Immunotherapy, by stimulating or modulating human immune response to attack malignant tumor cells, has become a promising strategy for future cancer treatments. Preclinical studies using small animal models that support engraftments of clinically relevant human tumor cells would certainly benefit the development of immune-oncology based drugs or cell therapy. Immunodeficient mice or rats lack functional lymphocytes and have defective innate immunity. Engraftment of human tumor samples in these immunodeficient small animals provides optimal model for preclinical studies for immune-oncology therapy.
Creative Animodel offers customized services for establishing human tumor xenograft animal models for CAR-T in vivo preclinical studies. Our experienced scientists and service team will assist you in both animal model construction and experimental design for testing the efficacy and toxicity of your CAR-T therapy.
Immunodeficient models available:
|Mouse||NPG (NOD-Prkdcscid IL2rgnull)|
|NRG (NOD-Rag1null IL2rgnull)|
Types of xenograft models:
Tumor cell line derived xenograft model
Tumor cell lines expressing CAR-T targeting epitopes are usually the first choice testing the efficacy of antigen specific CAR-T therapy. It is relatively easier to develop xenograft models using already established cell lines and these models also have the advantages of low variability among the testing animals. However, compared to patient-sample-derived xenograft models, tumor cell lines lack the heterogeneity characteristics that present in the tumor samples, and therefore less clinically relavent.
Figure 1. Tumor Cell line derived xenograft model
Engraftment with hematopoietic cancer cell lines, such as K562 or NALM-6, provides stable models for testing therapies against hematopoietic tumors. Flow cytometry analysis of peripheral blood and bone marrows will be used to assess successful engraftment.
Solid tumor xenograft
Engraftment of established solid tumor cell lines, including breast cancer, ovarian cancer, lung cancer, etc. are useful models for evaluating therapies against solid tumors. Tumor cell lines can be modified to express Luciferase, which allows bioluminescence imaging monitoring of tumor sizes during CAR-T therapy.
Patient samples derived xenograft (PDX) models
Xenografts models using patient tumor samples retain the original tumor heterogeneity and are histologically most relevant to clinical tumors samples. These models are best for therapeutic evaluation of personalized medicine generated based on patients’ own T cells. Compared to cell line based xenograft models, variability among testing animals is larger for PDX models. It takes more time to develop PDX models and the number of models that could be established for each patient is limited to the amount of samples provided.
Figure 2. Patient tumor derived xenograft model
Establishing xenograft tumor model is the first step for our CAR-T in vivo preclinical study. Creative Animodel offers following services.
✓ CAR-T cells biodistribution or serum persistence
✓ CAR-T cells tumor targeting efficacy
✓ CAR-T cells toxicity evaluation
Our state-of-the-art technology and experienced scientific team will fast advance your CAR-T through clinical trials.