Development of Cell-Based Gene Therapies for Rare Diseases
Chimeric antigen receptor (CAR) T-cell therapy is a key example of cell-based gene therapy, combining the technologies of cell therapy and gene therapy. Our company is committed to helping our customers develop next-generation CAR-T and gene therapies for the treatment of rare genetic diseases. With our company's core competencies in translational science and clinical development, we are confident that we can assist you in developing a potential pipeline of first-in-class new drugs and improving the status of your product candidates.
Background
The basis of CAR T therapy is T cells, which play a key role in the immune system. In this therapy, human T cells are modified in vitro by genetic engineering, then infused back into the patient to treat the disease. CAR T therapy has been optimized and modified in recent years to achieve excellent results in tumor treatment. It is considered to be a very promising new tumor immunotherapy method that can be accurate, fast, and efficient, and may cure rare cancers.
Recent studies have shown that CAR T-cell therapy can be modified to treat the rare chronic autoimmune disease myasthenia gravis (MG) in a small animal model. The development of personalized CAR T-like therapies offers the possibility of treating a variety of rare diseases. Currently, CAR-T cell therapy has achieved positive therapeutic results in the clinic, but potential toxicity and drug resistance issues remain a significant challenge. Therefore, it is urgent to accelerate the search for new tumor targets, study the signaling mechanism and develop new technologies.
Fig. 1 Overview of CAR T-cell therapy. (Sur D, et al., 2020)
Our Cell-Based Gene Therapy Development Services for Rare Diseases
Our company is committed to making new innovations and breakthroughs in CAR molecular design, transduction methods, and the selection of optimal cell types to advance cell therapy for rare diseases. We provide technical support and scientific services to help our customers address the challenges encountered in CAR T-cell therapies to accelerate the development of gene therapies for rare diseases.
- Solve the problem of CAR-T cell-related toxicity
Side effects can occur during CAR-T therapy, the most common ones being cytokine-release syndrome (CRS) and neurotoxicity. We offer the following services to help customers reduce the toxicity of CAR-T cell therapies: - Engineering CAR-T cells to reduce toxicity
We provide multiple strategies to reduce toxicity, such as altering the affinity of the antigen-binding domain of CAR-T cells and regulating cytokine secretion through activated CAR-T cells by modifying the transmembrane and hinge regions. - Decreasing CAR immunogenicity
We utilize human or humanized antibody fragments instead of murine-derived CARs to reduce the toxicity caused by the recognition of CAR constructs by the host immune system. In addition, we provide modifications of the hinge and/or transmembrane structural domains to reduce the immunogenicity of CARs. - Modifying CAR transduced T cells
We offer an approach based on modifying CAR-transduced T cells to prevent CAR-T cell cytokine toxicities. - CAR "off-switches"
We offer strategies based on "off-switches" or suicide genes to ameliorate CAR-T cell toxicity. - Solve the problem of resistance to CAR-T therapy
The resistance generated during CAR-T therapy can be divided into two aspects, antigen-dependent and non-antigen-dependent, depending on the mechanism. To address the issue of antigen dependence, we provide the following strategies: - Designing multi-targeted CAR molecules
- Increase the expression of target antigens
- Increase the affinity of scFv to the target antigen
To address the issue of non-antigen dependence, we provide the following strategies:
Blocking immunosuppressive checkpoints to stop T-cell depletion, such as by modifying the PD-1 molecule on CAR-T cells.
Improve the proliferation, persistence, and anti-tumor activity of CAR-T cells, such as through expressing IL-7 receptor on CAR-T cells.
- Generalized cell therapy
Generic cell therapy is the way of the future. We help our customers develop universal CAR cell therapies through commonly used gene editing tools, such as ZFN, TALEN, and CRISPR/Cas9.
CAR T Cell Therapy Workflow
With the rich product lines of cell and gene therapy, an advanced technology platform, and a team with a pioneering record in cell-based gene therapy, our company has the strength to cooperate with you and promote cell-based gene therapy for a variety of rare genetic diseases. If you are interested in our services, please contact us for more details.
Reference
- Sur, D.; et al. Chimeric antigen receptor T-cell therapy for colorectal cancer. Journal of clinical medicine, 2020, 9(1): 182.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.