I-O Assays Introduction
The introduction of immuno-oncology therapies such as immune checkpoint inhibitors, adoptive cell therapies, and therapeutic cancer vaccines has significantly changed how cancer is treated. Still, it is difficult to turn promising laboratory results into real clinical progress. Because the tumor microenvironment is complex and involves many types of cells and interactions, researchers need strong and reliable in vivo models.
Applications of I-O Assays for In Vivo Study
| Application Area | Description |
|---|---|
| Candidate Selection and Validation | Validating the true therapeutic potential of leading drug candidates (e.g., bispecific antibodies, novel cytokine mimetics) by measuring tumor regression and overall survival in immunologically intact or humanized models. |
| Mechanism of Action (MOA) Elucidation | Providing granular data on immune cell infiltration, activation, and function within the TME to establish the agent's precise mechanism. This often involves determining if an agent primarily acts by increasing CD8+ T cell cytotoxicity or by altering the suppressive myeloid cell landscape. |
| Combination Therapy Strategy | Assessing synergistic effects of a new molecular entity when paired with established standards of care (e.g., anti-PD-1 or chemotherapy). In vivo assays reveal optimal dosing, scheduling, and sequencing required for maximal efficacy and minimal toxicity. |
| Biomarker Discovery and Validation | Identifying and validating predictive or pharmacodynamic biomarkers (e.g., changes in cytokine profiles, expression of co-stimulatory molecules) that correlate with therapeutic response, thereby streamlining patient stratification for future clinical trials. |
A Flexible Suite of Services at Creative Biolabs
GTOnco™ Cytokine Response Assay (In Vivo)
Cytokines are important in gene therapy-based I-O drugs development, specifically in host responses to immune responses and cancer. GTOnco™ provides various cytokine detection by ELISA or ELISpot assays, such as chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors.
GTOnco™ Lymphocyte Activation & Proliferation Assay
Cell activation and proliferation are expected to be earlier indicators of the response to immune stimuli, and the related assays have been shown to be useful for monitoring T-cell immune status. At Creative Biolabs, GTOnco™ is able to provide faster, easier-to-use methods for measuring T-cell activation and proliferation in response to a variety of stimuli.
GTOnco™ T Cell Persistence & Trafficking Assay
T cells persistence is likely to promote long-term anti-tumor effects in I-O drug therapy, such as adoptive T cell transfer. In addition, active T cells reprogram the trafficking properties of T cells and allow them to effectively and specifically settle to extra lymphoid organs. GTOnco™ platform has established effective in vivo methods to study the T cell persistence and provides the observations of organ-specific homing of T cells.
GTOnco™ Immune Cell-Mediated Tumor Regression Assay
Creative Biolabs is capable of conducting many tests to evaluate the immune cell-mediated tumor regression efficacy in I-O drugs therapy, such as in vivo imaging and flow cytometry. By utilizing appropriate animal models, GTOnco™ platform provides the high-quality therapeutic efficacy test services to help our customers and expedite their IND application.
GTOnco™ TCR-pMHC Dissociation Kinetics
The dissociation kinetics of TCR binding to peptide-major histocompatibility molecules (pMHC) is a robust and stable biomarker of CD8+ T cell potency. The TCR-pMHC dissociation rates accurately predict the cytokine production, cell proliferation, and in vivo antitumor potency of naturally occurring antigen-specific CD8+ T cells.
GTOnco™ Redirected T Cell Cytotoxicity Assay
Gene therapy-based immuno-oncology (I-O) drugs, which are designed to recruit and redirect T cells to specifically target and attack tumor cells, hold tremendous potential for revolutionizing the treatment of various malignancies. These innovative therapies harness the body’s own immune system, empowering it to recognize and combat cancer more effectively.
Models of Immuno-Oncology Detection for In Vivo Studies
The GTOnco™ platform offers a comprehensive portfolio of validated in vivo models, each with unique advantages.
Homologous Models
These models are the backbone of immuno-oncology research. We offer a variety of well-defined mouse tumor cell lines (e.g., MC38, B16-F10, CT26, 4T1) that have been implanted into immunocompetent hosts. These models possess a complete mouse immune system, making them ideal for studying the mechanisms of action of immunomodulators targeting innate immune pathways.
Genetically Engineered Mouse Models (GEMMs)
For example, the Kras^LSL-G12D/+; p53^fl/fl (KP) lung adenocarcinoma model, which spontaneously forms heterogeneous tumors in an immunocompetent background. This autologous nature allows for a more accurate mimicking of human tumorigenesis, including the formation of an immune-edited tumor microenvironment (TME), thus providing rigorous validation of therapeutic efficacy.
