Your Comprehensive Guide to Tools for Immuno-Oncology Research
How To Guide
Last Updated: May 30, 2024
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Published: May 28, 2024
Credit: Thermo Fisher Scientific
Immuno-oncology, also known as cancer immunotherapy, is a rapidly growing field that studies the ways in which the body’s own immune system can fight cancer. It has the potential to uncover ways to enable immunogenicity of all types of cancer and facilitate long-lasting, protective immunity against future recurrence.
In this guidebook, you will discover educational resources and solutions for a number of immuno-oncology research approaches, including checkpoint inhibition, CAR T cell therapy, and cancer vaccine research.
Download this guide to discover:
- The answers to key questions about immuno-oncology
- Innovative products and techniques
- Time-saving workflow applications
Immuno-oncology
product resource guide
Your comprehensive guide to tools
for immuno-oncology research
Cancer research
Our goal is to support your immuno-oncology
research with a comprehensive range of tools and
technologies that maximize your time, budget, and
data—helping to accelerate your path to discovery
and translation to a clinical application.
In this guidebook, you will discover
educational resources and solutions
for a number of immuno-oncology
research approaches, including
checkpoint inhibition, CAR T cell therapy,
and cancer vaccine research. Learn about
our capabilities, from leveraging innovative
products and techniques to time-saving
workflow applications. We’re committed to
partnering with you for your next breakthrough.
2 I-O product resource guide thermofisher.com/immuno-oncology
Immuno-oncology review 4
Key questions about I-O 4
General I-O workflow 7
Solutions by approach 8
Solutions for checkpoint inhibition 8
Solutions for CAR T cell therapy 12
Solutions for cancer vaccine research 18
Characterize and verify 20
Targeted genetic analysis 20
Targeted gene expression analysis 21
Cell analysis 23
Protein analysis 29
Ordering information 30
Contents
3
Immuno-oncology review
What is I-O?
Immuno-oncology (I-O), also known as cancer immunotherapy, is
a rapidly growing field that studies the ways in which the body’s
own immune system can fight cancer.
Why does I-O research matter?
I-O research aims to develop cancer immunotherapies that go
beyond traditional methods such as surgery, chemotherapy, and
radiation, by enabling the adaptive immune system to recognize
and specifically attack cancer cells while leaving healthy ones
undamaged. I-O research can potentially uncover ways to enable
immunogenicity of all types of cancer and facilitate long-lasting,
protective immunity against future recurrence [1-3]. Recent
breakthroughs in checkpoint inhibition, chimeric antigen receptor
(CAR) T cell therapy, and cancer vaccines illuminate the full
capabilities of the immune system and how it may be harnessed
to combat cancer.
While every immune cell has a key part to play in the landscape
of I-O, T cells and T cell–mediated responses are the focal points
of I-O research today.
What are some of the promising areas
in I-O research?
This handbook will provide an overview of three currently trending
I-O research areas: checkpoint inhibition, CAR T cell therapy, and
cancer vaccines. Figure 1 (adapted from Chen and Mellman [4])
shows where they correlate within the cancer-immunity cycle.
Figure 1. Stages of the adapted cancer-immunity cycle [4] can be impacted by I-O approaches such as checkpoint inhibition, CAR T cell
therapy, and cancer vaccines, as indicated by the icons.
Checkpoint
inhibition
(e.g., B7/CTLA-4)
CAR T cell therapy Periphery
Tumor
microenvironment
Activated T cells circulate
and infiltrate tumor tissue
APCs prime and activate T cells,
initiating immune response
Antigen-presenting cells
(APCs) process antigens and
neoantigens
Upon cell death, tumor
cells release antigens
and neoantigens
T cells recognize and
bind to malignant cells
T cells destroy
cancer cells
Cancer vaccines
Checkpoint
inhibition
(e.g., PD-1/PD-L1)
4 I-O product resource guide thermofisher.com/immuno-oncology
I-O review
Checkpoint inhibition
Immune checkpoints are cell
pathways crucial in maintaining
a normal immune response and
protecting tissues from damage when the
immune system is activated [5,6]. Cancer
cells dysregulate immune checkpoints
and use them as a mechanism of immune
resistance. Understanding the interactions
between tumor and immune cells is one of
the main approaches in I-O research [7,8].
There are natural mechanisms in place
that serve to regulate T cell activity via
interactions with the T cell receptor (TCR).
