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Single Cell Barcode Chip (SCBC) enables personalized immune function monitoring: A small sample of a patient’s blood contains both white and red blood cells. The white blood cells are comprised of many different cell types, each of which perform various functions that together represent the activity of the immune system. Single immune cells are captured on the SCBC and their functional behavior read out by recording the levels of a dozen functional, secreted proteins for each captured cell. Image: Young Shik Shin/Caltech
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There's a wealth of health information hiding in the
human immune system. Accessing it, however, can be very challenging, as the
many and complex roles that the immune system plays can mask the critical
information that is relevant to addressing specific health issues. Now,
research led by scientists from the California Institute of Technology
(Caltech) has shown that a new generation of microchips developed by the team
can quickly and inexpensively assess immune function by examining biomarkers from
single cells.
The scientists reported on their technology in an online
issue of Nature Medicine.
"The technology permits us for the first time to
quantitatively measure the levels of many functional proteins from single, rare
immune cells," says James Heath, the Elizabeth W. Gilloon Professor and
professor of chemistry at Caltech and corresponding author of the study.
"The functional proteins are the ones that are secreted by the cells, and
they control biological processes such as cell replication and inflammation
and, specific to our study, tumor killing."
In 2008, Heath led the development of a "barcode
chip" that, using just a pinprick's worth of blood, could measure the
concentrations of dozens of proteins, including those that herald the presence
of diseases like cancer and heart disease. This latest single-cell barcode chip
(SCBC) device builds upon the success of that initial design, which is
currently being utilized in diagnostic medical testing of certain cancer
patients.
The researchers tested the chip by measuring a cancer
patient's response to a type of cell-based immunotherapy designed to target and
kill tumor cells. The only way to know if the therapy is doing its job is to
measure many proteins at the same time from the individual cells that were
targeting the tumor. The SCBC aced this test, generating readouts of a dozen
secreted biomarkers—each of which represented a distinct cell function—and
taking those readings from about a thousand single cells simultaneously.
The team was able to conduct a proof-of-concept study by
looking at samples from a melanoma patient participating in the immunotherapy
trials, and comparing those results to similar samples from three healthy
subjects.
"This technology has the potential to be used
routinely to monitor immune system performance," says Chao Ma, a graduate
student in Heath's lab at Caltech's NanoSystems
Biology Cancer
Center and lead author of
the Nature Medicine paper.
"For example, it can be directly used to evaluate the effectiveness of
certain classes of therapeutics, such as vaccines and other
immunotherapies."
According to Ma, the technology is minimally invasive,
cost-effective, and highly informative. The goal, he says, is to help
physicians closely track the effectiveness of a therapy, and to rapidly alter
or switch that therapy for the maximum benefit of the patient.
"The research fully demonstrates real-life clinical
use of our revolutionary technology," Ma says.
The next step for the team will be to systematically
apply the technology to clinical studies. The researchers have already begun to
test the technology in additional patient populations, and to combine the SCBC
with existing assays in order to get a more comprehensive picture of a
therapy's efficacy.
In fact, the same study that showed the microchip's
efficacy is already helping the researchers better evaluate the specific cancer
immunotherapy trial, from which the patient in the study was drawn. "We
are doing these same types of measurements on similar patients but at a
significantly higher level of detail, and at many time points over the course
of the cancer immunotherapy procedure," explains Heath. "It is
helping us put together a 'movie' of the patient's immune system during the
therapy, and it is providing us with some very surprising but also valuable
insights into how the therapy works and how we might work with our UCLA
colleagues to improve it."
“Application of this technology
provides an unprecedented understanding of the human immune system by allowing
an efficient and multiplexed functional readout of immune responses using
limiting numbers of lymphocytes,” says Antoni Ribas, associate professor of
medicine and physician who led the clinical trial portion of the study at
UCLA's Jonsson Comprehensive Cancer
Center.
SOURCE
