Fluidigm Corporation (NASDAQ:FLDM), an innovative biotechnology
tools provider with a vision to improve life through comprehensive
health insight, today announced the publication of data that
further validate the potential of its mass cytometry technologies,
CyTOF® and Imaging Mass Cytometry™ (IMC™), to provide new
approaches to evaluating cancer therapies in animal models using
human tumor xenografts, potentially identifying which patients are
most likely to benefit from specific targeted cancer therapies.
The research was led by scientists at the Cancer
Research UK (CRUK) Cambridge Institute at the University of
Cambridge in collaboration with the Imaging and Molecular
Annotation of Xenografts and Tumors (IMAXT) Cancer Grand Challenges
Consortium, and the data have been published online in Nature
Communications. This work was funded by Cancer Grand Challenges,
AstraZeneca, a European Research Council Advanced Grant and the EU
Marie Sklodowska-Curie Research program.
Researchers developed a panel of 33 antibodies
designed to detect and differentiate human tumor cells from the
surrounding mouse cells and to detect activation of cancer-related
signaling pathways as well as markers of cell death (including
programmed cell death). The breast cancer mass cytometry (BCMC)
antibody panel was validated in a variety of well-characterized
cell lines and then used to evaluate 53 human breast cancer
xenograft samples capturing the diversity of breast cancers
observed in patients, as previously shown and published in Cell
(Bruna et al., 2016).
This large biobank of human tumor xenografts was
established at the CRUK Cambridge Institute by implanting human
tumor tissue into a mouse and is used as a powerful preclinical
platform to accelerate drug development, allowing high-content drug
screens both in vitro and in vivo.
Xenograft samples were examined via suspension
mass cytometry and IMC to evaluate the presence and distribution of
distinct cell phenotypes in breast cancer tumors and their
surrounding microenvironments. Results of these analyses identified
several unique phenotypic profiles not previously detected using
genomic or gene expression assessments, and also correlated these
phenotypes with breast cancer molecular features.
The study also used drug screening data
generated in the same xenograft platform to correlate
BCMC-determined cellular phenotypes with response or resistance to
specific therapies (caldaslab.cruk.cam.ac.uk/bcape/). These
analyses demonstrated that mass cytometry-based phenotypic
footprints captured distinct features not detected using typical
genetic and genomic evaluations. Examples include the
identification of two distinct types of triple-negative breast
cancers, which are typically aggressive and hard to treat, and the
determination that each group has distinct drug response profiles
when treated with standard of care chemotherapy and targeted
therapies.
Also, a specific cellular architecture (luminal
cell clusters) was identified and was correlated with response to
the PI3K-inhibitors, a class of drugs for which genomic analysis is
a poor predictor of response.
“To date, most studies on tumor heterogeneity
have focused on genetic diversity, and only a handful have
evaluated phenotypic diversity at the protein level. We employed
mass cytometry to identify and characterize core cellular
phenotypes in a large cohort of breast cancer xenografts, part of a
well-characterized preclinical platform in our lab,” said Dimitra
Georgopoulou, PhD, Research Associate at the CRUK Cambridge
Institute and lead author of the publication. “Integrating
phenotypic data with molecular and drug response data from the same
xenografts, we found that phenotypic heterogeneity at the cellular
level is a critical determinant of drug response. This finding has
major implications in both preclinical and clinical efforts in
breast cancer.”
“In the current study we also combined the data
from the suspension mass cytometry approach with Imaging Mass
Cytometry performed on the same xenograft models,” said Dario
Bressan, PhD, Head of the IMAXT Laboratory at the CRUK Cambridge
Institute. “In a previous work (Ali et al., 2020), we also
performed IMC on the primary tumor from which these xenografts were
generated. This was really key to expanding our understanding of
how specific cell phenotypes are spatially distributed and their
clinical relevance. This approach allowed us to map the cellular
phenotypes across mass cytometry platforms and from xenograft to
clinical samples: something quite unique which was never
successfully attempted before.”
An additional key finding from the study is the
demonstration that defined cell phenotypes with different responses
to treatment co-exist within a single tumor. Importantly, this
phenotypic variability does not appear to correlate with genetic
intra-tumor variability. This finding has critical implications for
both preclinical drug screening methods and translational medicine,
suggesting that new combination therapies may need to be developed
in order to address multiple cell types within an individual
tumor.
The authors suggest that mass cytometry could
potentially be used to directly profile biopsy samples from
patients undergoing therapy to more accurately assess their
response to treatment and determine if continued therapy is likely
to provide benefit.
“Our findings open the door to new and
potentially more informative models for evaluating cancer therapy
and for predicting an individual patient’s response to potential
therapies, both of which are important for enabling precision
oncology medicine,” said Georgopoulou.
“This study underscores the importance of global
collaboration among leaders in diverse aspects of cancer research
to yield breakthroughs for the entire oncology research community,”
said Chris Linthwaite, Fluidigm President and CEO.
“Fluidigm is committed to harnessing the power
of our technologies to improve life, and this important study
demonstrates our ability to support cutting-edge preclinical and
translational medicine approaches that truly transform our
understanding of cancer and identify new paths for improving care
and outcome. These data highlight the true benefits of integrating
IMC and mass cytometry to create dual-mode assessments and
workflows that enable efficient generation of rich datasets.”
Learn more:
cancergrandchallenges.org/teams/imaxt
About
FluidigmFluidigm (Nasdaq:FLDM) focuses on the most
pressing needs in translational and clinical research, including
cancer, immunology, and immunotherapy. Using proprietary
CyTOF and microfluidics technologies, we develop, manufacture,
and market multi-omic solutions to drive meaningful insights in
health and disease, identify biomarkers to inform decisions, and
accelerate the development of more effective therapies. Our
customers are leading academic, government, pharmaceutical,
biotechnology, plant and animal research, and clinical laboratories
worldwide. Together with them, we strive to increase the quality of
life for all. For more information, visit fluidigm.com.
Fluidigm, the Fluidigm logo, Advanta,
CyTOF, Imaging Mass Cytometry, and IMC are trademarks and/or
registered trademarks of Fluidigm Corporation in the
United States and/or other countries. All other trademarks are
the sole property of their respective owners. The Advanta™ Dx
SARS-CoV-2 RT-PCR Assay is for In Vitro Diagnostic Use. It is for
Use under Emergency Use Authorization Only. Rx Only. Other Fluidigm
products are provided for Research Use Only. Not for use in
diagnostic procedures.
Forward-Looking StatementsThis
press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, among others, statements regarding applications for and
benefits of Fluidigm products in cancer research. Forward-looking
statements are subject to numerous risks and uncertainties that
could cause actual results to differ materially from currently
anticipated results, including but not limited to risks relating to
the potential adverse effects of the coronavirus pandemic on our
business and operating results; company research and development
and distribution plans and capabilities; interruptions or delays in
the supply of components or materials for, or manufacturing of,
Fluidigm products; potential product performance and quality
issues; intellectual property risks; competition; and reductions in
research and development spending or changes in budget priorities
by customers. Information on these and additional risks and
uncertainties and other information
affecting Fluidigm business and operating results is
contained in Fluidigm’s Annual Report on Form 10-K for the year
ended December 31, 2020, and in its other filings with
the Securities and Exchange Commission. These forward-looking
statements speak only as of the date
hereof. Fluidigm disclaims any obligation to update these
forward-looking statements except as may be required by law.
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Fluidigm
Media:Mark SpearmanSenior
Director, Corporate Communications650 243
6621mark.spearman@fluidigm.com
Investors:Peter DeNardo415 389
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