of tumor
22RV1
Prostate Carcinoma
103 hCD45/g of tumor
Figure 4: Tumor classification scale ranging from highly infiltrated (hot) on the left to much less infiltrated (cold) on the right.
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Acute Myeloid leukemia (AML)
Another area where CD34+ humanized mice offer deeper
insights in is identifying potential treatments for cancers that
have liquid tumors, such as those found in AML.
So, how does a typical study look?
Engraftment and tumor induction
To begin, the mouse undergoes engraftment of human
CD34+ hematopoietic stem cells and complete hematopoiesis
reconstitution. Leukemic cells are then administered by
intravenous injection to induce the development of leukemia.
The cells can be sourced from patient samples, established
tumor cell lines or genetically engineered cells. Genetically
engineered tumor cells with reporter genes as luciferase,
mCherry or green fluorescent protein (GFP) are particularly
useful as they allow the easy tracking of the tumor burden
and leukemia spread in the mouse’s body (Figure 5).
Treatment and analysis
Once leukemia is established in
the mice, various treatments can be
administered to study treatment efficacy:
• Chemotherapy
• Targeted therapy
• Immunotherapy
• A combination of treatments
Throughout the study, pathological analysis —
including survival analysis, flow cytometry,
histology, and molecular analysis — can be
performed to monitor the progression of
the disease.
Figure 5: Fluorescence imaging of humanized mice with AML (left) and radiance data after engraftment (right).
[Source: AML-Luc TransCure bioServices internal data.]
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Humanized mouse models can be employed for a wide range
of testing, including the investigation of different mechanisms
of action in cancer treatments. We explore five important
applications here: immune checkpoint inhibitors (ICP), cytokinebased immunotherapy studies, antibody-dependent cellular
cytotoxicity (ADCC) studies, chimeric antigen receptor (CAR)-T
studies, and oncolytic virus efficacy.
ICP
ICP immunotherapies involve drugs that block checkpoint
proteins made up of immune system cells, such as T cells, that
prevent the immune system from attacking cancer cells. Using
humanized mouse models for ICP studies allows researchers
to study both the efficacy and mechanism of action in a single
experiment, while also enabling tumor-infiltrating leukocyte
(TIL) analysis after tumor dissociation.
Case study: Malignant melanoma
Malignant melanoma is an aggressive form of cancer.
Patients with advanced melanoma have a poor prognosis,
with only a 20% 5-year survival rate.
Humanized mice model engrafted with an aggressive form of
the melanoma tumor cell line showed significant tumor volume
inhibition after treatment with an oncolytic virus. An even
greater tumor growth inhibition effect could be observed
in combination with pembrolizumab — pembrolizumab
alone had no effect.4
The data demonstrates that humanized mice could be ideal to
evaluate checkpoint inhibitors strategies — in particular anti-PD1
or anti-CTLA4 approaches, and even combination strategies
with additional immunotherapies that further enhance
the immune response.
3. What can humanized
mouse models be
used for?
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CAR-T studies
In CAR-T cell therapy, T cells are isolated from the spleens
of humanized mice and used to produce CAR-T cells with
the same behavior as normal human T cells. The CAR-T cells
can then be re-infused into animals from the same CD34+
donors to investigate their ability to treat cancers.
Modelling CAR-T therapies in humanized mice enables
researchers to investigate the persistence, efficacy and
immunosafety of CAR-T treatments in the context of a
complete human immune system for deeper insights.
ADCC studies
ADCC is a mechanism of cell-mediated immune defense where
an effector cell lyses target cells. ADCC actively involves NK cells
activation, and so humanized mice with NK-cell boosting are an
ideal model for ADCC studies.
In an internal study performed by TransCure bioServices,
investigators injected A431 melanoma cells subcutaneously into
hIL15-boosted mice. Bi-specific antibodies were directed against
the tumor target and injected at different doses. Notably, NK
cells caused full tumor regression at a high dose.
