GTOnco™ I-O Assays Service for In Vitro Study
For gene therapy-based I-O drugs discovery, Creative Biolabs offers a variety of prove-of-concept in vitro assays to test the pharmacological activity. Generally, I-O drugs in gene therapy are able to activate the body's immune system and stimulate the immune cells to target and attack the tumor. On the basis of mechanisms underlining I-O drugs in gene therapy and current studies, we have leveraged the cutting-edge technologies to build a groundbreaking platform for in vitro testing of I-O agents, especially with the immune system activation assays and immune cell-mediated anti-tumor effect study. Multiple assays have been developed and numerous assays kits are also available at GTOnco™ platform.
Introduction of In Vitro I-O assays
The rapid advancement of the field of immuno-oncology (I-O) has revolutionized our understanding of cancer biology and therapeutic development, highlighting the critical role of the immune system in tumor control and clearance. In vitro I-O assays are indispensable tools in this field, providing controlled and reproducible systems for studying the complex interactions between cancer cells and the immune system, free from the confounding variables of the in vivo environment. These assays enable researchers to precisely and scalably dissect molecular mechanisms, identify new therapeutic targets, and evaluate the efficacy of emerging immunomodulatory agents.
Immune System Activation Study
Gene therapy-based I-O drugs are able to boost the immune response or prevent its attenuation. To this end, several methods have been developed, such as the use of immune checkpoint inhibitors (ICI) to reverse the inhibition of adaptive immunity, immuno-modulatory cytokines to switch on adaptive immunity, adoptive cell transfer (ACT) and genetically engineered oncolytic viruses (OVs) and cancer vaccines to activate the immune system. The activation of the immune system is usually accompanied by T cell proliferation and activation, and the release of cytokines, such as IL-1, TNF-α, and IL-6, etc.
Figure 1. T-cell activation mechanisms.1
Immune Cell-mediated Anti-tumor Effect Study
Contrary to traditional therapies that directly target malignant cells, I-O drugs in gene therapy act by stimulating the body's immune system to target and attack the tumor. Enhancement of effector cells' cancer-killing functions can be achieved by appropriately igniting the immune system with I-O drugs. Immune cells that are thought to contribute directly or indirectly to the demise of tumor cells include the activated natural killer (NK) cells, the subsets of cytotoxic (Tc) and helper (Th) T lymphocytes, macrophages, granulocytes, B cells and dendritic cells (DC). These complex interactions of immune cells should result in tumor cell death.
Figure 2. Immune cell-mediated anti-tumor effect.1
Key Immune-Oncology Processes Modeled by GTOnco™ I-O Assays
| Biological Process | Assay Type | Measurable Parameters |
|---|---|---|
| Immune Cell Cytotoxicity | NK cell killing assay | Target cell death, caspase activation, granzyme B release |
| Immune Cell Proliferation | Cell proliferation assay | CFSE dilution, Ki67 expression, ATP quantification |
| Cytokine Production | Cytokine release assay | Multiplex cytokine profiling (IFN-γ, TNF-α, IL-2, IL-6, etc.) |
| Immune Cell Phenotyping | Flow cytometry panels | Surface marker expression, activation/inhibition receptors |
| Antigen-Specific Responses | ELISPOT/FluoroSPOT | Cytokine-secreting cells, tumor-reactive T cells |
I-O Assay Types for In Vitro Study
Immune Cytotoxicity Assays
Quantify the ability of immune effector cells to recognize and kill cancer cells, a fundamental endpoint for successful anti-tumor immunity.
Immune Cell Activation and Proliferation Assays
Measure the initial immune recognition events and subsequent clonal expansion that underlie adaptive anti-tumor responses.
Cytokine and Chemokine Profiling Assays
Characterize the soluble mediator milieu that influences the quality, intensity, and duration of immune responses.
Immune Checkpoint and Co-signaling Molecule Assays
Evaluate regulatory signals that fine-tune immune responses through receptor-ligand interactions.
Antigen-Specific T Cell Response Assays
Detect and characterize T cells that recognize specific tumor antigens, which is crucial for vaccine development and adoptive cell therapy.
Immune Cell Migration and Invasion Assays
Study the ability of immune cells to signal to tumors, a critical step in effective anti-tumor immunity.
Core Services at Creative Biolabs
The GTOnco™ I-O assay platform distinguishes itself through several fundamental advantages, offering tangible benefits to cancer researchers and therapeutic developers. These classical methods are specifically designed for I-O applications, enabling exceptional sensitivity in detecting immune-mediated reversion of transformed phenotypes — a critical capability for assessing immune-mediated tumor control.
- Immune System Activation Service
As a world-leading expert in gene therapy-based I-O drug discovery field, we can provide both well-established and custom designed assays that are available at GTOnco™ platform to study the I-O drugs mediated immune system responses, specifically cytokine release and activation of various immune cells.
- Immune Cell-Mediated Cancer Cell Killing Strategies
At GTOnco™ platform, we are experienced in a variety of immune cell-mediated cancer cell killing strategies including NK or effector T cells. We also provide a range of in vitro assays service to study the regulation of the tumor microenvironment and immune cell-mediated anti-tumor immune response profiling to support your gene therapy-based I-O drug discovery, which allow you to move with confidence to the next phase of drug development.
