Immunotherapy is a rapidly growing field in cancer treatment, with the aim of modulating tumor immunity to promote tumor-rejection. The development of immunotherapies is a complex process that requires the use of advanced technologies to evaluate the efficacy of compounds and therapeutic antibodies on immune cell infiltration or to screen immune cell populations for use in immunotherapy. In this blog post, we will explore how our in vitro immuno-oncology models can be used to accelerate the drug discovery and development process for immunotherapies. Our expertise lies in transforming tissues into actionable insights and bridging the gap between in vitro assays and in vivo results through the use of best-in-class cell culture models.

Advantages of Our In Vitro Immuno-Oncology Models

One of the key advantages of our in vitro immuno-oncology models is the ability to assess the effect of compounds and therapeutic antibodies on immune cell infiltration. Tumor-infiltrating immune cells are associated with better prognosis for cancer patients, and in vitro assays of immune cell infiltration can be used to evaluate the efficacy of immunotherapies designed to promote the immune cell response to tumor cells. Immunohistochemistry (IHC) is a typical analysis method for labeling T-cells in tumor tissue samples, but it is low throughput and costly. In vitro immuno-oncology models offer a more efficient and cost-effective alternative.

3D Cell Culture Models and Immuno-Oncology Models

Our in vitro immuno-oncology models also allow for the screening of immune cell populations for use in immunotherapy. The 3D cell culture models are more biologically relevant, and allow for proper assessment of immunotherapies designed to promote the immune cell response to tumor cells. The assay involves monitoring the interaction of therapeutics with immune cells in a 2D or 3D assay format. The protocol involves using 3D cell models, grown to approximately 200 μm in diameter, and seeding PBMCs at 4000 cells/well. The markers used for analysis include DAPI (total cell count), CD3, CD8, CD45RO, and other markers available on request.

These patented and proprietary technologies for tissue imaging, tissue processing, and image analysis are critical to the success of our in vitro immuno-oncology models. This approach allows for uniform labeling across thick tissues while preserving histological integrity, and the clearing process is reversible, allowing for further analyses. Specializing in many areas, we differentiate ourselves through our expertise in advanced imaging and image analysis, 3D cell culture models, and AI-enhanced digital pathology.

3D cell culture is a method of growing cells in a three-dimensional environment that more closely mimics the natural in vivo microenvironment. This allows for a more biologically relevant assessment of immunotherapies, as cells grown in 3D models can better replicate in vivo characteristics and interactions with other cells and cellular components. 3D cell culture models offer an excellent format for confirming results of in vitro screening using 2D cells, and for screening hits and lead compounds for potential toxic liabilities. However, determining when exactly to use a 3D cell culture model will depend on the specific research question but will also depend on the cost, throughput and in vivo relevancy of the 3D cell culture model.

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Our advanced imaging and analysis technologies can provide important insights in the drug discovery process for immunotherapies. We offer high content screening for immune modulators, and have experience with immuno-oncology drug discovery and development. These tools ensure that drugs fail faster during the discovery process and that researchers can answer more complex research questions to inform their programs.

In vitro immuno-oncology models are an important tool in the drug discovery and development process for immunotherapies, and we are at the forefront of this field. If you are interested in learning more about our in vitro immuno-oncology models, please reach out to a member of our team to get started today!

In vitro immuno-oncology models are used to study the interaction of therapeutics with immune cells in a 2D or 3D assay format. These models are used to assess the effect of compounds and therapeutic antibodies on immune cell infiltration or to screen immune cell populations for use in immunotherapy. The 3D cell culture models are more biologically relevant and allow for proper assessment of immunotherapies designed to promote the immune cell response to tumor cells. Visikol’s in vitro immuno-oncology models and high content imaging technology can address limitations by providing a method for improving in vitro studies used in drug discovery and development. In this blog post, we will explore how Visikol’s in vitro immuno-oncology models can be used for high content imaging, allowing for more accurate and reliable data for drug efficacy and safety testing. We will also discuss how Visikol’s 3D cell culture models are more biologically relevant and how their high content imaging technology can help researchers and pharmaceutical companies maximize the potential of their immuno-oncology models.

More on High Content Imaging

High content imaging technology is a method of in vitro assay services that allows for the assessment of multiple endpoints simultaneously at a cellular resolution. It utilizes imaging-based endpoints to examine the specific effect of compound treatments on specific sub-populations of cells, as well as providing access to more complex measurements than can be accomplished with traditional assay formats. The data generated from high content imaging is processed using purpose-built image processing pipelines to obtain quantitative data, extracting cell counts, morphological features, colocalization of labels, and computing statistical comparisons between groups simultaneously.