Cytokine-based immunotherapies
Humanized mice also show great potential in evaluating
targeted immunotherapies, such as those that are cytokinebased. A recent study demonstrated the therapeutic
efficacy of an antibody IL-12 fusion protein (NHS-IL-12) in
a CD34+ humanized mouse model inoculated with human
rhabdomyosarcoma cells.5
Therapy significantly improved
the survival rate and decreased tumor volume. In addition,
the treatment increased tumor mononuclear infiltration,
inducing a high amount of NK cells and macrophages.
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Case study: Blastic plasmacytoid
dendritic cell neoplasm
(BPDCN) treatment
CD123 is an IL-3 receptor alpha chain that is overexpressed in
BPDCN. A recent study used autologous CD34+ humanized
mice to evaluate the immune functions and safety of
CD28/4-1BB CAR-T cells that target CD123.6
Using the mice, researchers were able to investigate
potential toxicity effects by re-infusing CAR-T cells. A low
on-target/off-tumor toxicity against various subsets of normal
cells was found, suggesting that CD28/4-1BB CAR-T cells have
promising therapeutic potential for treating BPDCN
with minimal off-target effects.
Oncolytic virus efficacy
Oncolytic viruses are viruses that infect and directly kill cancer cells by replicating in the targeted cells
and inducing cell lysis. When the virus kills the cells, the cancer cells release cancerous materials — such
as tumor associated antigens — which stimulate the immune response. In addition, oncolytic viruses can
now be genetically modified to deliver therapeutic payloads that will further boost the immunity.
Humanized mouse models can be used in studies investigating oncolytic virus efficacy, as demonstrated
in the earlier case study. Additionally, TransCure bioServices has performed internal studies using
humanized mice engrafted with tumor cells to investigate the tumor growth inhibition effect of a
genetically modified oncolytic virus. Contact us to learn more about these studies.
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4. Boosted vs. non-boosted
Non-boosted models often display lower amounts of myeloid/
dendritic cells and NK cells, with a majority of T and B cells
present. While these are valuable and effective tools for many
studies, some may require better distinction between myeloid/
dendritic and NK cells. In such cases, mice can undergo boosting
to exhibit enhanced differentiation between cell types (Figure 6).
Boosted mouse models are formed through hydrodynamic
plasmid DNA delivery, which allows for more customized
immune system development. Researchers are subsequently
able to tailor their model to their specific needs, as the mice
can be differentiated into the required cell types.
It is crucial to recognize that not all humanized mouse models
are created equal, and choosing a high-quality model is vital for
the success of your research. There are four factors to consider
when selecting the right humanized mouse model — the cell
source, cell quality, the mouse strain, and boosting. Natural
killer (NK)
cells
Myeloid
cells
Dendritic
cells (DCs)
1. Cell source
The origin of the cells used in the model plays a significant role
in its performance:
• Donor blood, as in PBMC mice, which include differentiated
lymphocytes, monocytes, and dendritic cells. Proportions
vary depending on the donor, and these mice often develop
GvHD and show poor development of other immune
populations.
• Cord blood, which is rich in human hematopoietic stem
cells (HSC) and serves as a source of CD34+ cells used to
reconstitute the human immune system. Cord blood offers
better engraftment properties compared to other sources.
2. Cell quality
High-purity CD34+ cells are crucial for high-quality results.
Contamination with other cell types, such as CD4 or CD8 cells
could induce GvHD, lowering animal welfare and interfering with
your findings.
3. Mouse strain
Numerous highly immunodeficient mouse strains are available,
including NSG, NRG, NOG, and BRGS. However, many of these
strains lack human cytokines, limiting the development of the
human innate immune system.7
Some strains, such as NOG, are
genetically modified to express human cytokines to overcome
this limitation.
Figure 6: Plasmid boosting activates CD34+ development into a customizable human
immune system, with the most appropriate proportions of cells.
