Chimeric Autoantibody Receptor (CAAR)-Engineered Tregs for Autoimmune Diseases Therapy

Based on a pathogenic mechanism, chimeric autoantibody receptor T cell (CAAR-T) treatment and chimeric antigen receptor-regulatory T cells (CAR-Tregs) treatment are chimeric antigen receptor T cells (CAR-T) -derived immunotherapy for autoimmune diseases (AIDs). Creative Biolabs has broad technological expertise that allows us to develop original formulations and design beat solutions that are easy to use in research. We offer a range of customized services, such as CAAR-engineered Tregs development services to advance the basic research and therapeutic strategy development of AIDs.

Chimeric Autoantibody Receptor T Cell (CAAR-T)

Scientists engineered human T cells to express a chimeric autoantibody receptor (CAAR). The general method is to fuse this receptor consisting of the pemphigus vulgaris (PV) autoantigen, desmoglein (Dsg) 3, to CD137-CD3ζ signaling domains. Because Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand persistently, it specifically eliminates Dsg3-specific B cells in vivo.

With a forward-looking insight and intuition, Creative Biolabs has equipped with advanced instruments, fit-for-purpose laboratories, and professional scientists to provide customized, one-stop solutions of chimeric autoantibody receptor (CAAR)-engineered Tregs development services for our global customers. We can engineer human T cells to express a chimeric autoantibody receptor (CAAR) and guarantee that the engineered key epitopes of the CAAR are correct, and the sequence and molecular structure of the specific antigens are clear. It is our commitment that the engineered epitopes can be recognized by cognate autoantibodies from patients, which is a precondition before using CAAR-T cells to treat antibody-mediated AIDs.

Fig.1 Schematic of native Dsg3, Dsg3 CAAR, and lentiviral vector for stable CAAR expression. (Christoph, 2016)

Chimeric Antigen Receptor Regulatory T Cells (CAR-Tregs)

CAR technology and its application to Tregs has garnered huge interest among researchers in the field of cell and gene therapy. Merging the benefits of CAR technology with Tregs offers a novel and promising therapeutic option for the durable reshaping of undesired immune responses following solid organ or hematopoietic stem cell transplantation, as well as in immune-related disorders.

Creative Biolabs provides CAR-Tregs development services to promote the advance of autoimmune disease research. We have professional processes and personalized services to meet the needs of high-end customers.

• Isolation

The isolation step would benefit from currently available, functionally closed and automated good manufacturing practice (GMP)-grade sorting systems, as well as standardized quality control (QC) tests for impurity testing.

• Activation

Activation and stimulation of Tregs under ex vivo conditions should rely on a combinatorial approach applying GMP-grade magnetic bead systems that have already been established for CAR-Tregs cell manufacturing, and (high) exogenous interleukin-2 (IL-2) stimulation.

• CAR-Tregs design and gene delivery

Our professional research team has many years of experience in the field of cell generation. We design CAR-Tregs characterized by high specificity, high affinity, and rapid expansion. The obtained Treg master product further undergoes genetic modification with a CAR construct using a GMP-grade vector.

• Expansion

Expansion processes should be conducted in full GMP-compliant rocking-motion bioreactors with GMP-grade culture bags. These systems enable continuous nutrient supply and waste removal; they are also more efficient, less prone to contamination, and probably introduce less batch-to-batch variability.

• QC assays formulation and filling

Media perfusion systems are also compatible with magnetic bead activation. This approach reduces the loss of Tregs and antibodies because the application of a magnetic field can retain both. Finally, the formulation and filling processes should comprise GMP-compliant medium compositions and filling devices for batch production, and consistent in-process and release testing, as well as standardized assays for impurity testing.

Fig.2 Current Manufacturing Workflow of Conventional Polyclonal Treg Cells. (Fritsche, 2020)

We have witnessed too many failure cases of the project due to a lack of detailed knowledge. So, Creative Biolabs deeply rooted in the research of CAAR-engineered Tregs preparation and regulation for many years, and have accumulated rich experience and expertise to better serve our global customers. If you want to get more information about our services, please feel free to contact us.

References

1. Christoph, T.; et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016, 353(6295).
2. Fritsche, E.; et al. Toward an Optimized Process for Clinical Manufacturing of CAR-Treg Cell Therapy. Trends in biotechnology. 2020.

For Research Use Only | Not For Clinical Use