High content imaging technology allows for the assessment of multiple endpoints simultaneously at a cellular resolution, providing richer datasets than traditional assays. This approach enables the interrogation and quantitation of cellular response of disease models to treatments, stimuli, or alterations in protein expression. The use of imaging-based endpoints allows for examination of the specific effect of compound treatments on specific sub-populations of cells, as well as providing access to more complex measurements than can be accomplished with traditional assay formats. Combining these data with machine-learning and informatics expertise, comprehensive reports can be generated that distill the data to its essential components, giving actionable insights about the experiment.

Visikol’s in vitro Immuno-Oncology Models

Visikol’s in vitro immuno-oncology models and high content imaging technology can address limitations by providing a method for improving in vitro studies used in drug discovery and development. They offer tissue analysis services for immuno-oncology research, which aims to understand how the immune system interacts with the tumor microenvironment and modulate the immune response to reduce tumor growth. They employ multiplex immunofluorescence to simultaneously interrogate multiple cell populations and use automated image processing algorithms to assess the variety and distribution of immune cells within and around tumor tissue. They also offer High Content Screening services to clients utilizing 3D cell models and traditional cell-based assays. They provide a wide range of validated in vitro screening services, rapid custom assay development, and end-to-end compound screening services.

3D Cell Culture Models

3D cell culture models are a method of growing cells that better replicates the complex characteristics of the in vivo microenvironment, such as diffusion gradients and receptor expression. Traditional 2D cell culture is limited in its ability to replicate these characteristics. The technique in which cells are cultured (2D vs. 3D) can substantially alter the drug’s effect on the cells. 3D cell culture models offer a more natural, tissue-mimicking method of cell growth for drug discovery applications.

Visikol’s expertise in 3D cell culture models and high content imaging technology allows for the assessment of multiple endpoints simultaneously at a cellular resolution. This provides richer datasets than traditional assays, enabling the interrogation and quantitation of cellular response of disease models to treatments, stimuli, or alterations in protein expression. The use of imaging-based endpoints allows for examination of the specific effect of compound treatments on specific sub-populations of cells, as well as providing access to more complex measurements than can be accomplished with traditional assay formats.

Visikol’s in vitro immuno-oncology models and high content imaging technology can provide a method for improving in vitro studies used in drug discovery and development. Their 3D cell culture models are more biologically relevant and allow for a proper assessment of immunotherapies designed to promote the immune cell response to tumor cells. Their high content imaging technology can help researchers and pharmaceutical companies maximize the potential of their immuno-oncology models by providing a method for assessing multiple endpoints simultaneously at a cellular resolution. By utilizing these technologies, researchers can obtain more accurate and reliable data for drug efficacy and safety testing, ultimately leading to the development of more effective cancer treatments.

If you’re interested in learning more, please reach out to a member of our team today!

Multiplex immunofluorescence microscopy is a cutting-edge technique that harnesses the power of multiple wavelengths of light and fluorescent markers to create intricate multi-spectral images, unlocking a wealth of possibilities for addressing diverse research inquiries. Visikol, from its inception, has been at the forefront of cell visualization, pioneering accessible tissue clearing reagents for multiplex immunofluorescent 3D microscopy.

Fluorescent Microscopy

In the realm of fluorescent microscopy, a dye-tagged antibody binds to the target antigen, enabling the visualization and quantitative assessment of specific points of interest. This target is rendered as a fluorescent pattern, emitting distinctive colors when exposed to a particular energy wavelength, releasing photons that can be captured and analyzed by the microscopy system.

Antibodies

The strength of this technique lies in its ability to yield highly contrasted, specific, and quantitative results. The quality of the data hinges on the antibodies’ specificity for their target antigens, as well as the brightness and contrast of the fluorescent labels. Historically, most labs have relied on single or double target detection due to its simplicity in planning and instrument requirements. However, this approach is limiting, particularly for complex research questions in areas like immune-oncology, where understanding the interactions between multiple cell types, such as T-cells, B-cells, and Natural Killer cells, is crucial.

Visualize up to 5 or More Targets

Multiplex immunofluorescence microscopy breaks free from these limitations, enabling the simultaneous visualization of up to five or more targets within cells or tissues. Given the intricate optimization involved, Visikol offers clients both pre-validated multiplex immunofluorescence panels and the flexibility to design and validate custom panels. Moreover, Visikol complements this with high-content imaging, image analysis, and comprehensive reporting. This integrated workflow empowers clients to swiftly transform their tissues into meaningful insights without the burden of developing resource-intensive in-house tissue processing, labeling, imaging, analysis, and reporting pipelines.

