How single cell proteomics data can drive CAR-Treg-based therapies—an interview with Leonardo Ferreira
Leonardo Ferreira, a postdoctoral fellow at the University of California, San Francisco, discusses the application of single cell proteomics data to understanding the function and therapeutic potential of genetically engineered regulatory T cells.
Understanding T-cell polyfunctionality: How single cell proteomics data drive CAR-T cell therapy research and development
Vladimir Senyukov, Director of BioAnalytical Development at Precision Biosciences, talks about investigating T-cell cytokine production using single cell proteomics in order to unlock the therapeutic potential of allogeneic CAR-T cells.
IsoPlexis reported today that it has launched IsoSpeak software for automated on-site analysis and advanced, functional, single-cell mapping. “People see well-published data showing that proteomics can confirm how each sample is performing. This information is critical for developing immunotherapy applications. Until today, most technologies for gathering this data involved much complexity and great difficulty,” explains Mackay. “There are thousands of data points per sample which, in theory, require a lot of informatics and computers to put the data together. Our software takes all that information and those multi-data points and condenses it in your hand in an easy-to-use fashion. Getting the data is quick, and once the run is done, all those data visualizations are able to be manipulated by users on the same day.”
IsoPlexis’ New Software & Applications Pave the Way for Novel Functional Understanding of Single-Cell Immune Activation and Further Application Expansion
IsoPlexis also expanded its applications with new IsoCode Chip products, including the murine cell Single Cell Polyfunctional Strength solution to open up a variety of previously published insights in the pre-clinical realm. Additionally, the Single Cell Polyfunctional Inflammation solution helps discover and target important inflammatory cell types, in high need areas like auto-immune disease, neuro-inflammation, and immune related adverse events.
We explore how automated cell-manufacturing platforms, such as the Miltenyi Biotec CliniMACS Prodigy®, and single-cell technology from IsoPlexis can be used to produce and assess the functional biology of next generation cell therapy products. With a deeper understanding of cellular function by characterizing the functional cytokines from each single cell, scientists can analyze how the CAR-T cells are likely to impact the immune system, which can translate to how the therapy would affect patient outcome.
Studies indicate IsoPlexis’ Polyfunctional Strength Index (PSI) has the potential to be a clinically relevant biomarker of early immune checkpoint inhibitor response
IsoPlexis, which recently received an NCI grant, reports that it has published a technology note with Miltenyi Biotec in a co-marketing agreement.
IsoPlexis said today that it has entered an exclusive agreement with BioStream to distribute its single-cell protein analysis products in Japan.
An urgent need exists for novel detection strategies to better understand mechanistic function and efficacy at the single-cell level in a way that correlates to clinical outcomes. Population level studies do not provide the necessary insight into immune response heterogeneity at the single-cell level. IsoPlexis’ single-cell proteomics systems address this challenge by connecting each immune cell to the many cytokines they secrete, which orchestrate the immune system.
There are no currently well-defined methods to predict or characterize adverse effects, such as severe cytokine release syndrome (CRS) or neurotoxicity. Although circulating cytokine levels in blood are monitored, often that is too late, and drugs, such as IL-6, cannot prevent the patient’s death. In addition, the CAR T-cell infusion product may contain some cells with bizarre functions. IsoPlexis’ technology can comprehensively evaluate the cells with almost no bias, so you get a full portrait of the whole infusion product, even small subsets of the cells with bizarre functions.
Single-cell suspensions don’t present spatial context like needle biopsies do, but the cytokines each individual cell produces still tell a compelling story. For example, cytokine secretion profiles correlate with, and can help predict, clinical outcomes in immunotherapy, said Will Singleterry, PhD, director of business development at IsoPlexis. To back this assertion, he presented data from the company’s many collaborations.
Researchers and clinicians urgently need new approaches to understand the functional profile of cell therapy products to accelerate discovery and development, to achieve manufacturing consistency, and to predict which patients will derive the most value from these drugs while minimizing side-effects. IsoPlexis’ Polyfunctional Strength Index (PSI™) can be utilized to address these challenges, in particular to provide metrics that uniquely relate the CAR-T cell product response to in vivo preclinical and clinical outcome measures.
