In Vivo Contract Research Services (Xenograft, PDX)
Altogen Labs, a pre-clinical contract research organization (CRO), provides PDX models, patient chemosensitivity xenograft testing (PCX), as well as over 90 standard CDX validated in vivo xenograft models for efficacy studies on drugs, oncologic treatments and laboratory research including pharmacokinetic and toxicology studies (ADME, PK/PD, IC50, LD50, and many more). These models can be used for drug discovery, cancer studies, and treatment improvement, as well as numerous oncology research applications. Xenograft immunocompromised mice-based models provide adequate test models for different types of human cancer, diabetes, wound healing, and other conditions.
The patient-derived human tumor xenografts (PDX) are explants directly injected to the xenograft model and not propagated in vitro. Altogen Labs provides validated histotypes for both preclinical and clinical research applications, however there are certain advantages and disadvantages of PDX xenograft models:
The mouse xenograft models are widely used for cancer therapy research due to the following advantages:
- They can be used for personalized therapy research, and the results are obtained relatively fast
- The human tumor stroma can be included in the xenograft
- The researcher studies human tumor response in vivo (in vitro results are known to translate poorly)
- The same tumor can be used for testing different drugs or concentrations
- Orthotopic xenografts can be obtained and studied
- “Humanized” mice can be used
These observations make the mouse xenograft models a very useful tool, which can be manipulated to simulate the original tumor response, however the techniques also have some disadvantages:
- Although very useful, orthotopic xenografts are known to be very expensive (2-3 times more expensive compared to CDX xenograft models)
- The SCID or athymic nude mice (immunocompromised) are not capable of exhibiting an immune response
Altogen Labs provides PDX models and services for the establishment and expansion of Patient Derived tumor Xenografts.
Basic PDX service includes:
- Prepare and implant patient-derived-tumor samples in female athymic nude mice
- Grow and monitor tumors to maximum size allowed in protocol (1000-1500 mm3); this is termed the F0 tumor generation
- Excise F0 tumors and process for storage and implantation for expansion to generate F1 tumors
- Excise F1 tumors and process for storage and implantation for expansion to generate established F2 and subsequent tumor generations (F3…Fn)
- Implantation of established tumor generations will be of use for treatment studies as outlined in the basic xenograft study design
Possible murine models for xenotransplantation include:
- 6- to 7-week-old female BALB/c athymic (nude) mice
- 9-11 week old NOD/SCID immunocompromised mice
- the mouse line of the client’s choice (other mouse lines are described here)
Xenografting is typically accomplished by subcutaneous (s.c.) injection of one million cells per animal from the selected tumor cell line. Xenotransplantation in other areas may be possible upon consultation with Altogen Labs. We offer assistance in choosing the best model suitable for the client’s goals. In addition, there are tools available to search for specific models.
Some study objectives may be to identify therapies that target specific carcinogenesis pathways that are dysregulated in tumor cells. In this case, tumor cell lines with known genetic mutations will be used to demonstrate pathway-dependent therapy. Altogen Labs will aid the client in choosing the most useful cell line(s) from the myriad of choices.
Clients choose a tumorigenic cell line of interest, an animal model, and select the desired number and size of experimental groups. Following acclimation to the vivarium environment, the chosen mice are sorted according to body mass. The selected cancer cell lines are prepared in Matrigel and grafted subcutaneously into the flank area (or elsewhere as per the client’s instruction). The animals are examined daily for tumor appearance and clinical signs. When tumors are established, animals are sorted based on tumor volume.
Cell Engraftment Options
Alternative cell engraftment sites will be used if required. Common alternative sites include:
- Injection into the mammary fat pad (breast cancer models)
- Intraperitoneal injection (ovarian cancer models)
- Orthotopic transplantation in the prostate
- Tail vein injection and left ventricular injection for metastasis studies
The dosing of the experimental compound of interest is initiated, for a staged study, when the mean tumor size reaches a specified volume (typically 50-100 mm3). In an unstaged study, the dosing of the compound of interest is initiated immediately after xenografting. Mice are dosed once or twice a day for 28 days (or other desired study duration) via the chosen route of administration. Tumor volume (mm3) is calculated via the “(W x W x L) / 2” formula, where W is tumor width and L is tumor length.
Treatment Options
Most treatment options required by the client can be accommodated. We also offer services to quickly determine the optimal route of administration and treatment schedule for your test compound.
Options for administration of the compound of interest include:
- Dosing route: intratumoral, oral (gavage or via dietary admixture), topical, intramuscular, subcutaneous, intranasal, intravenous, intratracheal, via continuous infusion, implantation of slow release pellets, implantation of osmotic pumps or intraperitoneal
- Dosing frequency
- Duration of dose administration
- We also offer the possibility of a positive control group employing cyclophosphamide, at a dosage of 25-40 mg/kg administered by intramuscular injection to the control group daily for the study duration
All studies performed by Altogen Labs include daily cage-side observations by experienced scientists. Whole body weight and tumor volumes are measured every two days.
