The podcast began with a review of Ultivue’s innovative InSituPlex® staining technology and service offerings enabling key insights into the tumor microenvironment as well as what makes these workflows so unique, by outlining the differences between single marker IHC approaches and other techniques such as FISH and addressing the importance of standardization and reproducibility.
One of the exciting areas of opportunity for integrating digital pathology is the journey from biomarker/drug discovery to drug approval to implementation in clinical practice and then, of course, one arena for future developments in diagnostics is a multiplexing-based companion diagnostic. Dr. Wharton noted that while “I don’t think the field is there quite yet”, we’re instead “at the stage where we’re using the technology to help our customers get a better understanding into simply what they’re seeing in tissue.” Dr. Wharton pointed out that while digital pathology studies are often done on retrospective cohorts, large tissue collections with outcome data present an opportunity to generate and test hypotheses leading to deeper clinical insights.
The podcast finally reviewed other topical areas such as the role of deep learning, AI and integration of more traditional methods such as H&E and ultimately speculated on the possibility of digital pathology as the platform of choice for an integrated clinical diagnostic that incorporates molecular data (e.g. DNA hybridization), multiplexed protein detection, and tissue features derived from methods such as H&E staining. The opportunity that these evolving innovative methods will bring, especially to the arena of immunotherapeutics, will mark significant changes in the field in the coming years.
There’s lots more, to listen to the full podcast:
Ultivue, a leader in advancing precision medicine and unique image analysis solutions by accelerating tissue biomarker discovery and validation develops unique assays for use in multiplex immunofluorescence imaging and analysis. Its proprietary InSituPlex® technology is designed for fast and comprehensive exploration of biologically relevant markers combined with same slide-H&E analysis in precious tissue samples.
“Ultivue’s move and significant expansion at Burlington Biocenter is a strong indication of the company’s continued growth and the unwavering demand from life sciences tenants in the market,” said Kevin Malloy. “Market conditions were extremely challenging during our search as a result of biotech tenants leasing space at record levels. We ultimately secured the ideal space for the company’s evolving laboratory and office needs.”
“Avison Young did an exceptional job strategically navigating a challenging market with limited inventory to procure a space that aligned with our research, development and growth needs,” said James (Bud) Drummey, Vice President of Product and Quality at Ultivue who lead the facility search efforts. “Burlington Biocenter’s cutting-edge, lab-ready facilities and prime suburban location provided the space and efficiency for us to maximize productivity while acquiring and retaining top talent.”
About Avison Young
Avison Young creates real economic, social and environmental value as a global real estate advisor, powered by people. As a private company, clients collaborate with an empowered partner who is invested in their success. Avison Young is a 2021 winner of the Canada’s Best Managed Companies Platinum Club designation, having retained its Best Managed designation for 10 consecutive years.
For more information, visit avisonyoung.com
About Ultivue
Ultivue provides pathologists, researchers and scientists with multiplex biomarker assays for tissue phenotyping and digital pathology. Its proprietary InSituPlex® technology enables advanced exploration and interrogation of tissue samples for precision medicine research. These highly customizable solutions and scientific consultative approach strengthen and accelerate biomarker discovery and drug development programs. For more information, visit ultivue.com.
Ultivue
James Drummey
Vice President of Product and Quality +1.617.250.7603
Due to their heterogeneous nature, tumor tissues vary considerably in their microenvironment, and the existence of a variety of cell types can dramatically influence the ability of the immune system to infiltrate and attack tumor cells. analysis can be used to characterize the immune cell repertoire, identify various cell populations in the microenvironment. Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types addressed in the tumor microenvironment and studies have shown that this TAM population is in a state of constant transition between two forms referred to as M1 and M2 types. M1-type macrophages have anti-tumor effects, which can distinguish tumor cells from normal cells. By identifying tumor cells, expressing e.g. nitric oxide synthase (iNOS) and ultimately killing tumor cells, studies have found that M1 type macrophages exhibit different effects on killing tumor cells. These macrophages can also present tumor-specific antigens to T cells and help in the anti-tumor immunity. Conversely, M2 has the function of removing debris, promoting angiogenesis, tissue reconstruction and injury repair, as well as promoting tumorigenesis and development. The majority of TAMs are of the M2 phenotype (e.g. expressing CD163) and have poor antigen presentation capacity and can suppress the T cell response, importantly therefore the need for selective M2-to-M1 macrophage repolarization has drawn attention for effecting immunosuppression and improving antitumor responses. Recently, a variety of therapeutic agents (e.g., monoclonal antibodies, small molecular inhibitors, and nanoparticles) have been extensively explored for M2-to-M1 macrophage repolarization.
Using a cyclic RGD peptide functionalized and manganese doped eumelanin-like nanocomposites (RMnMels) Liu et. al., 2022 reported a novel combined hyperthermia-immunotherapy against PC3 prostate cancer in mouse models demonstrating that RMnMels could successfully promote M2-to-M1 macrophage repolarization via scavenging multiple reactive oxygen species and remodeling the immunosuppressive tumor microenvironment. Specifically, following near-infrared light irradiation, RMnMels-mediated thermal ablation could destroy the tumor cells directly, but also in part using a tissue immunofluorescence assay addressing CD163 and iNOS, RMnMels could elicit the release of damage associated molecular patterns and tumor-associated antigens, provoking robust tumor immunogenicity and strong antitumor immune responses. I’ll be following with interest the future developments of RMnMels and other therapeutic nanoplatforms for immunomodulation and enhanced antitumor immune responses.
Advances in multiplexed immunofluorescence techniques have helped tremendously to visualize biologically and prognostically relevant macrophage subpopulations in the tumor microenvironment from FFPE sections. If we now think back to Hitchcock’s approach for success as simplicity in the story and guiding with relevant information, Ultivue’s InSituPlex® multiplex immunofluorescent (mIF) technology embodies these sentiments by enabling a streamlined biomarker detection and tissue analysis. The workflow begins by incubating a tissue slide with a mixture of barcoded antibodies for multiplex target labeling. Bound antibody barcodes are then amplified to increase the sensitivity of complimentary fluorescent probe hybridization. Bound probes are then imaged to provide a view of targeted cells like macrophages populations and their cellular interactions within a spatially preserved tumor microenvironment. Importantly researchers benefit from the simplified workflow and availability of Ultivue’s flexible options for pre-optimized off-the-shelf panels or custom panels that include up to 8 relevant application focused targets e.g., a TAM panel.
While the complexities of the tumor microenvironment still remain an area for great discovery, in immunotherapy research perhaps focus on the murderous M1 macrophages and their sidekicks may be the hero ending we’re all looking for.
Contact Ultivue today to see how InSituPlex mIF technology can drive discovery in your tissue biology application.
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