Unlike a small molecule or antibody that always has the same structure, each time an autologous cell therapy is developed the starting material comes from a different patient, making it virtually impossible to reproducibly develop an identical “drug”. Having the ability to drive better outcomes by profiling the complete function of each cell would be a significant advantage for bioengineers—a challenge the IsoPlexis single-cell proteomic system has been designed to address.
James Heath, PhD., is president and professor at the Institute for Systems Biology in Seattle. He also has the position of Professor of Molecular and Medical Pharmacology at UCLA, and he has directed the NCI-funded NSB Cancer Center since 2005. GEN recently spoke with him on current issues and future trends regarding CAR T-cell therapeutics.
There is an urgent need to characterize the potency and efficacy of CRISPR-Cas9-modified inducible pluripotent stem cell-derived natural killer cells for preclinical cancer immunotherapy research. IsoPlexis’ single-cell proteomics system addresses this challenge by connecting each immune cell to cytokine secretion and thereby correlating them to in vivo outcome across a range of disease areas.
In work presented at the recent American Association for Cancer Research annual meeting, they found that T-cell cytokine production predicted patient response.
“We are pleased to lead the financing of IsoPlexis, an emerging leader in single cell analysis, which is catalyzing research in immunotherapy as well as a number of other high value applications,” Chris MacGriff of Northpond Ventures said in a statement.
The Branford, Connecticut-based company said that it will use the funds to commercialize its IsoLight platform for use in quality control and guidance of CAR T therapy.
As IsoPlexis prepares to take its production to the next level in 2018, two science news publications have honored the company for technology that tailors optimum treatments for cancer patients. The Scientist magazine named the company’s IsoCode chip and IsoLight platform, an all-in-one system that reads the individual cells of tumors, as the Top Innovation of 2017. One week later, FierceBiotech named the same system the 2017 Fierce Innovation Award for Technology Innovation.
The work was part of a larger study looking at the effectiveness of ACT in combination with the cytokine agonist NKTR-214. The study, led by Antoni Ribas, director of the tumor immunology program at UCLA’s Jonsson Comprehensive Cancer Center, found that the ACT-NKTR-214 combination improved the induction of cytotoxic T cells and increased their polyfunctionality, indicating that addition of NKTR-214 could boost the performance of ACT. NKTR-214 is produced by San Francisco-based biopharma company Nektar Therapeutics, which also participated in the study. “The finding in a preclinical model that the IsoPlexis assay can detect a remarkable increase in polyfunctionality in tumor-infiltrating lymphocytes recovered from tumors of mice treated with NKTR-214 compared to IL-2 is the most conclusive data we have obtained in this model system,” said Ribas.
IsoPlexis has been Recognized with Pharma Tech Outlook’s Cover Story for the Top 10 Analytics Solution Providers in 2018
The award focuses on IsoPlexis’ IsoSpeak software suite’s ability to clarify results, reports, and associations from large, complex patient data sets, thereby delivering leading biopharma and clinical researchers better data by which to determine effective cancer immunotherapies.
Research recently published in the journal Blood — conducted in a collaborative effort with Kite Pharma, a Gilead company — demonstrates a significant association between the functionality of an anti-CD19 CAR-T cell product before treatment, as defined by IsoPlexis’ Polyfunctional Strength Index (PSI), and the objective response in patients with non-Hodgkin lymphoma (NHL). “The results highlight the potential to predict whether cancer patients will respond to CAR-T cell therapy before treatment, as well as to improve both pre-infusion product potency testing and guide cell product optimization.”
U.S. Senator Chris Murphy is Highlighting IsoPlexis of Branford, Connecticut, as “Murphy’s Innovator of the Month” for their Work Combating Cancer
“I’m proud to launch my series with IsoPlexis as the inaugural awardee. The folks at IsoPlexis are doing breakthrough work to make cancer treatments more effective and stop this deadly disease in its tracks—that’s something to celebrate.”
