Services • In vivo
Important step in preclinical drug development is demonstrating the antitumor activity of a novel agent in animal models, as well as defining the dosage and schedule that is both efficient and non-toxic.
KINETO Lab proposes in vivo preclinical models which can be used per se or associated with imaging modalities to permit the evaluation new therapeutics efficacy in development phase.
MOUSE STRAINS SUITABLE FOR ANIMAL STUDIES
Experimental animal models are a crucial tool in the field of cancer research for testing new therapeutic approaches and validating their in vitro achievements. KINETO Lab provides you opportunity to choose the most adequate tumor bearing mice model as of high importance for successful evaluation of your therapeutic activity which can lead to candidate for clinical investigation.
We have all necessary approvals for animal experimentation which allow us to implant those models in immunodeficient (SCID, NOD-SCID and NSG) and immunocompetent (C57BL/6, BALB/c, BDF1) mice. If your model requires another strain of mice, or if you have custom enquire, we can solve husbandry and experiments with your customize choice.
With our specific knowledge and experience which strain and sex is the most suitable for a particular tumor model, your research or development project will be done efficiently.
We possess a collection of 70 human cell lines and 10 murine cell lines cell lines, as well as patient-derived tumor samples to test your compounds in vivo.
For our models, we have established patterns for number of cells or size of tumors to be inoculated or transplanted for a certain site of establishment, in order to develop models with suitable duration for quality antitumor or antimetastatic evaluation of therapeutic.
We have different tumor models:
KINETO Lab has wide range of xenograft models established from cell lines derived from human tumoral primary cells, which have been tested for their capacity to grow in immunodeficient mice, where you can test your compounds against human targets.
The allograft tumor models, growing of murine tumors in immunocompetent mice, provide therapeutics investigation in presence of native immune system, and represent suitable platform for testing agents from immuno-oncology field.
PDTX models are the most advantages because they provide more complex and more heterogenetic properties mimicking on the best way tumor microenvironment.
KINETO Lab has also developed and validated patient-derived tumor xenograft (PDTX) models with unique characteristics allowing to study drug efficacy in vivo in clinically relevant models, reflecting tumor heterogeneity, and microenvironment of the patients.
Patient Derived Tumor Xenografts (PDTX)
Patient derived tumor xenografts (PDTX) are created when cancerous tissue from a patient’s tumor is implanted directly into an immunodeficient mouse. Tumor models including xenografts in mice were used previously mostly in the development of new anticancer drugs. Nowadays, xenografts from direct patient-derived tumor tissues in immunodeficient mice yield better models than experimental tumors originating from cell cultures. The new method allows researchers to observe heterogeneous tumor cells with their surrounding tissue elements and matrices representing the clinical situation in patients much better. The cells in PDTX tumors are alive and functionally active through several generations after serial transplantation. Using these models we may investigate tumor response to different therapies, the selection of resistant cell populations and the formation of metastasis predicting the outcomes in the personalized therapy.
IN VIVO TOXICOLOGY AND PHARMACOKINETIC STUDIES
Tumor-free mice are used to test compound safety and pharmacokinetics.
- Acute toxicology studies of a compound on healthy mice: 1 administration. Different doses.
- Chronic toxicology studies of therapeutic: multiple administrations with dose which will be used in tumor bearing mice.
The analysis of the toxicity of new compounds on healthy mice is essential for the drug development process. KINETO Lab determines toxicity profile of therapeutic agents, by evaluation of the health status of mice with the following parameters: animal body weight, behavior, fur status, breathing, prostration, appearance, fatty, eating, moving, activity, coordination, which changes are the critical characteristics in toxicity testing as animals should be protected from stress and pain.
In addition, determination of maximum tolerated dose by single exposure of therapeutic in increasing concentrations, and determination of suitable dose and treatment schedule for in vivo antitumor study are of high importance for the following in vivo efficacy studies on tumor bearing mice.
Pharmacokinetics: With multiple biosampling, we can follow up concentration, activity, and distribution of your compound over time, allowing us to suggest the best potential treatment regime for efficient therapy.
IN VIVO DRUG EFFICACY STUDIES
In tumor-bearing animals, we can quantify the antitumor activity of your compound, regarding either primary tumor growth or metastatic activity.
In vivo antitumor activity studies
KINETO Lab provides you to investigate the effect of your compounds in animal models which are representative of a variety of solid tumors and hematological malignancies which may be implanted either subcutaneously, orthotopically or into wide range of organs (spleen, breast, stomach, colon, kidneys, cranium etc.). Implantations may be performed by injection of cell suspensions (with or without matrix), by implantation of tumor fragments or by injection of dissociated tumor cells.
Based on in vivo toxicology and pharmacokinetic data, and our extensive experience we suggest the regime of treatment to be performed for in vivo studies: dose, timeline, individual and/ or combinational treatment, control group treatment.
Treatments may be administered per os, intraperitoneally, intravenously, intradermally, intramuscularly, or by direct injection in the tumor. Precise administration modalities will be determined with our partner and written in the study plan.
Our results include the evaluation of tumor volume over time, dissemination to other localizations, determined by imaging or macroscopic/microscopic analyses. During the treatment, we monitor general welfare of the animals, quantified by body weight measurements, which is supplemented by documentation of visible signals (fur, behaviour, injuries, etc.). Tumor growth can be followed also by our in vivo imaging system (IVIS).
At the end point of the experiment we evaluate macroscopic pathological changes on all vital organs as well as presence of metastases in distant organs, lymph nodes, and in the close proximity of the primary tumor. We measure weight of harvested tumor and particular organs, and flash-freeze them, or put them in formaldehyde for further ex vivo examination.
In vivo antimetastatic studies
KINETO Lab offers spontaneous models of metastasis where tumor cells have to complete all steps of the metastatic process with next sites of injection of target organs:
- subcutaneous tissue (lung)
- spleen (liver, lung)
- hind leg muscle (lymph node, lung)
while it is possible orthotopical transplantation of tumor cells into next target organs:
- wall of large bowel (liver)
- kidney (lung),
- mammary fat pad (lung, liver, kidney, spleen, lymph node)
- dermis (lung, lymph nodes)
additionally, we provide experimental models of metastasis with next sites of injection:
- tail vein (lung)
- portal system, (liver)
- carotid artery, (brain)
- left ventricle of the heart (all organs)
model which is used to accelerate metastasis formation:
after several days we remove the primary tumor, and therefore we are able to accelerate metastasis formation.
IN VIVO IMAGING SYSTEM (IVIS®)
During in vivo studies, we can obtain additional visual information of tumor growth and drug uptake.
KINETO Lab has in vivo imaging system (IVIS®, PerkinElmer) with leading technology for preclinical imaging research and development ideal for non-invasive monitoring of tumor growth and compound in vivo uptake studies by which has access to the following modalities:
- Micro CT