Humanized Mouse Models
For drugs targeting human-specific antigens (e.g., human CD3, CD19, PD-L1), we employ humanized models. By transplanting human immune cells into NOG or NSG mice, we construct chimeric human immune systems. This is crucial for evaluating therapies that do not cross-react with murine counterparts.
Our Collaboration Process
Our collaboration begins well before the first dosing, ensuring the assay methods perfectly align with your translational goals.
Initial Consultation
A dedicated GTOnco™ scientist will discuss the mechanism of action (MOA) of your chosen molecule, its species specificity, and preclinical research objectives with you.
Study Design
We will work with you to design a robust and statistically significant protocol, including model selection, dosing regimen, and comprehensive endpoint assays.
Experiment Execution
Studies are conducted by trained technicians under rigorous QA/QC protocols, with continuous monitoring of animal health and tumor size.
Sample Analysis
Ex vivo samples are processed immediately to ensure cells maintain optimal viability and integrity before in-depth phenotypic analysis.
Reporting
You will receive a final comprehensive report containing statistical analysis, detailed graphs, and a definitive scientific interpretation.
GTOnco™ Platform Advantages and Highlights
Unparalleled Model Portfolio
We possess one of the industry's largest and most validated libraries of homologous, genetically engineered mouse models (GEMMs) and humanized models, allowing for customized model selection to address your specific biological questions.
Integrated Multi-omics Endpoint Analysis
We transcend the limitations of tumor volume. Our standard services include high-parameter flow cytometry (up to 30 colors), cytokine profiling, and immunohistochemistry (IHC).
Rational Combination Therapy Design
Our team of PhD-level scientists will collaborate with you to design rational combination therapy strategies based on the latest understanding of immune signaling pathways and drug resistance mechanisms.
Proprietary Data Analysis Platform
We provide clients with access to a bioinformatics platform containing historical control data and advanced analytical tools, enabling benchmarking of your results against a vast internal dataset, significantly enhancing your data interpretation capabilities.
Customer Review
Dr. Alex Chen
VP of Preclinical Development
“We urgently needed to test the in vivo efficacy of a novel T-cell connective in a highly specific homology model, so we contacted Creative Biolabs. The GTOnco™ team performed exceptionally well. Their ability to custom-build models allowed us to rapidly inoculate and validate the required models, while their fast-turnaround FACS analysis provided us with critical data on T-cell activation within three weeks. This speed significantly accelerated the studies required for our IND submission.”
Dr. Evelyn Reed
CSO
“Our initial in vivo studies using standard monitoring methods were not well-defined. Partnering with Creative Biolabs and utilizing their full suite of GTOnco™ assays, particularly their 30-color CyTOF assay, revolutionized our results. We not only observed tumor regression but also precisely located the exhausted T-cell subsets that our antibody successfully activated. This deep mechanistic insight was crucial for our regulatory filings and subsequent funding.”
Frequently Asked Questions
Model selection is custom-designed. For novel ICIs, we typically choose established homologous models (e.g., MC38, B16-F10) that have demonstrated known ICI sensitivity. If the drug is species-specific (e.g., targeting an epitope present only in humans), a humanized mouse model must be used. We guide model selection based on the drug's target and mechanism of action (MOA).
Standard homologous efficacy studies (from tumor inoculation to final reporting) typically take 6–10 weeks, depending on tumor growth rate and observation period. Custom-designed humanized models typically take longer (12–16 weeks) due to the need for transplantation.
Our standard reports include raw data files (FCS), detailed gating strategies, and expert-level analytical plots. For high-dimensional data, we offer unsupervised clustering and visualization (e.g., t-SNE or UMAP) to highlight statistically significant phenotypic changes associated with treatment efficacy.
Homology models are ideal for studying the mechanism of action of drugs targeting conserved mouse pathways (e.g., mouse PD-1) within the intact immune system. Humanized models are crucial for drugs targeting human proteins (e.g., human CD3 bispecific antibodies) or for assessing human-specific immune responses and toxicity.
Absolutely. Our greatest value lies in our scientific collaboration. We will work with you to review existing data, propose phased experimental strategies, and select the most appropriate models and endpoints to minimize your project risk and maximize information output.
Connect with Us Anytime!
Creative Biolabs is able to help you design the best assays for customized in vivo studies to support your gene therapy-based I-O drugs discovery. All our experiments are performed by well-trained technicians in a GLP-compliant and IACUC-regulated facility. Please feel free to contact us by E-mail for a quote and further discussion with our scientists.
Tell us about your project, and our experts will get back to you with a customized quote and proposal.
