Oncology
Recapitulation of human immune-tumour microenvironment in HiMice model serves as the most advanced and promising platform for immunotherapeutic drug efficacy and safety assessment. At Invivocue, we establish the tumor models using Patient-derived Xenograft (PDX) or Cell Line- derived Xenograft (CDX). It has been scientifically proven that human tumor growth in HiMice evolves significantly in the presence of human immune system and provides notable expression of immune checkpoints compared to conventional nude, immunodeficient and syngeneic mouse model. Importantly, the research outcomes provide a better representation of the clinical conditions.
Patient-Derived Xenograft (PDX)
Our Patient-derived Xenograft (PDX) models are generated by implanting patient tumor tissue such as patient-derived primary cells or organoids directly into immunodeficient mice and humanized mice via subcutaneous or orthotopic transplantation. This allows the tumor to grow in a more natural environment and to mimic clinical disease pathogenesis. PDX models are widely used in pre-clinical cancer research for drug discovery and personalized medicine. They offer a valuable tool for studying tumor biology, evaluating drug efficacy, and predicting patient response to therapies.
Figure: Establishment of PDX using Patient tumor biopsy or Patient-derived Organoid (PDO) in HiMice.
Service: In vitro efficacy screening, PDX in Immunodeficient mice, HiMice, Myeloid enhanced HiMice, NK cell enhanced HiMice or PBMC Mice.
Deliverables:
Body weight
Tumor Growth Kinetics
Blood and Organs Immune Profiling
Tumor infiltration Lymphocyte Profiling
Cytokine Profiling
Tumor Marker analysis (IHC/IF/qPCR/sequencing)
Histopathology analysis
List of PDX
PDX model has a unique biomarker characteristics, which means you can choose the best PDX model based on your research needs. In addition, we are also open for collaboration to develop new PDX models for specific research objectives and biobanking purposes.
At Invivocue, we obtained patient tumor via proper patient informed consent and strictly adhere to applicable national guidelines in usage of patient-derived tissues for cancer research.
List of PDX
Breast Carcinoma, Stage IV
Lung Adenocarcinoma, Stage IV
Ovarian Adenocarcinoma, Stage IV
Colorectal Adenocarcinoma, Stage IV
Pancreatic Adenocarcinoma, Stage IV
Data
Our humanized mouse models provide a valuable platform for testing the efficacy, safety and pharmacokinetics of various cancer therapies including antibody-dependent cell-mediated cytotoxicity (ADCC), immune checkpoint inhibitors, CAR-T, CAR-NK, cytokine inhibitors.
A
Humanized mice supports growth of PDX via subcutaneous, intravenous or orthotopic transplantation of human primary cancer cells, Patient-derived Organoid (PDO) and human tumor tissues.
B
Images of Lung (left) and breast (right) PDX implanted and grown subcutaneously on immune deficient and humanized mice. Positive pan-cytokeratin (Pan-CK) immunohistochemical stain confirms tumorigenesis of PDX.
C
Patient-derived xenograft is widely accepted as a “gold standard” for human-specific immuno-oncology drug evaluation. Data below demonstrates that PDX in HiMice respond positively to clinical anti-cancer drug therapies such as Pembrolizumab (PD-1 inhibitor), Bevacizumab (anti-VEGF antibody) and combinational therapy.
Cell Line-Derived Xenograft (CDX)
CDX models were generated by implantation of commercially available tumor cell lines into immunodeficient mice or humanized mice for in vivo efficacy evaluation of various cancer therapies, including cell therapy, gene therapy and immuno-oncology drugs.
CDX testing platforms are known to be relatively simpler, consistent and can be set up quickly to obtain valuable efficacy and bioavailability data during the early-stage development process to shortlist drug candidates and/or refine treatment regimens. Importantly, cell lines for CDX models are usually commercially available, their tumor growth profile and biomarkers are well characterized as compared to PDX.
Animal Model: Immunodeficient mice or humanized mice models with intact human immune system
Route of administration of cells: subcutaneous, orthotopic, Intravenous
Type of CDX available: Lung, breast, colorectal, ovarian, prostate, lymphoma, glioblastoma, myeloma, liver and renal
Case Study
Gastric tumors with higher epigenetic promoter alterations (APBhigh) exhibited decreased levels of CD8+ T-cell infiltration and is associated with resistance to immune checkpoint inhibition in patients
Figure: Interaction between alternate promoter use and human immune system.
Humanized and immunodeficient NSG mice were engrafted with two APBhigh and two APBlow gastric cancer cell lines and observed for 1 month. (Left panel) APBhigh tumors have faster growth in humanized mice compared with NSG mice, while in APBlow tumors, humanized mice have slower growth. Cyan lines are humanized mice; magenta lines are NSG mice. (Right panel) CD3 and CD8 immunohistochemical tumor staining shows increased lymphocyte infiltration in APBlow (black arrows) and no infiltration in APBhigh. Scale bar: 50 μm.
Source: Raghav et al. 2021. Gut. doi: 10.1136/gutjnl-2021-324420.
Syngeneic Tumor Models
A syngeneic mouse model is created by implanting immortalized mouse cancer cell lines into wild-type mouse strains such as Balb/c or C57BL/6. Mouse tumour cells grow in an immunocompetent environment provides an effective in vivo platform to study the efficacy of cancer therapies in the presence of a functional immune system.
Pros
Easy to Use – Well-established models with high tumor engraftment rate
Complete immune system
Cost-effective - Short-efficacy study
Cons
Tumor is usually aggressive and leads to short study period
Limited choice for murine cancer cell lines
Mouse Immune system may not translate to human immune system
Animal Model: Balb/c or C57BL/6
Route of administration of cells: subcutaneous, orthotopic, Intravenous
Murine cancer cell lines: Renal, Lung, Breast, Colorectal, Lymphoma, Melanoma
Model development: Tumor cells were first subcutaneously injected into shaved right flank of adult BALB/c mouse. Upon reaching the desired tumor size (e.g 50-100mm3), the mice will be administered with test article (s) for 10-28 days, depending on cancer type. In parallel, tumor bearing mice injected with vehicle control are included as negative controls. The tumor length and width will be monitored 2-3x weekly by vernier caliper (manual) or bioluminescent imaging system (Imaging).
Given the complexity of human disease, in-depth knowledge of each model is key to success in pre-clinical studies. Invivocue offers tailor-made study designs to suit your research needs.