For years, the relative abundance of particular proteins has been estimated from mRNAs in bulk tissue samples. Single-cell transcriptomics allowed a more pinpointed inference of protein levels based on detected RNA transcripts. But now the nascent field of single-cell proteomics promises direct measurements of the proteins within or secreted from individual cells. Here is a look at the emerging field of single-cell proteomics and recent applications of its technologies to combating SARS-CoV-2, the virus responsible for the COVID-19 pandemic.
IsoPlexis offers the IsoLight platform for highly multiplexed single-cell proteomics of over 30 cytokines released from individual cells. Known as functional phenotyping, the results of IsoPlexis’s Single-Cell Secretome solution allow researchers to take proteomic snapshots of individual immune cells by measuring the many cytokines they secrete.
Applications of their technology are helping to predict which patients might respond to particular therapies for blood and solid tumor cancers as well as infectious disease, says Sean Mackay, co-founder and CEO of IsoPlexis. “Our technology allows clinical researchers to uniquely pinpoint each single cell’s functional phenotype that influences the course of therapy, and identifying these cell subsets has helped predict durable and quality immune response correlating to outcome preclinically and in the clinic,” he says.
Single-cell proteomics firm IsoPlexis said Tuesday that it has received a $2 million Small Business Innovation Research (SBIR) grant from the National Institute on Aging of the National Institutes of Health.
The Phase 2 grant is for work the company is doing to analyze the proteomic responses of trafficking leukocytes in patients with Alzheimer’s disease and related neurodegenerative conditions.
IsoPlexis is developing assays on its IsoLight system for detecting the inflammatory immune response generated by cells including peripheral monocytes, highly polyfunctional secretomic T cells, and microglia and exploring whether these profiles could be used for diagnosing and monitoring inflammatory neurodegenerative diseases.
Vaccine development can be daunting. The overarching goal to create long-lasting immune protection requires an in-depth understanding of the immune system’s response to an infectious agent, immune monitoring to determine and predict the building of the protective response, as well as cytokine-level monitoring for potential toxicities related to cytokine storms.
GEN spoke to five leading researchers to hear their views and strategies on infectious disease research and vaccine development.
Merck & Co. has begun working with the non-profit Institute for Systems Biology and a consortium of companies to investigate the molecular mechanisms behind the novel coronavirus, in a bid to identify new targets for medicines and vaccines. Late last month, the ISB launched a study with health workers from Swedish Medical Center, also based in the institute’s hometown of Seattle, to explore why certain COVID-19 patients die or require intensive care while others may show no symptoms at all. Both the ISB and Swedish are part of the Providence St. Joseph Health network.
Other participants in the study include health workers within Providence St. Joseph Health and the Swedish Medical System, as well as collaborators from Stanford University, IsoPlexis, Adaptive Biotechnologies, 10x Genomics, Metabolon and others.
Merck will provide research funding and work with ISB researchers to find targets for potential interventions, including drugs, antibody therapies and vaccines. The study will initially analyze samples from 200 patients with the potential to expand to 300.
In recent years, developments in single cell and single molecule techniques have allowed proteomics researchers to characterize the body’s immune response with improved depth and resolution.
Much of this research has been focused on immuno-oncology, but as the SARS-CoV-2 outbreak has turned into a global pandemic, a number of companies and researchers in this space have turned their attention to better understanding how patients’ immune systems respond to the virus.
Single-cell proteomics firm IsoPlexis has to date largely marketed its IsoLight platform to researchers doing work on cancer immunotherapy, where it has proved useful for assessing immune cell cytokine production.
Given the apparently important role of overactive cytokine production, the so-called cytokine storm, in COVID-19 deaths, the company is now working with researchers at the Institute for Systems Biology in Seattle to analyze the cytokine production of immune cells taken from COVID-19 patients.
Functional cellular proteomics platform developer IsoPlexis and the Institute for Systems Biology (ISB) said today they will partner to study COVID-19 by mapping functional immune responses at the single cell level. The partners said they plan to carry out research on immune cells from people who have been diagnosed with, or recovered from, COVID-19. IsoPlexis’ single cell functional proteomics platform will be applied on a variety of immune cell types, including various T cells and myeloid cells, in order to map the overall response to the virus. According to IsoPlexis, uncovering functional immune responses using its technologies has led to key breakthroughs in therapies that harness the immune system across disease areas. “Global effort and partnerships are needed to reach an accelerated understanding of COVID-19,” added ISB president and professor James R. Heath, PhD. Speaking with GEN last year, Heath discussed how single-cell functional analyses accelerated development of CAR-T therapies. The analysis of CAR-T cells prior to infusion, he noted, can help researchers anticipate patient response, which also provides feedback usable in the process of manufacturing cells; “You want to control the manufacturing process to optimize the tumor killing properties of the T-cells, while also minimizing factors such as T cell exhaustion. “These single-cell functional analyses have been pretty good across the board at differentiating responders from non-responders, both during the course of therapy and, in some published cases, in terms of analyzing CAR-T-cell products before they are even infused into the patient,” Heath observed. “There are not many other metrics that have yet emerged that give you that type of feedback.”
