Have you ever wondered what the future of science education looks like? Many envision a future of readily accessible science knowledge and facts presented by intelligent, interactive teachers. Given the limited time and resources available from top teaching talent, there is an increasing demand for engaging scientific learning that could be supported by the growing power of machine learning and artificial intelligence (AI) platforms.
To this end, Cyagen and Cyrinn have combined their expertise to create “AI Marvin,” the world's first AI Chief Scientific Officer to focus on the dissemination of biological science knowledge focusing on genetics research topics. Meet AI Marvin and the man behind the scientific magic, Dr. Ouyang!
Introducing AI Marvin
Our real-life Chief Scientific Officer, Dr. Yingbin (Marvin) Ouyang, not only contributes his likeness, but also imparts his knowledge through AI Marvin’s presentations. Dr. Marvin Ouyang has been dedicated to the development of genetically engineered rodent models for the past 20 years, developing hundreds of transgenic and KO/KI mouse/rat models for biomedical research and drug development. Dr. Ouyang has published many papers in high-impact academic journals such as PNAS and JBC; his technical services have been directly cited hundreds of times by top international journals, including Nature. He has now dedicated significant time to help teach the AI that will serve to educate the masses and provides ongoing support with production of educational topics.
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AI Marvin is the world's first AI Chief Scientific Officer, created by Cyagen and Cyrinn, to focus on the dissemination of biological science knowledge, with a focus on research involving genetically engineered disease models for effective therapeutic evaluations. Through humorous and simple teaching methods, it provides a human connection that stimulates the audience's curiosity and desire for knowledge. This might help people establish a scientific attitude and thinking, facilitating a strong understanding of the scientific process and innovative academic thinking through access to high-quality popular science education. In the future, AI Marvin will also have its own 3D image, which will further enrich the range of content expression and better serve popular science education by appealing to even wider audiences.
QUESTIONS? Ask AI Marvin by tweeting us @CyagenBio with the hashtag #ASKAIMARVIN!
AI Marvin Playlist (YouTube)
At present, cell therapy is mostly used in the field of oncology, in which it is necessary to construct stable tumor cell models and animal models to evaluate the therapeutic effect. Chimeric antigen receptor (CAR) T cell therapy has made great strides in hematological malignancies, with approved therapies in certain leukemias, lymphomas, and more recently myeloma, with very high overall response rates.
In vitro cell models provide a variety of detection methods for evaluating the effectiveness and specificity of CAR-T therapy. For in vivo evaluation models, it is required that the model have a corresponding immune environment to avoid causing CAR T-cell rejection, and the experimental animals must have a stable living condition. In addition, a mouse model of homologous tumor transplantation can also be used to verify the mechanism and treatment principles of CAR-T.
Quick Q&A Series: CAR T Cell Therapy
As one of the fastest growing areas of pharmaceutical research and development, CAR T cell therapies are demonstrating great promise for treating more than just blood cancers. There are many factors that affect the effectiveness of CAR-T cells, such as transfection efficiency, culture conditions, and cell types. In this series, AI Marvin answers many common questions about CAR T cell therapy research.
Subscribe to Cyagen’s YouTube to get notifications for all our new videos, covering scientific topics related to genetic engineering, featured genes, disease pathologies, cell and gene therapy (CGT) research, and CAR-T cell therapy development.
QUESTIONS? Ask AI Marvin by tweeting us @CyagenBio with the hashtag #ASKAIMARVIN!
1. How to Choose CAR-T Target Cells
In some cases, after selecting the indications and targets there are a lack of suitable natural tumor cells as target cells. In this situation, how do researchers select the target cells?
In this case, we can choose to construct a corresponding stable cell line. The selection of the cell line type should be as consistent as possible with the indication and the study. For example, if the indication for the study is liver cancer, a corresponding liver cancer cell line can be selected as the stable cell lines for this study. In this way, the cell line can also be used for downstream in vivo and anti-tumor activity evaluation experiments. In addition, if we only make some simple anti-tumor activity evaluation and specificity verification work we can also choose more commonly used tumor cell lines such as 293T and CHO-K1 these cell lines are easy to be infected by lentiviruses so it is easy to obtain stable cells which can save time and costs.