4.Select the right
humanized
mouse model
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There are many considerations involved when working with
humanized mice, such as selecting an appropriate model and
determining the most suitable studies for your research. It
is important to note, however, that most suppliers will only
provide the mice and not offer any additional services. As a
result, researchers can be left feeling unsupported for their
studies in four significant ways:
1. You must possess a wide range of knowledge across
various fields
2. Labs need to be equipped with an extensive selection
of top-of-the-range instruments for analysis
3. A supplier will not support you in understanding
and interpreting the data generated
4. Humanized mice are more challenging to work with
compared to syngeneic or immunodeficient models,
and a certain level of expertise is necessary to maximize
the benefits of your experiments
To overcome these challenges, you should consider
collaborating with a partner rather than simply relying on
a supplier. A partner can actively support you throughout
all stages of your experiment, from initial discussions and
customized protocol development to executing state-of-theart experiments, data analysis, and comprehensive reporting.
Working with a partner can offer three main benefits, which
we explore in more detail here.
5. Enhance your studies
with a partner
transcurebioservices.com 13
Benefit 1: Assistance in selecting
the most appropriate model
A valuable partner can provide crucial support in choosing
the most suitable humanized mouse model for your research.
They can perform a comprehensive tumor infiltration analysis
of the humanized mouse by dissecting the tumor and preparing
a single cell suspension, then use flow cytometry to obtain a
complete picture of the tumor’s behavior. Subsequently, an
appropriate model can be selected, helping you gain more
relevant insights from your studies.
TransCure bioServices also has access to detailed information
about the infiltration quality in your humanized mouse model.
Given that each tumor has unique characteristics in recruiting
human immune cells, they can help you identify a profile
relevant to your study, ensuring that your research benefits
from the most appropriate model that helps you generate
the data you need.
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Benefit 2: Access to
cutting-edge technologies
to support your studies
A reliable partner will possess a wide range of advanced
technologies to facilitate your research. For instance,
TransCure bioServices offers state-of-the-art services
including flow cytometry and immune profiling,
immunohistochemistry (IHC) histology platforms,
in vivo imaging, and in vitro assays.
Flow cytometry and immune profiling
TransCure bioServices uses the highest-quality instrumentation
with 14 channels each for detecting complex human immune
cell panels. Using the equipment for flow cytometry and
immune profiling: • Enables analysis of immune phenotypes from various
mouse tissues
• Provides insight into biomarkers expressed by tissues/tumors • Enhances understanding of drug mechanisms of action
and therapeutic efficacy
Immunohistochemistry (IHC) histology platforms
TransCure bioServices can conduct morphology studies using
standard or specific labeling/staining techniques, enabling the
investigation of biomarker expression or immune infiltration
through chromogenic and fluorescent IHC.
In vivo imaging
Using in vivo imaging, a partner such as TransCure bioServices
can offer non-invasive detection and quantification of tumors
from their onset to full development. Orthotopic, metastatic
dissemination, and subcutaneous tumor progression can all
be monitored using this technique.
In vitro assays
TransCure bioServices provides a deeper understanding of
drug mechanisms of action through T/B cell stimulation assays
or oncological in vitro assays.
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Experience
The experience of your partner should also be considered.
A partner with extensive experience in the field, such as
TransCure bioServices with their ten years of expertise,
can help you better contextualize your data for greater
guidance in your research.
Speed
Keep in mind that not all mice are immediately available.
Humanized mice, for instance, take 14 weeks to generate.
Limited availability can hinder your studies, reduce flexibility,
and complicate your planning. However, some partners, like
TransCure bioServices, have CD34+ HIS mice ready for use in
studies. Their state-of-the-art facilities can house up to 9,600
mice, and they can supply over 1,000 humanized mice per
month, enabling you to start your experiments and generate
data more quickly.
Welfare
Seek a partner that prioritizes animal welfare. A partner that
does so will be Association for Assessment and Accreditation
of Laboratory Animal Care (AAALAC)-accredited, signifying
that they are dedicated to maintaining the highest standards
of animal welfare.
