CellRapeutics™ In Vivo CAR-T Cell Engineering Services

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

The Rationale of CAR-T Development

CAR-T cell therapy has made great achievements in the past decade, while conventional CAR-T cell therapy also has some obstacles to overcome, such as the CRS and ICANS toxicity, and the expensive and complex manufacturing process. The in-vivo CAR-T cell engineering by nanoparticles carrying CAR genes and gene-editing tools has shown potential breakthroughs in overcoming the above obstacles of traditional CAR-T cell therapies. Therefore, there is more urgent to develop safe and simple in-vivo CAR-T cell engineering solutions.

Fig.1 Comparison of generating CAR-T in-vitro and CAR-T in-vivo. (Xin, et al., 2022)

Our In Vivo CAR-T Cell Engineering Services

To overcome the limitations of current CAR-T therapy, Creative Biolabs has developed one-stop in vivo CAR-T cell engineering services to support global customers. Our in vivo CAR-T cell engineering carries engineered CAR genes through delivery systems (such as non-viral or viral systems) characterized by multiple functions to overcome the obstacles of current CAR-T, such as CRS & ICANS toxicities, immunosuppressive microenvironments, and complex manufacturing processes.

Highlights of Our Services

Our in vivo CAR-T cell engineering services have the following characteristics.

Special CAR Structure for In Vivo CAR-T Cell Engineering Services

Our CAR structure incorporates special cytokine genes that enable the CAR-T cells to secrete cytokines and flush out the immunosuppression microenvironment, which makes it suitable for T-cell survival and proliferation. There are some cytokine types to design for, including but not limited to: IL-7, IL-12, IL-15, IL-18, IL-19, IL-23;

Modified Delivery Systems to Aid In Vivo CAR-T Cell Engineering

The delivery system plays an important role in achieving specific and efficient in vivo T cell transduction, which can greatly enhance the in vivo generation and anti-tumor activity of CAR-T cells. Creative Biolabs offers the following two modified delivery systems to support our customers' projects.

In Vivo Non-viral CAR-T Cell Engineering Services

In Vivo Viral-based CAR-T Cell Engineering Service

Published Data

Paper title: Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering

Summary: Researchers established a lentiviral vector-based platform for in vivo CAR-T cell engineering: UB-VV100. Which encodes a 2^nd CD19-targeted CAR displayed an anti-CD3 scFv on the surface with a rapamycin-activated cytokine receptor (RACR) system additionally designed for the treatment of B-cell malignancies. The study found that this strategy produced functional CAR-T cells with favorable biodistribution characteristics in vivo.

Technology: lentiviral-based CD19 CAR vector for in vivo CAR T-cell engineering;

Tumor Type: B-cell malignancy;

Results:

Fig.2 Structure Overview of lentiviral-based 2^nd CAR vector (UB-VV100) for in vivo CRT engineering. (Michels, et al., 2023)

Fig.3 UB-VV100 generates functional CAR-T cells from patient PBMC samples. (Michels, et al., 2023)

Fig.4 UB-VV100 mediates depletion of B cells in CD34-humanized NSG mice with a favorable biodistribution profile. (Michels, et al., 2023)

Frequently Asked Questions

Q1. For in vivo CAR-T engineering development, which stage is more challenging and important in the development?

A: In the development, CAR design & construction, the selection of a modified delivery system seems to be critical to the overall development, optimized CAR construction and the modified delivery system could achieve specific and efficient in vivo T cell transduction, greatly enhancing the in vivo CAR-T generation and anti-tumor activity. Based on these factors, we offer several choices for our customers, such as surface-engineered vectors, and modified mRNA delivery systems.

If you are interested in our CellRapeutics™ in vivo CAR-T cell engineering services, please feel free to contact us to learn more.

References

Michels, K.R.; et al. Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering. J Immunother Cancer. 2023,11(3):e006292.
Xin, T.; et al. In-Vivo Induced CAR-T Cell for the Potential Breakthrough to Overcome the Barriers of Current CAR-T Cell Therapy. Front Oncol. 2022,12:809754.