A Powerful Tool

In the realm of immuno-oncology, where targeted therapies are paramount, multiplex immunofluorescence emerges as a potent tool for identifying relevant biomarkers and characterizing alterations in their spatial distribution and activation states. Committed to advancing oncology drug discovery, Visikol offers pre-validated immune-oncology panels and stands ready to leverage these resources to address your specific research inquiries. If you’re interested in learning more reach out to a member of our team!

Immuno-oncology stands at the forefront of groundbreaking research, dedicated to developing therapies that harness the power of the immune system to combat cancer. The immune system, an intricate web of reactions and responses to cellular damage, infections, and diseases, including cancer, can be fine-tuned to target and treat cancer. This intricate system comprises two primary lines of defense: innate and adaptive immunity. Innate immunity encompasses the body’s surface barriers like the skin, as well as internal defenses such as fever and Natural Killer cells. On the other hand, adaptive immunity is developed through prior infections or vaccinations and involves the activation of T and B cells.

In the context of cancer and the immune system, a well-functioning cycle should unfold as follows:

-Cancer cells release antigens.
-Antigen-presenting cells capture these antigens.
-T cells are activated.
-T cells are recruited to the site of cancer.
-T cells infiltrate the cancerous tissue.
-T cells recognize and eliminate cancer cells.

Immuno-oncology

However, disruptions can occur in this cycle, causing cancer cells to evade the immune system’s surveillance. This evasion can result from factors like rapid cancer cell proliferation, which outpaces the immune system’s ability to eliminate them, or the creation of a hostile environment by cancer cells that hinders immune cell activity. This is where immuno-oncology steps in.

The primary objectives of immuno-oncology therapeutics, known as immunotherapies, are to either stimulate the immune system to identify and selectively attack cancer cells or recreate components of the immune system in the laboratory to enhance immune function. The choice of immunotherapy depends on the type of cancer being treated.

Cellular Immunotherapies and Antibody Therapies

Two prominent categories of immunotherapies under active research are cellular immunotherapies (including CAR-T therapy, TCR therapy, and TIL therapy) and antibody therapies. CAR-T therapy involves genetically modifying a patient’s T cells to equip them with specialized receptors for heightened effectiveness, predominantly successful against blood cancers. TCR therapy also utilizes a patient’s T cells, activating and arming them with new receptors to target specific cancer antigens. TIL therapy, most effective against melanoma, involves harvesting tumor-infiltrating lymphocytes from a tumor and reintroducing them into the patient’s system for treatment.

Antibody therapies employ targeted antibodies to disrupt cancer cell functions and alert the immune system to eliminate cancer cells. “Naked” monoclonal antibodies bind to cancer cell antigens, disrupting crucial pathways for cancer cell activity. Conjugated monoclonal antibodies are combined with chemotherapy drugs or radioactive particles for precise delivery directly to cancer cells.

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These examples merely scratch the surface of the exciting immuno-oncology research landscape. Visikol plays a crucial role in advancing immunotherapy development by offering a wide range of services and assays to support clients in their research endeavors. These services encompass Immune Cell Infiltration, Cell-Mediated Cytotoxicity/Effector Function, Antibody Penetration, and Immune Synapse Formation. Additionally, Visikol provides clients with diverse multiplexing techniques for histological slide analysis, including fluorescent multiplexing and imaging mass cytometry services. We encourage you to get in touch with our Visikol team to identify the most suitable assay and model for your specific research requirements.

Over the last decade there has been a boom of companies looking into immunotherapies for treating cancer and currently there are many different types of cancer immunotherapies that are being researched. Work is being conducted on immunomodulators (checkpoint inhibitors, cytokines), adoptive cell therapy (CAR-T, TCR, TIL), cancer vaccines, oncolytic virus therapy, and targeted antibodies. Each approach utilizes various components of the immune system as well as tackling different steps in the immune response cycle in order to treat cancer.

Immunomodulators, specifically checkpoint inhibitors, and adoptive cell therapies have seen the most recent advances. On July 24, 2020, the FDA approved a PD-L1 checkpoint inhibitor for the treatment of melanoma and on July 30, 2020 a CAR T cell immunotherapy was approved for the treatment of relapsed or refractory Mantle Cell Lymphoma. This is the first cell-based immunotherapy that has been approved for this cancer patient group. Immunomodulators are molecules or substances that have an effect on the pathways that regulate the immune system’s activities. Checkpoint inhibitors, as the name implies, blocks certain immune checkpoints. Adoptive cell therapies are an approach that uses the patient’s own immune cells to enhance the immune systems’ ability to eliminate cancer.