Benefit 3: Access to dedicated
teams of experts
Working with a partner means gaining access to a diverse
group of specialists with expertise across various fields. A
collaboration, therefore, allows you to tap into the knowledge
you need to design your study and interpret your results
effectively. By leveraging the experience of these dedicated
teams, you can optimize your research outcomes and make
more informed preclinical decisions.
Beyond insights: Welfare, speed, and experience
Although, ultimately, a partner can offer advice, technology and expertise, there are other
considerations that can make them stand out amongst the rest:
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Humanized mouse models provide unparalleled insights into preclinical studies, increasing the likelihood
of successful outcomes in clinical trials and — ultimately — the development of safe and effective
treatments. In particular, humanized models are especially valuable for immuno-oncology research,
supporting studies for:
However, to select the right preclinical model you must consider several factors, such as the method of
generation and cell source. Additionally, although HIS mouse models offer many advantages, they suffer
from limited differentiation of cells. This limitation can be overcome, however, by choosing a boosted
mouse that contains the right proportion of cell types relevant to your study.
To truly unlock the value of your experiments, you should seek a partner, rather than a supplier. By
partnering with an organization like TransCure bioServices, your lab can access a wealth of expertise,
cutting-edge equipment, and comprehensive support from the inception of your experiment to data
analysis. With these resources at your disposal, your lab can make better informed decisions that enable
you to advance only the most promising drug candidates and accelerate your product’s journey to
market.
As an AAALAC-accredited organization with over a decade of experience, TransCure bioServices is
dedicated to providing top-quality humanized mouse models of the highest welfare to enhance your
research and drive innovation in immuno-oncology treatments.
To gain deeper insight from your oncological preclinical studies, get in touch with our team today. • ICP treatments • Cytokine-based therapies • Bi-specific antibodies • ADCC • CAR-T • Cell therapies • Gene-based therapies • Oncolytic viruses
6. Unlock the full potential
of your preclinical studies
transcurebioservices.com 17
Or visit transcurebioservices.com
1 Mullard, A., (2016). Parsing clinical success rates. Nat. Rev. Drug Discov., 15, 447.
Available at https://doi.org/10.1038/nrd.2016.136
2 De Wispelaere, W., et al., (2021). Resistance to Immune Checkpoint Blockade in Uterine
Leiomyosarcoma: What Can We Learn from Other Cancer Types? Cancers (Basel).
2021 Apr 23;13(9):2040. Available at https://doi.org/10.3390/cancers13092040
3 De Wispelaere, W., et al., (2022). Exploiting the Immune-modulatory Effects of PI3K/mTOR
inhibitors to Remodel the Tumor Microenvironment in Uterine Leiomyosarcoma. [Poster].
28th Congress of the European Association for Cancer Research, 2022
4 Kuryk, L., Møller, A-S W., Jaderberg, M., (2018). Combination of immunogenic oncolytic adenovirus
ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized
A2058 melanoma huNOG mouse model, OncoImmunology, 8(2):e1532763.
Available at https://doi.org/10.1080/2162402x.2018.1532763
5 Schilbach, K., et al., (2015). Cancer-targeted IL-12 controls human rhabdomyosarcoma
by senescence induction and myogenic differentiation, OncoImmunology, 4:7.
Available at https://doi.org/10.1080/2162402X.2015.1014760
6 Bôle-Richard, E., et al., (2020). CD28/4-1BB CD123 CAR T cells in blastic
plasmacytoid dendritic cell neoplasm. Leukemia, Dec;34(12):3228-3241.
Available at https://doi.org/10.1038/s41375-020-0777-1
7 Chuprin, J., et al., (2023). Humanized mouse models for immuno-oncology research.
Nat. Rev. Clin. Onc., pp. 192–206. Available at https://doi.org/10.1038/s41571-022-00721-2
References
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