For example, PD-1/PD-L1 is a coinhibitory
pathway that “masks” cancer cells from
T cell recognition, thereby preventing the attack by T cells.
Antibodies that target the PD-1/PD-L1 pathway and bind to PD-1
suppress its coinhibitory function. The T cells then recognize the
cancer cells and cytotoxic activity commences.
Another example of T cell regulation is the B7/CTLA-4 pathway
that plays a role during the priming of a T cell by an antigenpresenting cell (APC). Blocking of the CTLA-4 receptor by an
antibody allows T cell activation, resulting in an anticancer
immune response.
There are multiple costimulatory and coinhibitory receptor–ligand
interactions between APCs and T cells. For T cell activation
or suppression, T cells must recognize their cognate antigens
through TCRs and then respond to costimulatory (for activation)
or coinhibitory (for suppression) receptor–ligand interactions,
examples of which are shown in Figure 2 [6,9].
Adoptive cell therapy (ACT) and CAR T cell therapy
ACT targets the immune system, enabling the body’s
natural ability to fight the cancer, instead of directly
targeting the cancer itself. This is accomplished by
genetically modifying a subject’s own T cells to target antigens
selectively expressed on cancer cells [10,11]. Successful
applications of ACT include:
• Tumor-infiltrating lymphocytes (TILs) are taken from tumor
tissue, modified ex vivo, and infused in activated form back
into the body to re-infiltrate the tumor and attack tumor cells.
• CAR T cells are generated from the body’s own T cells
and are engineered to express antibody-like chimeric
antigen receptors for targeting specific cancer cells
via surface proteins or intracellular proteins, inducing
anticancer attack (Figure 3).
Costimulatory checkpoint Coinhibitory checkpoint Antigen-presenting cells
T cells
Antigen-presenting cells
T cells
PD-L1 (B7-H1)
PD-L2
PD1
B7-H3 (CD276)
B7-H4 (VTCN1)
4-1BB L (CD137L) HVEM
OX40L (CD252)
GAL9
?
BTLA (CD272)
TIM3
?
MHC II
LAG3
? PD-L1 or PD-L2
CD28
ICOSL (B7RP1)
OX40 (CD134)
CD80 or CD86
ICOS (CD278)
4-1BB (CD137)
CD27 CD70
PVR (CD155)
CD40L (CD154) CD40
IDO
CTLA4 (CD152)
CD80 or CD86
GITR (CD357) GITRL
CD30 CD30L (TNFSF8)
LIGHT (CD258)
DR3
CD96
Nectin-2 (CD112)
TL1A
VISTA (B7-H5)
?
?
DNAM1 (CD226)
B7-CD28 family TNF/TNFR superfamily
PVR (CD155)
TIGIT
Others
Nectin-2 (CD112)
Unknown
VISTA (B7-H5)
Figure 2. Multiple costimulatory and coinhibitory receptor–ligand
interactions between APCs and T cells. One important family
of membrane-bound molecules that bind both costimulatory and
coinhibitory receptors is the B7-CD28 family (purple boxes); all of the B7
family members and their known ligands belong to the immunoglobulin
superfamily. Another major category of signals arises from tumor
necrosis factor (TNF) family members (green boxes), which regulate the
activation of T cells in response to cytokines.
I-O product resource guide thermofisher.com/immuno-oncology 5
A closer look: CAR T cells
The TCR participates in the activation of T cells [2].
Its stimulation is triggered in response to cells expressing major
histocompatibility complex (MHC) molecules with an antigen.
Tumor-specific TCRs can be genetically engineered to recognize
specific cancer cell populations. TCR technology is unique as it
recognizes both intracellular and cell surface proteins, conferring
a broad array of antigen targets. Limitations include patientspecific human leukocyte antigen (HLA) restrictions and the lack
of unique tumor-specific antigens.
CARs are fusion proteins combining intracellular T cell
components and extracellular antigen-recognition domains
from a monoclonal antibody [2,10,11]. They can be constructed
by linking the variable regions of the heavy and light chains of
the antibody to intracellular signaling chains (such as CD3-zeta,
CD28, and 4-1BB) or other signaling factors. T cells that are
engineered to express CARs are not limited by HLAs, since a
CAR molecule recognizes an intact cell antigen on the surface
of a cancer cell. However, they are limited by their inability to
recognize mutated intracellular proteins.