2. How to Verify the Specificity of CAR T Cells
Bispecific CAR-T cell therapy may often be selected due to the improved cytolytic activity that may be achieved. However, researchers may face a lack of cell lines that co-express dual targets. How do researchers choose the target cell and verify the specificity of the CAR-T cells constructed?
Due to the heterogeneity of target antigen expression in tumor cells and the problem of antigen escape during CAR-T cell therapy, there are more and more studies on bispecific CAR-T to solve this problem. In the absence of suitable target cells for dual-target CAR-T cell research, we can solve this problem by constructing a stable cell line. The cells used to construct a stable cell line may be derived from the adaptation of disease tumor cells. To study the function of bispecific CAR-T cells, we can also construct a cell line with single and dual expressing antigen, So the specificity of bispecific CAR-T cells can be assessed to some extent after lysis of these cell lines in vitro.
3. CAR-T Cells Antigen Loss and Validation of Anti-Tumor Effects
How can we fix the loss of stable cell lines’ surface antigens?
If the stable cell lines have eukaryotic resistance it can be maintained by adding corresponding antibiotics. However the dose of antibiotics needs to be optimized in order to achieve a better maintenance effect, but if not, several times enrichment can be performed by flow sorting, which may solve the problem of antigen loss in stable cells. In addition the cell lines with stable antigen expression can be obtained by screening the clones.
How can we choose the appropriate target cells to prove the specificity of the anti-tumor effect of car T cells?
Well we can both select cell lines that express or not express the target antigen and then use CAR-T cells to kill these two types of cells respectively and according to the killing results determine whether the anti-tumor effects of CAR-T cells is specific or not.
Cell & Animal Models for CAR-T Cell Therapy and Immuno-oncology
As a global research services company, Cyagen provides one-stop research service solutions supporting CAR T and other cell therapy development programs, including: CAR virus preparation, the construction of tumor immune cells and animal models, and the entire process of in vivo/in vitro drug efficacy evaluation. Our services accelerate the development of your CAR T and cell therapy research.
Cyagen has been committed to the establishment of gene-edited cells and animal models. We have an experienced team of experts and a mature technology platform that provides cell models and animal models for the regulation of target gene expression. For CAR-T and cell therapy research, we have established catalogs with thousands of cell and mouse models for tumor immune research, and provide preclinical in vivo/in vitro pharmacology evaluation services for domestic and foreign pharmaceutical companies, biological companies, scientific research institutes, and hospitals. For example, C-NKG mice are a severe combined immunodeficiency (SCID) model developed by Cyagen, which are without murine T/B/NK cells and have defective myeloid components. C-NKG mice can be used to construct various CDX models and reconstruction of the human immune system in a mouse model.
In vivo Evaluation Models
Animal Model Services：
- Immunodeficient Models: BALB/c nude mice, NOD scid mice, C-NKG mice
- Humanized immune system (HIS) models: Hu-PBMC mice, Hu-HSC mice
- Cell Line-derived Tumor Xenograft (CDX) models: Subcutaneous solid tumor model, In situ solid tumor model, Hematoma model
- Homologous tumor mouse models: Lung cancer, colorectal cancer, breast cancer, melanoma, and other homologous tumor models
Advantages:
Cell Line-derived Tumor Xenograft (CDX) models
- The mechanics of tumor formation among a variety of tumor cells can simulate solid tumors and hematomas.
- It can effectively support the growth of various tumor cells and CAR-T cells.
- The CDX model is stable, the experiment is highly reproducible, and the result data is reliable.
- Highest standards across animal experiment operations and breeding environment.
Humanized Immune System (HIS) Models
- The survival rate of mice is high, and the experimental window is long.
- Different reconstruction methods of PBMC and HSC can be provided with a high degree of humanization.
- The model has high uniformity and the data is more convincing for translational research.
In vitro Evaluation Models
Cell Model Services：
- Tumor cells expressing CAR-T targets
- Luciferase labeled tumor cells
- CAR-T cell construction
- Overexpression stable transgenic cell Line services
Advantages:
- Antigen expression is stable: The degree of antigen expression is high, and it still maintains stability after multiple passages.
- High expression efficiency of CAR molecules: All T cell subtypes have significantly high expression of CAR molecules.
- One-Stop Services: Multiple verification schemes, complete model construction and identification system.
For more information, contact our experts to inquire about our services or obtain a quote for your project.
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Original Article