Comparative Advantages of GTOnco™ Platform Features
| Feature | Conventional Assays | GTOnco™ Platform | Research Impact |
|---|---|---|---|
| Parameter Depth | Single or limited endpoints | Multiplexed, high-content readouts | Comprehensive immune profiling from limited samples |
| Physiological Relevance | Simple 2D monocultures | Advanced 3D co-culture TME models | Enhanced in vivo predictive value |
| Translational Utility | Species-specific assays | Cross-species validated platforms | Direct preclinical-to-clinical translation |
| Functional Assessment | Isolated functional readouts | Integrated functional systems | More clinically relevant activity data |
| Quality Standards | Research-grade validation | Rigorous, statistically-powered validation | Decision-ready data for therapeutic development |
Reasons to Choose Creative Biolabs
Choosing the right partner for your immuno-oncology research is crucial and can significantly impact the success and progress of your therapeutic development project. Creative Biolabs stands out through its commitment to scientific excellence, innovative technology, and customer-centric collaboration, providing unparalleled value throughout the R&D process.
Immuno-Oncology Assay Development Expertise
Our team of PhD-level scientists translates this expertise into sophisticated experimental designs that capture biologically relevant endpoints while mitigating common pitfalls in immune cell assays.
Fully Integrated Service Portfolio
From initial immune cell isolation to advanced functional characterization, we offer comprehensive services without the need to coordinate with multiple vendors.
Proprietary Technology Platform
In addition to implementing standard protocols, we systematically enhance key assay parameters through proprietary modifications, significantly improving data quality and biological relevance.
Streamlined Workflow and Project Management
Each client project is assigned a PhD-level project manager who serves as your single point of contact and scientific advocate throughout the collaboration.
Customer Review
"We used the phagocytosis assay to screen small molecule inhibitors of the tumor-macrophage interaction pathway. The real-time imaging capability provided mechanistic insights that we could not obtain using simple endpoint analysis. The prompt communication from the Creative Biolabs team was exemplary."
— Professor Kenji Tanaka, Principal Investigator
"Their ability to handle complex gene therapy vectors and primary human cells is unparalleled. The GTOnco™ cytokine response assay, utilizing their multiplexed platform, not only demonstrated robust efficacy but also flagged potentially safety-related cytokine release signatures early, allowing us to proactively modify our construct."
— Dr. Lena Petrova, Head of Preclinical Development
Frequently Asked Questions
Q: What controls are included in the GTOnco™ assays to ensure interpretability of the results?
A: All GTOnco™ assays include appropriate controls, such as reference standards, background measurements, and quality control samples that are processed identically to the experimental samples. For cell-based assays, we typically include positive and negative stimulation conditions, effector cell-only controls, and target cell-only controls to allow for specific interpretation of observed effects. Specific controls vary by assay type and are detailed in our respective assay specifications.
Q: How does your platform address inter-donor variability in primary immune cell assays?
A: We mitigate donor variability through multiple strategies: (1) Where appropriate, we use commercially available, identified donors with documented immune responses; (2) For studies requiring multiple donors, we stratify enrollment based on relevant characteristics; and (3) Our statistical methods account for donor effects through appropriate experimental designs and mixed-effects models. For key applications, we can discuss the advantages of using autologous systems with matched immune and tumor cells.
Q: Can the GTOnco™ assays be adapted to specific tumor microenvironment conditions?
A: Yes. We frequently customize assays to mimic tumor microenvironmental conditions, such as hypoxia, nutrient stress, or a specific cytokine milieu. Our advanced co-culture systems can include multiple cell types (e.g., cancer-associated fibroblasts, endothelial cells) to better mimic the complexity of the actual tumor microenvironment.
Q: How do you ensure the quality of primary immune cells used in the assays?
A: We enforce stringent QC measures, including a minimum post-thaw viability of >90, functional validation with standard mitogens (PMA/Ionomycin or anti-CD3/CD28), and phenotypic analysis via flow cytometry to confirm cell population integrity (e.g., percentages of CD4+, CD8+, NK cells).
We're Here to Help—Contact Us!
The GTOnco™ I-O Assays platform represents a strategic advancement in preclinical modeling. By coupling highly complex, physiologically relevant 3D co-culture models with high-content, high-throughput analysis, it offers an unprecedented level of predictive capability for novel I-O agents. Scientists at Creative Biolabs are able to help you design the best-fit assays for customized in vitro studies. We will work closely with our clients to design the optimal protocol for the gene therapy-based immune-oncology drugs development. Contact us for free expert advice to support all of your I-O research needs.
Reference
- Marshall, H. and Djamgoz, M. (2018). Immuno-Oncology: Emerging Targets and Combination Therapies. Frontiers in Oncology, 2018, 8: 315. https://doi.org/10.3389/fonc.2018.00315 (Distributed under Open Access license CC BY 4.0, without modification.)