Cancer vaccines
Vaccines represent another important I-O research
area aimed at enabling the immune system to
recognize cancer as a threat. This method is antigenbased, relying on the ability of the immune system to recognize
the protein to induce the immune response. Scientists endeavor
to identify new tumor-associated antigens, called neoantigens,
released within the tumor microenvironment [12]. This aids in
understanding how tumors form and spread, which informs the
development of vaccines. Another method called dendritic cell
(DC) therapy utilizes tumor fragments to activate extracted DCs.
This activation turns DCs into APCs, which are then infused
back into the subject to induce a secondary immune response,
including antibody production [12]. Finally, new combination
therapies and personalization methods are also being studied to
further enrich the capabilities of anticancer immunity.
Figure 3. CAR T cell engineering involves genetically modifying an individual’s own T cells to target antigens selectively expressed on
cancer cells.
PD-L1
PD-1
CAR
T cell
Tumor cell
6 I-O product resource guide thermofisher.com/immuno-oncology
I-O review
CAR T cell therapy
Page 12—Find tools that
span the entire workflow,
from T cell isolation and
activation to cell engineering and
expansion, including scalable solutions
to help get you from basic research to
the clinic.
Cancer vaccines
Page 18—Find transfection
solutions, gene-toprotein services, and
genomic biomarker tools to develop
vaccine therapies.
General I-O workflow
Thermo Fisher Scientific offers many research platforms and
products to help you better understand the interplay between the
immune system and cancer. Expand experimental capabilities
I-O
Clinical
immunotherapy
Cancer research
Key approaches
Figure 4. A growing focal area within cancer research, I-O encompasses a robust workflow. This starts with the biomarker discovery phase,
continues into further research on targets of interest, including contextual studies within model systems, and finally may conclude with characterization
and verification. This workflow is applicable across different approaches within I-O, including checkpoint inhibition, CAR T cell therapy, and cancer
vaccine research.
Biomarker discovery Targets Modification of
model systems
Characterization and verification
Checkpoint inhibition
Page 8—Find workflow
tools for genomic biomarker
discovery, verification, and
protein expression, as well as immune
checkpoint analysis by antibodies
and assays.
I-O review
with our instruments, assays, and reagents to accelerate the
development of the cancer immunotherapies of tomorrow. In the
following chapters, explore our solutions by approach (Figure 4).
I-O product resource guide thermofisher.com/immuno-oncology 7
Checkpoint
inhibition
(e.g., B7/CTLA-4)
CAR T cell therapy
Tumor
microenvironment
Periphery
Activated T cells circulate
and infiltrate tumor tissue
APCs prime and activate T cells,
initiating immune response
Antigen-presenting cells
(APCs) process antigens and
neoantigens
Upon cell death, tumor
cells release antigens
and neoantigens
T cells recognize and
bind to malignant cells
T cells destroy
cancer cells
Cancer vaccines
Checkpoint
inhibition
(e.g., PD-1/PD-L1)
Genomic biomarker discovery and verification tools
• Applied Biosystems™ Clariom™ D Pico assays—Get
a deep view of the transcriptome to rapidly discover novel
biomarkers. Analyze coding and long noncoding RNA as well
as alternative splicing events from as little as 100 pg of total
RNA with this microarray-based solution.
• Applied Biosystems™ Clariom™ S Pico assays—Discover
gene-level analysis of well-annotated genes across the
transcriptome from as little as 100 pg of total RNA. Quickly
identify important gene-level signatures and pathways and
screen large numbers of samples with microarray-based highthroughput, automated formats.
• Applied Biosystems™ TaqMan™ Array Human Immune
Response Plate—Utilize a 96-well plate for quantitative gene
expression analysis. Accurately analyze genes from 9 classes
of immune system functions, including cell surface receptors,
transcription factors, cytokines and cytokine receptors, and
cell cycle and protein kinases.
Solutions for checkpoint inhibition
Find out more at thermofisher.com/checkpointinhibitor
Identifying and validating predictive biomarkers for checkpoint
immunotherapy is important to optimize therapeutic benefit,
minimize toxicity risk, and guide combination therapy
approaches. Discover a wide variety of solutions, from
• Applied Biosystems™ TaqMan™ Array Human Immune
Panel—Get quantitative gene expression analysis of a
comprehensive set
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