Single-cell proteomics firm IsoPlexis is collaborating with researchers at the Institute for Systems Biology in Seattle to look at the immune response in patients who have been diagnosed or recovered from COVID-19, with the goal of better understanding what factors are involved in better and worse outcomes. The company’s IsoLight platform is capable of measuring dozens of proteins in single cells and has found a niche within cancer immunotherapy where researchers are using it to look at immune cell cytokine production. The company plans to similarly analyze the cytokine production profiles of immune cells taken from COVID-19 patients, said Sean Mackay, the company’s co-founder and CEO. IsoPlexis also plans to work with the ISB to make bulk measurements of cytokines secreted by patient immune cells, with the goal of better understanding which people may be more susceptible to the “cytokine storm” phenomenon where an overactive immune response causes severe illness or death in certain patients.
IsoPlexis has partnered with the Institute for Systems Biology (ISB) to map functional immune response to COVID-19 at the single-cell level. The group will use IsoPlexis’ single-cell functional platform to analyze immune cells from individuals who have been diagnosed or recovered from COVID-19. The team aims to examine a variety of immune cell types—including various T cells and myeloid cells—to put together a map of the overall response. “Through our unique functional analysis of each cell, we can unlock further understanding of how COVID-19 interacts with the immune system,” Sean Mackay, CEO and cofounder of IsoPlexis, said in a statement. “Cellular immune signatures based on cytokines may be key in understanding and predicting response, and also how to mitigate disease progression.”
IsoPlexis has released two new products for use with its IsoLight cellular proteomics instrument. CodePlex Secretome is a fully automated approach to obtaining highly multiplexed bulk cytokine data that requires five minutes of hands-on time for sample loading. CodePlex Secretome multiplexes more than 30 cytokines, and is modular so users can simultaneously examine as few as eight samples or as many as 64. The new Single-Cell Innate & Myeloid solution detects the functional single-cell differences from innate and myeloid cells by identifying what each cell secretes in a highly multiplexed (32-plus cytokines) manner to reveal the sources of cellular difference through functional phenotyping. It joins other IsoLight single-cell chip applications which allow researchers to visualize single-cell-level data and pinpoint biological drivers.
Unable to be detected by conventional technologies, cellular functional heterogeneity leads to differences in patient response and disease progression. Filling this gap, IsoPlexis’ single-cell functional proteomics is allowing researchers to characterize the full range of extracellular functions (32+ cytokines) per single cell. By exploring, understanding, and characterizing cells based on function, researchers can accelerate therapeutic development by revealing new phenotypes that specifically correlate to individual disease or response states.
In a recent study led by researchers at the University of California, Los Angeles, proteomics firm IsoPlexis demonstrated the capabilities of its expanded single-cell analysis platform. In the work, which was detailed in a paper published last month in Nature Communications, scientists used the company’s platform to profile the cytokines produced by both T cells and natural killer (NK) cells in the blood of melanoma patients receiving adoptive cell transfer (ACT) therapy. IsoPlexis is currently expanding its offerings to target a variety of different immune cell types, said Sean Mackay, the company’s co-founder and CEO. From IsoPlexis’ perspective, the analysis of NK cells is significant in that it demonstrates the ability of its platform to look beyond T cells and to effectively analyze NK cells circulating in patient blood. “This is the first time that has been published,” Mackay said, adding that it marks an important step for the company’s efforts to move into cancer immunology more broadly. The NK cell analysis used the same cytokine chip that IsoPlexis has offered for T cell research. However, Mackay said the company is developing new cytokine chips specific for macrophages and monocytes that will better address those cells’ specific cytokine repertoires. The company is also releasing this quarter a panel aimed at bulk cell analysis of cytokines. While IsoPlexis has focused primarily on single-cell analysis, Mackay said it has received requests from customers interested in doing comparisons of single-cell and bulk cytokine profiles.