There has recently been a shift towards finding effective combinations of treatments such as pairing a checkpoint inhibitor (release the brakes) with a costimulatory receptor (step on the gas) to improve response rates. There has been a big push towards combining immunotherapies with traditional cancer therapies (i.e. chemotherapy). For example, on June 30, 2020 the FDA approved the combinational use of avelumab, a PD-1 inhibitor, with platinum-based chemotherapy as a maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. This is still a new approach that has many advantages but also disadvantages that researchers are striving to overcome.

In the last couple of years, the fields of nanotechnology and immunotherapy have merged. Nanoparticles can be used to encapsulate, carry, and deliver various chemotherapeutics or immunotherapeutics for increased stability and targeting. The effectiveness of these particles can be tuned and manipulated with surface modifications making it more adaptive. There is vast potential for the application of nanomedicine in immuno-oncology.

This is just scratching the surface of all the exciting research that is being conducted in the field of immuno-oncology. Visikol has a part to play in this process by offering various services and assays to help researchers further their work such as its Cell Mediated Cytotoxicity/Effector Function Assay, Antibody Penetration Assay, and Immune Cell Infiltration Assay. Additionally, Visikol most recently launched its multiplex slide imaging services which allow for the interrogation of 10+ markers simultaneously from a single tissue section

Contact us to work with our Visikol team to identify the best assay and model for your specific research needs.

Immuno-oncology is an exciting field of research that is focused on developing therapeutics the leverage the immune system to treat cancer. The immune system is a complex network of reactions and responses to cellular injury, infections, or diseases such as cancer and modulating these responses can be used to treat cancer. The immune system has two main immune defenses: innate and adaptive.  Innate immunity includes surface barriers such as the skin and internal defenses such as fever or Natural Killer cells. Adaptive immunity is developed from a previous infection or vaccination and includes T and B cells.

When it comes to the relationship between cancer and the immune system things can go awry. The general cycle should be as follows:

• The cancer cells release antigens.
• Antigen presenting cells capture antigens.
• T cells are activated.
• T cells are recruited to cancer site.
• T cells infiltrate the cancer.
• T cells recognize cancer cells.
• Cancer cells are killed.

However, cancer cells can overwhelm the immune system for various reasons interrupting this cycle. This could be caused by the cancer cells dividing faster than the immune cells can destroy them or the environment that the cancer cells have established is hostile for immune cells. This is where immuno-oncology comes into play.

The main goals of immuno-oncology therapeutics (immunotherapies) is to stimulate the immune system to be able to identify and selectively attack cancer cells, or mimic components of the immune system in the lab that can be used to restore/improve the immune system. There are many different types of immunotherapies and which would be the best choice for treatment will depend on the type of cancer.

Cellular immunotherapies (CAR-T therapy, TCR therapy, and TIL therapy) and antibody therapies are two types of immunotherapies that are being actively researched today. Chimeric Antigen Receptor T cell (CAR-T) therapy uses a patient’s own T cells that have been genetically altered to have special receptors on their surface to make them more effective. CAR-T therapies work well for blood cancers but are not as effective on solid tumors.  T cell Receptor (TCR) therapy also uses the patient’s own T cells. For this therapy T cells are activated and then equipped with new T cell receptors that will enable them to target specific cancer antigens. Tumor-infiltrating lymphocyte (TIL) therapy is most affective against melanoma. The principle behind this therapy is harvesting a tumor and isolating TILs from it. The tumor-infiltrating lymphocytes are then infused back into the patient for treatment.

Antibody therapies used targeted antibodies to disrupt cancer cell activity and alert the immune system to target and eliminate cancer cells. “Naked” monoclonal antibodies bind to antigens on cancer cells to disrupt important pathways for cancer cell activity. Conjugated monoclonal antibodies are combined with chemotherapy drugs or radioactive particles to provide a targeted delivery of these treatments directly to the cancer cells.

These are just a few examples of the exciting research that is being conducted in immuno-oncology. Visikol is contributing to the development of immunotherapies by offering a variety of services and assays to help clients further their research in this field. Possible cell-based assays include Immune Cell Infiltration, Cell Mediated Cytotoxicity/ Effector Function, Antibody Penetration, and Immune Synapse Formation. Additionally, Visikol provides its Clients with various multiplexing approaches for histological slide analysis such as fluorescent multiplexing or imaging mass cytometry services. Contact us to work with our Visikol team to identify the best assay and model for your specific research wants and needs.

Figure 1: T cell infiltration within tumor spheroid.  A) 10:1 effector to target ratio B) No T cells.