Animal Disease Model Optimization
We strongly support the use of the most suitable animal models for scientific inquiry. The information gained from this investigation is used to create life-saving drugs and regimens for various diseases and conditions. Our xenograft CRO facility has the capacity to hold up to 1000 mice at a time. These mice are routinely examined for tumor growth delay (TGD, latency), tumor growth inhibition (TGI), toxicity and rates of survival. Previously, our xenograft research has been used to determine lead compounds, modify dose schedules and ascertain combination strategies. Our team also has the necessary skills to assist you in understanding the molecular mechanics of drug action using our in vivo models.
Experimental Methods
Our in vivo xenograft CRO services include the whole gamut of research assistance including the following:
- Biospecimen collection
- Caliper measurements
- Mouse model induction
- Xenograft and orthotopic transplantation
Our repertoire also includes the following support services:
- Blood and urine glucose
- Clinical chemistry
- Histological services
- Lipid distribution
- Metabolic assays
- Access to specialized imaging: MRI, micro-CT, PET
Alternative Protocols
Our in vivo xenograft CRO services are entirely customizable. Our well-equipped laboratory and expert scientific staff can help you by:
- Providing in-house or accommodating customer-provided cell lines
- Providing staged or un-staged testing facility
- Assigning mice to groups at random or classifying them by weight, tumor size or any other parameters of your choice
- Administering test compounds by a number of different methods
- Providing snap-freeze and LN2 storage for collected tumors
- Fixing collected tumors for histology or any other specific assays
- We also have in-house facilities to analyze toxicology clinical parameters, blood chemistry, cell count, clinical pathology, etc
Results and Analysis
No matter how long your study or how intricate its requirements are, you can depend on us for a complete analysis of the data. We will present you with the results and summary along with all of the following and other information at your request:
- Tumor cell kill rate
- Tumor growth inhibition (TGI)
- Tumor growth delay (TGD)
- Increased life span (ILS)
- Estimated tumor volume
- Survival time to specified tumor volume
- Tumor doubling time
Collaborative Research Opportunities
At Altogen Labs, we understand the importance of collaboration in advancing scientific discovery. We offer tailored research partnerships designed to meet the unique needs of academic institutions, biotech firms, and pharmaceutical companies. Our collaborative approach ensures that every research project benefits from shared expertise, rigorous methodology, and innovative solutions. We welcome opportunities to work closely with clients to co-author research publications, participate in grant applications, or engage in strategic partnerships to accelerate therapeutic development.
Data Integrity and Quality Assurance
We prioritize the highest standards of data integrity and quality assurance throughout our research processes. Altogen Labs is committed to adhering to GLP (Good Laboratory Practice) guidelines and employing stringent quality control measures to ensure reliable and reproducible results. All procedures are meticulously documented, and our team of experienced scientists conducts regular audits and reviews to maintain accuracy and compliance. Our comprehensive reporting includes raw data, statistical analysis, and detailed interpretations to support robust scientific conclusions.
Advanced Imaging and Molecular Analysis
Beyond traditional endpoints, Altogen Labs provides advanced imaging and molecular analysis services to further elucidate the mechanisms of drug action and tumor biology. We leverage cutting-edge imaging technologies, including MRI, micro-CT, and PET, to capture high-resolution images of tumor progression and therapeutic response. Additionally, our molecular analysis capabilities include gene expression profiling, protein quantification, and biomarker identification, offering clients a deeper understanding of the underlying biology of their models.
Customization and Flexibility
We understand that each research project comes with its own set of challenges and goals. To address these, Altogen Labs offers unparalleled flexibility in study design and execution. Our team works closely with clients to customize experimental protocols, select the most relevant tumor models, and adjust treatment regimens as needed. Whether your project requires non-standard cell lines, unique administration routes, or bespoke data analysis methods, we are equipped to accommodate your specifications and provide insightful recommendations.
Post-Study Support and Data Interpretation
Our commitment to excellence does not end with the completion of your study. We provide comprehensive post-study support, including in-depth data interpretation, manuscript preparation assistance, and follow-up consultations. Our experts are available to discuss findings, suggest next steps, and explore potential avenues for further research. We aim to empower our clients with actionable insights that can drive their research forward and inform future therapeutic strategies.
Ethical and Humane Animal Research
Altogen Labs is dedicated to conducting ethical and humane animal research. We comply with all relevant ethical guidelines and institutional animal care and use committee (IACUC) regulations to ensure the welfare of our animal models. Our facility is staffed by trained veterinarians and animal care specialists who oversee daily animal health and well-being. We continuously seek to refine our techniques and adopt the 3Rs principle (Replacement, Reduction, and Refinement) to minimize animal use and ensure ethical research practices.
Request a quote for xenograft study at https://altogenlabs.com/request-quote/