Nektar Therapeutics Announces Publication of Two Manuscripts on Lead Immuno-oncology Candidate, Bempegaldesleukin (Bempeg) in Nature Communications
Nektar Therapeutics today announced the publication of preclinical data on its lead immuno-oncology candidate, NKTR-214, bempegaldesleukin (bempeg) in two manuscripts in Nature Communications. Bempeg is an investigational CD122-preferential interleukin-2 (IL-2) pathway agonist designed to provide activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells. The published data demonstrate that bempeg, in combination with immune-based therapies including checkpoint inhibition (CPI), antigen-specific vaccination and adoptive cell transfer (ACT) therapy, enhanced T-cell mediated tumor control by selectively expanding effector T cells (Teffs) over T regulatory cells (Tregs) in the tumor microenvironment. In the second manuscript, published this week in Nature Communications, a research team led by Antoni Ribas, Ph.D. at the UCLA Jonsson Comprehensive Cancer Center evaluated bempeg in combination with adoptively transferred T cell therapy (ACT) in melanoma models. The studies found ACT therapy supported by bempeg increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in the B16 melanoma model.
Therapies that entail removing immune cells from patients and engineering them to recognize and fight cancer have revolutionized the treatment of some blood cancers, but they’ve proven difficult to translate to other tumor types. Researchers at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center believe they’ve hit upon a combination treatment that could help expand the use of cell therapy. The UCLA team is planning future studies to better understand how signaling pathways contribute to the anti-cancer effects they observed in mice given the T-cell combination therapy, they wrote in the study. The synergy they’ve seen so far, they said, “suggests that in patients with cancer, NKTR-214-containing regimens could increase tumor control without exacerbating systemic inflammation.
In a January 2020 Genetic Engineering & Biotechnology News webinar, Leonardo Ferreira, PhD, Postdoctoral Scholar and Jeffrey G. Klein Family Diabetes Fellow at the University of California, San Francisco, and Jonathan Chen, technology co-inventor at IsoPlexis, discussed CAR Tregs and how the IsoPlexis IsoLight single-cell functional proteomics system is crucial in the informed design and development of this next generation of cell therapies. To view the on demand webinar, visit here.
The last decade was an eventful one for proteomics as the field saw a number of advances ranging from new workflows and applications to improvements in instrumentation and bioinformatic innovations. Immunoassay-based methods aimed at measuring relatively large numbers of proteins at the single-cell level also saw significant advances during the decade. This was particularly true on the commercial side, with companies including Fluidigm, NanoString Technologies, IsoPlexis, Akoya Biosciences, Zellkraftwerk, IonPath, and Mission Bio launching tools for single-cell protein analysis during the last decade.
After two-plus decades spent struggling to drive experiment run times down to more manageable levels, a sense emerged this year within the field that this challenge had at last been met. Single-cell proteomic technologies also saw continued growth with a number of new developments in what is becoming an increasingly crowded field. Branford, Connecticut-based IsoPlexis closed a $25 million Series C round that it is using to launch several new single-cell protein assays as well as expand its operations across the US, Europe, and Asia.
Single-cell functional proteomics platform developer IsoPlexis announced this week it has raised an additional $20 million in a Series C round, capital that will enable the company to continue the global expansion of its flagship IsoLight single-cell proteomic analysis platform. According to the company, its technology has been used in a number of different settings including precision drug discovery and biomarker discovery in oncology, to identify proteomic differences that are often undetectable via other methods.
IsoPlexis said today that it has raised an additional $20 million as part of its Series C financing. That follows the $25 million the company announced in May 2019, bringing the total figure for the round to $45 million. The company said it plans to use the funds to drive commercialization of its IsoLight single-cell proteomic system. IsoPlexis has 130 employees and recently expanded its presence throughout the US, Europe, and Asia.
GEN interviews CEO and Co-founder of IsoPlexis, Sean Mackay, who discusses some of the biggest advancements in the field, how IsoPlexis is supporting the industry, upcoming new products, and the company’s vision for the next 5-10 years.
Single-cell proteomics firm IsoPlexis said today it has received a $2 million grant from the National Cancer Institute’s Small Business Innovation Research (SBIR) Development Center. The grant will fund development of methods using the company’s IsoLight system to study protein signaling pathways in single tumor cells, allowing for improved analysis of cancer signaling and tumor heterogeneity.
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.
In this issue of Blood,report that the heterogeneity of personalized chimeric antigen receptor (CAR) T cells has limited the ability to identify product attributes that enhance patient outcomes, but they have showed that by using single-cell analyses, heterogeneity may actually improve clinical outcomes. Single-cell polyfunctional analyses provide a measure of product efficacy that can be used to identify patients likely to respond to treatment and those likely to develop toxicities.
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.