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In the context of cancer research, a human tumor sample is implanted into immunocompromised mouse or rat, which allows for the study of the tumor’s growth and response to treatment in a living system (called PDX xenograft). These animal models are used to test the efficacy of new drugs, test efficacy of known chemotherapy for individual patient (personalized oncology), and in cancer research to study the underlying mechanisms of tumor growth and metastasis. The process of xenotransplantation involves surgically implanting a small piece of tumor tissue from a human patient into an animal, often into the subcutaneous tissue or a specific organ. Once the tumor has been successfully engrafted, it is studied over time to track its growth and response to treatment.
Chemotherapy treatments often vary in terms of effectiveness; there are many drugs on the market, and depending on the individual some may be better than others. To ensure that the right chemotherapy is chosen for a given patient, Altogen Labs has developed a patient-derived xenograft (PDX) that can prove to be life-saving for cancer victims. Made with tissue extracted from a patient’s tumor, a PDX model will respond to drugs in the same way that the patient would, showing which treatment will be most effective. Altogen Labs has had decades of combined experience in xenograft testing, and patients can feel assured that they will be undergoing the therapy that is best for them. To begin the PDX process, patients should contact Altogen Labs with information about their cancer and current treatment. From then on, Altogen Labs will work with the patient’s hospital to obtain a tissue sample of the tumor (recent biopsy sample can be used in some cases), after which company scientists will grow the tissue, and within a few months results will be given to the patient’s doctor for treatment development. The results will clearly indicate effectiveness of specific chemotherapy against patient cancer cells, which chemotherapy is the most efficient and what chemotherapy will not work at all (depending on cancer type and individual response to specific chemotherapy, there are many common cases when patients have cancers that do not respond to chemotherapy). Although the cost of PDX models can be substantial, Altogen Labs strives for reasonable prices, helping customers find options suitable to their resources. Chemotherapy can be successful, so long as it is tailored to the patient. Further details are given below, with more information on Altogen Labs’ website.
Our technology requires that fresh (live) tissue be implanted into immunocompromised mice (we use NOD/SCID and NU(NCr)-Foxn1 nude mice strains). We prefer metastatic tissue over primary tissue, but we will accept either. For a biopsy samples we request four (4) core biopsies that are at least 10 mm in length via an 18-gauge needle and for surgical cases we request a half to a full cubic centimeter of tissue. Ideally, the biopsy or surgery should be scheduled early morning to allow for the majority of tumor transportation to occur during business hours.
The entire xenotransplantation (patient tumor tissue implantation in mice and expansion) and chemotherapy testing process takes 14-18 weeks. The first generation of tumors grow to full size within 2-3 months, at that time they are harvested, divided into smaller tumor tissue pieces, and re-implanted into new set of immunocompromised mice. Chemotherapy treatments are initiated as soon as measurable tumor growth is detected (3-5 days) and continues for 25-30 days. Therefore, total process takes 8-12 weeks to grow first generation tumors + 5-6 weeks for tumor re-implantation and chemotherapy testing. The results are usually available within 14-18 weeks after project initiation.
The initial tissue shipment and implantation fee is $2,500. After tumor growth established and patient confirm interest in proceeding to chemotherapy sensitivity testing, the next payment would be dependent upon the number of chemotherapy drug tests performed. We recommend testing at least 5 chemotherapy compound and 2-3 combinations. The pricing structure is as follows:
| Test(s) | Total Cost ($) |
| 1 | 5,800 |
| 2 | 8,600 |
| 3 | 11,400 |
| 4 | 15,200 |
| 5 | 18,800 |
*Each additional test is $2,500 per test
NOTE:
Please consult your doctor (oncologist) in regards to your cancer type and associated list of chemotherapy drugs that should be tested.
Description of Patient-Derived Xenograft Services provided by Altogen Labs:
Introduction
Chemotherapies are often based on evidence obtained from clinical trials. Although various drugs can show positive effects in many patients, specific, patient-centered treatments require individual testing. A xenograft provides this opportunity by allowing for various drugs to be tested in an environment outside of the patient. This is done by implanting a piece of a patient’s tumor in a mouse, letting it grow, and testing drugs on the tumor. Results from the testing can show which chemotherapies are most effective at combating a given patient’s cancer. These results may prove life-saving, as patients will know exactly which drug can fight best against their specific cancer.