Congratulations to IsoPlexis director and co-inventor Dr. James Heath, who was named President of the Institute for Systems Biology
“I am extremely honored to assume the position of president of ISB. It is also tremendously humbling to follow in Lee Hood’s footsteps. Lee is a giant of science, and he has changed the face of modern biology. Through scholarship, innovation, and an outstanding faculty, he has also built ISB into the world leader of systems biology. I can’t wait to begin working with ISB faculty to help build an ISB for the future.”
As described in the abstract of this clinical biomarkers presentation, the IsoCode platform uncovered that polyfunctional anti-CD19 CAR T cells determined by single-cell multiplex proteomics associated with clinical activity in patients with advanced non-Hodgkin’s lymphoma. The single-cell Polyfunctional Strength Index (PSI) of patient CAR T cells, measured on the IsoCode platform, showed a statistically significant association with objective response to CAR T therapy.
IsoPlexis Research, in Collaboration with Oncology Specialist Kite Pharma, Offers Hope for Targeted CAR-T Treatment
US-based biotech firm IsoPlexis has presented findings from research using the company’s precision engineering platform, called IsoCode. The data show the potential to predict whether cancer patients will respond to CAR-T cell therapy prior to treatment, as well as to improve both pre-infusion potency testing and cell product design.
“Through this research, we were able to highlight the important role a functionally versatile subpopulation of CAR T cells may play in the fight against cancer, leading to new ways to characterize and optimize T-cell products,” Adrian Bot, MD, Kite’s vice president, Translational Medicine, said in a statement. “These insights were made possible by using the IsoPlexis technology.”
The licensing deals, mergers and acquisitions, and excitement at events such as ASCO in the last couple of years, have of course come in combination with the impressive data that clinical trials are yielding, notes Sean Mackay, the chief executive of IsoPlexis. Its partners include the cancer immunotherapy specialist, Kite Pharma. “The reason there is such a high potential is rooted in the data,” Mr Mackay says.
Omics firm IsoPlexis is developing an automated version of its single-cell analysis platform for use in large clinical trials of CAR-T therapies for blood cancers. The Branford, Connecticut-based company is using a $1.8 million grant it received this summer from the National Cancer Institute’s Small Business Innovation Research program to fund development of the automated system.
IsoPlexis, a Branford medical technology company, developed some highly advanced hardware and software that allows oncologists to essentially read the information inside a cancer patients cells to see whether they would react well to immunotherapies
That means before treating a patient, doctors would be able to tell whether the immunotherapy would be effective and whether it would cause unpleasant side effects.
A Branford life sciences company is working to take the guesswork out of cancer treatments with technology that may predict how patients will respond to drugs before being exposed to them. IsoPlexis is developing a system that analyzes patients’ tumors cell by cell to determine how effective or toxic a treatment would be and to help guide doctors’ decisions about mixing different cancer therapies.
This new single-cell technology allows researchers to characterize cells based on the proteins they secrete—as many as 42 different cytokines, chemokines, and other molecule types at once. “The IsoLight single-cell technology, with its ease-of-use, has the potential to impact cancer research for both biomarker discovery and patient monitoring.”
The Life Sciences Innovation Report showcases outstanding innovation that is driving improvements and transforming the industry. “Our ability to measure a lot more functional data per individual patient immune cell has provided a pathway to understanding how immunotherapy works, said Sean Mackay, Co-Founder and CEO of IsoPlexis. Mackay said there are three elements that make IsoPlexis fierce; its thought leadership in technology that stems from the company’s scientific founders and advisory board; a very strong technology platform; and its employees. “All of those elements allow us to maintain our ferocity.”
A UCLA study in collaboration with the California Institute of Technology (Caltech) shows that skin cancer cells could be chemically changed from within to reflexively alter gene expression patterns and intracellular pathways, which allows the cells to become resistant to targeted drugs. The UCLA-Caltech team conducted functional proteomics analysis of single melanoma cells, using a microfluidic single-cell barcode “lab on a chip” to determine how cellular responses varied to BRAF inhibitors.
