Immunotherapy Research Applications:
Circulating Tumor Cell Analysis
By 2040, the International Agency for Research on Cancer estimates that the global cancer burden
will grow to more than 27.5 million new cancer cases and 16.3 million cancer deaths.1 Fortunately,
scientific tools for studying, detecting, monitoring, and treating cancer are also on the rise.

Immunotherapy 101
What Are Immunotherapies?
Immunotherapies harness the inherent ability of the human immune system to fight cancer from within. They can use multiple
different strategies to help the immune system recognize cancer cells and prime it to launch effective attacks on tumors.

Types of Immunotherapy

Monoclonal Antibodies

Cytokines

Monoclonal antibodies (mAbs) can be designed tobind to specific proteins on cancer cells, labelingthem as targets for the immune system’s attack cells.
Checkpoint inhibitors are a type of immunotherapy
that are based on mAbs. Immune checkpoint
inhibitors stop the immune system from turning off
before cancer is completely eliminated.

Cytokines are naturally occurring proteins that
activate the immune system. By artificiallyintroducing higher cytokine levels, scientists cancause a patient's immune cells to attack cancer cells
more aggressively.

Vaccines

CAR T-Cell Therapies

Vaccines can be used to prime the immune system
to attack cancer cells using the same principles used
to fight infectious disease. Anti-cancer vaccines caninvolve introducing cancer cell proteins, genetic
sequences, or other components that help immune
cells recognize cancer.

Chimeric antigen receptor (CAR) T cells are humanimmune cells that have been geneticallyengineered to express a protein that will bind tocancer cells, attacking them and activating otherimmune cells to do the same.

What Cancer Types Respond to Immunotherapy?
Immunotherapies have the potential to treat every type of cancer. The FDA has already approved immunotherapies for many
major cancer types, including breast, lung, brain, kidney, and colorectal cancer, and many more are in development.

Circulating Tumor Cells
What Are Circulating Tumor Cells (CTCs)?
CTCs are cancer cells that slough off a primary tumor andmake their way into the bloodstream and lymphaticsystems. Once in circulation, CTCs may seed secondary
tumors in other parts of the body. In contrast with a moreinvasive and localized solid biopsy from a primary tumor,
liquid biopsy analysis of CTCs can noninvasively provide
representative information about tumor heterogeneity andhow cancer is developing.
CTCs are present in most types of cancer that metastasize.
However, some cancer types show much higher CTC
prevalence in the bloodstream than others (see right graph).
Total numbers of CTCs and CTECs identified for various
disease types (adapted from Hu, B., et al, Front. Oncol. 02
March 2022, Vol. 12 | https://doi.org/10.3389/fonc.2022.821454). Center black lines = medians; green, yellow box boundaries =Kruskal–Wallis H-test interquartile range; gray box boundaries =values within 1.5 interquartile ranges of the median

CTC prevalence in the bloodstream also correlates withcancer severity. As a tumor grows or shrinks, the numberof CTCs in the bloodstream rises or falls proportionately.3
As a result, CTCs can provide crucial information about
each individual’s cancer progression.

Applications of CTC Analysis in Immunotherapy Development and Cancer Research

Prognosis

Monitoring• CTC analysis can provide information that aids
researchers in selecting candidates for clinical trials• Since CTC prevalence changes in accordancewith tumor size, it can be used to monitor tumor
response to treatments• CTC enumeration can be used to create diseasestratification thresholds• CTC enumeration in serial liquid biopsy samples
can be used to monitor patients for relapse inlong-term studies• Downstream genetic analysis of isolated CTCs canenable screening for biomarkers associated withanticipated treatment response

Analyzing CTCs With Celselect Slides™

Although scientists have been isolating
and studying CTCs for decades, legacy
technologies present multiple challenges.

Lack ofSensitivity

Incomplete
Solutions

Slow
Processing
Rate

LegacyCTC CaptureTechnologies

CaptureInefficiency

Low
Throughput

To solve these challenges, Bio-Rad scientists developed
the Genesis Cell Isolation System with Celselect SlidesTM.
Together, these tools offer fully automated captureand enumeration of CTCs from liquid biopsy samples.

Celselect SlidesTM Applications

Enrichment

Enumeration• Capture and retrieval of >80% of CTCs fromliquid biopsies• On-slide immunostaining• Removal of >99% of red and white blood cells• CTC Analysis Software for result reporting• Imaging compatibility with automated microscopes• High viability of retrieved cells

Because they originate from diverse tissues, different cancer types have different sizes of CTCs relative to healthy blood
cells and are generally much larger. Celselect SlidesTM are designed with 56,400 microchambers that trap CTCs while redand white blood cells are washed away. As demonstrated in the graph below, Celselect SlidesTM pore size is optimized
across multiple cancer type CTCs.

Celselect SlidesTM Workflows
The Genesis System and Celselect SlidesTM offer intuitive, customizable workflows that leverage automation to savehands-on time, increase throughput, and limit opportunities for user error. With these tools, researchers can isolate CTCs
and CTC clusters to accelerate biomarker discovery, identify cancer treatment resistance mechanisms, drive personalized
medicine, and more.

Enrichment
Prepare Sample

Capture and Recover Cells

Perform Downstream Analysis

AutomatedScientists can characterize enriched cells using methods such as bulk or single-cell sequencing, digital PCR, fluorescentin situ hybridization (FISH), or flow cytometry, or the cells can be cultured for other in vitro and in vivo techniques.

Enumeration
Prepare Sample

Capture Cells

Immunostain Cells

Image

Create Report

Automated

By immunostaining cells, scientists can identify the number of cells with a given expression profile. The number of CTCs canbe related to the state of a tumor's progression.

Learn more about Celselect SlidesTM for use in immunotherapy development
and other cancer research applications at bio-rad.com/celselect.

1

https://www.cancer.org/research/cancer-facts-statistics/global.html

2

https://www.clinicaltrials.go

3

Alix-Panabières C, Pantel K. Liquid Biopsy: From Discovery to Clinical Application. Cancer Discov. 2021
Apr;11(4):858-873. doi: 10.1158/2159-8290.CD-20-1311. PMID: 33811121.

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© 2023 Bio-Rad Laboratories, Inc.
For research use only. Not for use in diagnostic procedures.
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