Process Overview
There are several steps in the process of obtaining a patient-derived xenograft. First of all, a tissue sample from a patient’s tumor must be obtained. It is preferable that the patient be off chemotherapy for at least a few weeks before the extraction, as this will aid in the specificity of drug testing results. Secondly, the tumor tissue sample (once extracted) must be implanted in a prepared donor mouse. After this is done, the tumor sample is grown in the mouse until the tumor reaches a suitable size (around 6-8 weeks). If multiple drugs are to be tested, the tumor is divided into several parts, and re-implanted in other mice for subsequent testing. Once a tumor has reached the necessary size threshold, a drug chosen by the patient and their oncologist is tested on the tumor. If a selection of drugs is chosen, then each drug is tested separately in different mice. The results are then obtained through quantitative analysis of tumor growth. The drug(s) that are most efficient at limiting or killing the tumor are then presented to the patient and their oncologist. Based on patient history, the oncologist will select an efficient drug that is unlikely to result in a negative reaction from the patient. This drug then becomes the foundation for a patient-centered chemotherapy program.
Tumor Extraction Specifics
Tissue samples may be obtained from a patient during a biopsy or surgery. If the patient already has such a procedure scheduled, then it is strongly advised for the tissue sample to be obtained then. Although being off chemotherapy may aid in result specificity, it is more imperative to have the sample obtained quickly so that the implantation and growth processes may begin.
During a biopsy or surgery, the doctor will be given specific protocols for tissue extraction. The sample will be obtained and immediately sent to a clinical laboratory where prepared mice await tissue implantation.
Patient Responsibilities
The patient must consent to tissue extraction and have a sample of their tumor collected, either during a normal surgical procedure (such a biopsy) or a specifically scheduled procedure for tissue collection. After the tissue is collected, the patient is free to continue their previous chemotherapy, as there will be no further need to collect tissue samples. The xenograft and drug testing will be conducted in a clinical laboratory.
The patient has the choice of selecting the drugs to be tested. They may also request for a sample of their tumor to be cryogenically frozen and thus preserved in the case that future testing may be necessary. This may be advantageous for later-stage cancers, which may reoccur even after local removal. In the case that a cancer reoccurs in a patient, the previously frozen sample may be thawed and grown successfully in a donor mouse. This process takes considerably less time than the first xenograft, and can help quickly determine other potential chemotherapies for the patient.
Pros and Cons of Xenografts
A patient-derived xenograft is capable of giving invaluable data on the efficacy of various drugs on an individual cancer. This allows for the selection of a chemotherapy that is best-suited for an individual patient, and can help eliminate the chance of ineffective treatments. The simultaneous testing of multiple drugs expedites the process of finding the most effective chemotherapy. If the cancer of a patient is in an early stage, the results from such testing can help prevent intrusive treatments such as surgical removal of a tumor. Later-stage cancers can still be contained by effective chemotherapies, and even eliminated by drugs that prove to be adept at fighting a patient’s specific cancer.
Perhaps the only problem with patient-derived xenografts is the time it takes for results to be acquired. Tissue samples must be grown in mice until they can serve as reliable targets for drugs, and the process can take several months. Previously, one of the main issues with xenografts was the natural immune system of mice acting against implanted tissue samples. Today, such issues have been resolved through the advent of immunodeficient mice, and even mice with human-adapted immune systems. These breakthroughs in clinical testing have provided environments for drug testing that are nearly equivalent to humans, making the results of such testing all the more reliable.
Costs
Clinical monitoring of mice, the growth of tumors, and reliable drug testing all require significant resources. Unfortunately, insurance companies largely do not cover such individual-based treatments. However, the process is designed to be relatively affordable. For the testing of a few drugs, a patient-derived xenograft will cost approximately the same as a course of chemotherapy.
Please contact us directly or ask your physician to contact us at info@altogenlabs.com to discuss how Altogen Labs PDX tumor models can become part of your cancer treatment solution.