Researchers at this Center have applied single cell proteomics studies towards understanding patient responses to immunotherapy in clinical trials. This technology has been translated into the commercial sector for cancer immunotherapy applications by IsoPlexis, a company co-founded by former NSBCC postdoc Dr. Rong Fan (now on the faculty at Yale), and with scientific support from NSBCC Project Lead Dr. Toni Ribas.
A team led by researchers at the California Institute of Technology and the University of California, San Diego, has used single-cell phosphoproteomics to detect changes in protein signaling linked to the development of drug resistance in glioblastoma.
The research was led by James Heath, co-director of the UCLA Jonsson Comprehensive Cancer Center’s Nanotechnology Program. Heath is the founder and a board member of IsoPlexis, a company that is seeking to commercialize the technologies used in the study.
Kicking Genomic Profiling to the Curb: How Re-wiring the Phosphoproteome Can Explain Treatment Resistance in Glioma
In this issue of Cancer Cell, Wei et al. (2016) identify adaptive re-wiring of signaling nodes in glioma as major mechanisms of treatment resistance without genome-wide mutations.
$5.75 million was raised by IsoPlexis according to information filed with the SEC. The company has raised an estimated total of $11.25 million via private unregistered security offerings.
Ironwood Capital Connecticut, a unit of Ironwood Capital, announced an investment in IsoPlexis, a venture-capital funded life sciences company developing a diagnostic platform to measure cellular immune response in patients.
A team of researchers at Yale University have invented a novel microdevice capable of detecting 42 unique immune effector proteins, a record number for a single-cell protein secretion assay; using the device, the team was also able to demonstrate that a phenotypically identical cell population still exhibits a large degree of intrinsic heterogeneity at the functional and cell behavior level.
Yale Spinout IsoPlexis Raises $2.4M for “Cellular Fingerprinting” Tech that Analyzes Immune Response
More funding on the books for Yale spinout IsoPlexis: It just raised $2.4 million of a potential $3.8 million round, according to a regulatory filing.
Yale bioscience tools company IsoPlexis recently closed on a $1.25 million Series A round with investments from Spring Mountain Capital, Connecticut Innovations and others.
The company has raised $1.3 million of a $1.7 million early-stage round, according to a regulatory filing.
Connecticut Innovations (CI), the leading source of financing and ongoing support for Connecticut’s innovative, growing companies, today announced a $300,000 investment in IsoPlexis, a life science research tools company located in Branford, Conn.
Spring Mountain Capital, LP, a New York-based investment management firm, announced today that its private equity group structured and led a growth equity investment in IsoPlexis Corporation.
A dream team of Cal Tech and UCLA scientists and doctors have created a treatment that’s giving hope to cancer patients who once had none. The medication was developed by chemistry professor James Heath and his lab at Cal Tech in Pasadena, who work day and night, to help UCLA oncologist Antoni Ribas try to cure his incurable cancer patients.
A new study of genetically modified immune cells by scientists from UCLA and the California Institute of Technology could help improve a promising treatment for melanoma, an often fatal form of skin cancer.
CEO Sean Mackay spoke about the market potential of the product, and how it could add to or improve on existing techniques used in the laboratory. The core of the patent-pending product, he explained, is its ability to perform analysis of isolated single immune cells and of proteins secreted over time.
As analytical technologies have improved over the past decade, it has become clear that cells within the same tissue can differ greatly in how they are behaving at any given moment. Dr. Rong Fan’s team was interested in quantifying the various proteins that individual cells secrete as a function of their health or disease status.
Yale entrepreneurs are upgrading the way scientists monitor the body’s immune system, using the unique protein signature of the human cell itself.
Get the Picture for Personalized Medicine: Microchip Platform Can Create Movie of the Immune System During the Course of Treatment
Dr. James Heath and his colleagues at the California Institute of Technology have developed an enabling microfluidic technology called the Single Cell Barcode Chip (SCBC). The SCBC is currently being used in a melanoma clinical trial where researchers are engineering patients’ immune systems to attack their own cancer.
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—proteins that can reflect the response of the immune system to disease—from single cells.