CAR-T Cell Therapy with CRISPR Platform

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

With the aid of superior technologies and skillful scientific teams, Creative Biolabs has been a well-known service provider in the field of antibody discovery and immunotherapy. Now, we are proud to present a powerful platform combing Chimeric Antigen Receptor (CAR) T cell therapy with the Clustered, Regularly Interspaced, Short Palindromic Repeats-associated endonuclease 9 (CRISPR/Cas9) technology to our worldwide clients, aiming to push their projects closer to clinical trials.

1. Background

With the approvement of two CAR-T cell therapies, CAR-T cell therapy is transforming the treatment of certain cancers, such as blood cancers. By giving immune cells the information they need to better recognize tumor cells as foreign and attack them, this kind of targeted immunotherapy aims to boost the immune systems. Currently, CAR-T cells are usually made through a retroviral or lentiviral technology to deliver the CAR gene into the T cells. However, this delivery approach could possibly result in the CAR gene being inserted at random into the genome of the recipient cells, which can result in unwanted genetic side effects. Aided by CRISPR/Cas9, a robust genome-editing tool with high precision, the CAR approach can create CAR-T cells with more stamina - they can kill tumor cells for longer because they are less prone to becoming exhausted. Our novel platform could eventually lead to safer, more effective use of this powerful form of immunotherapy in patients.

2. Application of CRISPR/Cas9 in CAR Therapy

Creative Biolabs has developed several innovated approaches to combine CRISPR with CAR therapy.

a. It is often difficult to obtain enough T cells with good quality to generate patient-specific CAR-T cells for newborn and elder patients. Therefore, an allogeneic adoptive transfer strategy is highly desired, in which universal CAR-T cells can be derived from healthy donors and applied to treat multiple patients. In this situation, our platform can use CRISPR technology to eliminate the αβ T-cell receptor (TCR) on allogeneic CAR-T cells to avoid graft-versus-host-disease (GVHD). Meanwhile, human leukocyte antigens class I (HLA-Is) on CAR-T cells can also be removed to minimize their immunogenicity.

b. Considering blocking programmed death-1 (PD-1) signaling can effectively treat cancers via reversing immunosuppression, we are also capable of targeting PD-1 in CAR-T cells to render them nonresponsive to PD-1 signaling. Other T cell inhibitory signaling molecules can also be modified in this way.

c. Notably, these Cas9-based gene-editing techniques can also enable the disruption of the virally targeted chemokine receptors in T cells. Thus CCR5 and CXCR4 can be eliminated from the T cells for HIV patients.

To generate universal and more potent CAR-T cells, 2-5 genes can be eliminated simultaneously by incorporating CRISPR. This combination platform in Creative Biolabs will involve in the evolving field of next-generation CAR-T cell production for therapeutic purpose. Our Ph.D-level scientific team will provide timely troubleshooting to guarantee the highest success rate of each project. If you are interested in any of our services, please feel free to contact us for more details. Our team will get back to you as soon as possible.