As one of the current most popular immunotherapies, CAR-T therapy shows its strength by boosting the patients’ own immune system to destroy the cancer. Creative Biolabs provides a comprehensive series of services in cellular and gene therapies including T Cell Receptor (TCR) T cell therapy, CAR-T cell therapy, CAR-macrophage cell therapy, Chimeric Antigen Receptor (CAR) NK Cell Therapy supported by our multidisciplinary team with flexible solutions. We can accommodate the specific properties of your product and provide flexible integrated solutions.

Fig.1 Treatment of patients with B-cell malignancies using anti-CD19 CAR T cells. (Klebanoff, 2014)

Chimeric antigen receptors (CARs) are recombinant receptor constructs which are composed of an extracellular single-chain variable fragment (scFv) derived from an identified antibody specific for tumor neoantigen, joined to a hinge or spacer peptide and a transmembrane domain, which is further linked to the intracellular T cell signaling domains of the T cell receptor. Combining the specificity of an antibody with the cytotoxic and memory functions of T cells, CAR-T cell therapy shows powerful and promising therapeutic functions for cancer treatment in high affinity without MHC dependent requirement (see Fig.1).

Fig.2 Structural components of CAR (left) and gene modified CAR-T cell therapy(right). (Harris, 2016; Garber, 2018)

CAR-T cell therapy has been considered the most significant therapeutic advance in a generation. To develop CAR-T based approaches, Creative Biolabs offers an end-to-end integrated solution covering all steps prior to clinical trials (see Fig.2). You can start at any module and request a flexible integration of different modules to fit your projects. Both engineering services for αβ T cell and γδ T cell derived from patients and normal populations can be achieved.

Fig.3 Process of CAR-engineered T cell therapy.

Neoantigen Identification

With multiple gene and protein analysis technologies, we offer unique de novo neoantigen discovery, identification, selection to get a suitable CAR-T therapy target with high potency and low toxicity.

scFv Generation and Optimization

Aided by our in-house antibody database and various types of libraries including hybridomas, mouse, rabbit and human, plus scFv sequencing and affinity measurement platforms, we are dedicated to generating the most optimized scFv with high affinity and good properties.

CAR Design Construction and Plasmid GLP Production

We are capable of designing and constructing different generations of CARs, also various types of engineered CARs are available at Creative Biolabs, such as suicide CAR, inducible CAR, enhanced CAR, bispecific CAR, synNotch CAR, masked CAR, oxygen-sensing CAR, etc.

CAR-T Preparation

With various transfection technologies including electroporation, as well as cell transduction though adenovirus, lentivirus retroviral, etc., we offer CAR gene packaging and delivery services for CAR-T cell generation. To facilitate your drug development, both GLP and GMP level can be achieved to fit your purpose of the project.

CAR-T In Vitro Validation

For generated CAR-T products, a wide range of in vitro assays are available to evaluate the efficiency of CAR-T product, including CAR expression validation, CAR-T cell proliferation, cytokine release assay, cytotoxicity assay, etc.

CAR-T In Vivo Testing

Once in vitro assays are completed, a series of in vivo testing systems will be performed to evaluate the CAR-T product, including animal models, biodistribution studies, efficacy testing, toxicology assessment and other GLP compliant assays.

Fig.4 End-to-end CAR-T Integrated Solutions.

Highlights of Our CAR-T Therapy Program

• Expertise: with in-depth knowledge and experience in cancer therapies;
• Collaboration: our multidisciplinary team is composed of clinicians, hematologists/oncologists, pulmonologists and cardiologists;
• Research: our researchers are figuring current scientific questions including testing combination therapies, improving the effectiveness of novel therapies, and the mechanism why some patients respond better to immunotherapies;
• Therapy option: we also provide drug development programs including antibodies, vaccines, small molecules and others designed to stimulate the immune system to eliminate various types of cancer. Our experts will accommodate the characteristics of your project and design the most appropriate treatment option for you.

With the commitment of being your best CAR-T therapy partner, Creative Biolabs has established the utmost efficient integrated solutions to innovate and accelerate your drug developments for various types of cancers especially the hematologic malignancies. Please feel free to contact us to get more information and a quote for any CAR-T therapy module.

References

1. Harris, D.T, and Kranz, D.M, Adoptive T Cell Therapies: A Comparison of T Cell Receptors and Chimeric Antigen Receptors. Trends Pharmacol Sci. 2016, Mar;37(3):220-230.
2. Garber, K., Driving T-cell immunotherapy to solid tumors. Nat Biotechnol. 2018, Mar 6;36(3):215-219.
3. Klebanoff, C.A., et al. Immunotherapy: Treatment of aggressive lymphomas with anti-CD19 CAR T cells. Nat Rev Clin Oncol. 2014, Dec;11(12):685-6.

For Research Use Only | Not For Clinical Use