Smarter™ Universal ZipCAR Development

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

As a leading service provider in the field of antibody discovery and immunotherapy for years, Creative Biolabs now presents a superior universal chimeric antigen receptor (CAR) system for enhancing the safety and specificity of CAR-T cell therapy. This system has a powerful application in integration signals from multiple antigens and fine-tuning T cell activation in a cell-type-specific manner.

Background

It is a popular and promising approach to transfer CAR-T cells to patients for cancer immunotherapy. However, the rigid design of the CAR-T cells used in clinical trials today limits the re-engineering of T cells and controllability of CAR-T cell activation levels. Therefore, it is quite challenging to manage CAR-T cell-related toxicities. Besides, the antigen specificity and affinity are also affected by the fixed CAR design. Safety and efficacy are two of the major hurdles that hinder CAR-T cell therapy development. To get rid of the situation, we developed the universal CAR system to finely tune T cell activation, enhance tumor specificity, and independently control different signaling pathways and cell types.

Introduction of Universal ZipCAR Technology

The universal CAR system consists of two components, one is a universal receptor (zipCAR) expressed on T cells and the other is a tumor-targeting scFv adaptor (zipFv) (Fig 1). Compared with the conventional fixed CAR, the universal CAR is designed to allow targeting of multiple antigens without further genetic manipulations of a patient's immune cells. Meanwhile, the universal CAR has multiple tunable variables and thus being more attractive. For example, the affinity between leucine zipper pairs, the affinity between tumor antigen and scFv, the concentration of zipFv, and the expression level of zipCAR are all tunable and can be used to modulate the T cell response. Notably, it was found that the affinity between leucine zippers has a good correlation with cellular activation regarding cancer cell killing efficiency and cytokine secretion. Moreover, the universal CAR components can be humanized and reduce potential immunogenicity using leucine zipper domains derived from human transcription factors.

Comparison between the conventional CAR (left) and universal CAR (right) design.

Fig 1 Comparison between the conventional CAR (left) and universal CAR (right) design. (Cho JH, et.al. 2018)

Highlight Features of Our Service

Ph.D. level scientists and skillful technicians
Rich experience and advanced platforms
Time- and labor-saving
Superior quality

With years of extensive experience in the field of immunotherapy, Creative Biolabs has won a good reputation and established cooperation with numerous worldwide customers. We promise timely troubleshooting to guarantee the highest success rate of every project. We are dedicated to facilitating your projects and pushing the progress towards clinical trials through sharing our technologies, platforms, and resources. Please feel free to contact us for more details and our team will get back to you as soon as possible.

Reference

Cho J H, et al. (2018). Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses. Cell. 173(6), 1426-1438.