CAR-T Platform

Immunotherapy has emerged as one of the most promising approaches for the treatment of cancer. T cells (T lymphocytes), the armed forces of our immune system, constantly look for foreign antigens and must discriminate abnormal (cancer or infected cells) from normal cells. Genetically modifying T cells with Chimeric Antigen Receptors (CAR)s is the most pursued approach to generate tumor-specific T cells. CAR-T cells targeting tumor-associated antigens can be infused into patients and attack the tumor.

 

ProMab Biotechnologies Custom Chimeric Antigen Receptor Cell Engineering: A complete service, from antigen to clinically relevant solution.

ProMab Biotechnologies (PMB) has developed many CAR-T products based on nearly 20 years' experience on hybridomas, monoclonal antibodies (rabbit, mouse, and human), recombinant proteins, and cancer stem cells. PMB's new custom CAR-T service is designed to take advantage of the astonishing clinical breakthroughs of CAR-T cells against various hematological malignancies.

PMB can construct CARs based on your antibody sequence or can generate a mouse or fully human single-chain variable fragment (scFv) for the CARs. PMB has generated more than 30 types of CAR-T and CAR-NK cells targeting different tumor cells and cell lines expressing tumor-specific antigens.

These CAR-T cells can be used with immunological modulators, tumor microenviroment invaders, or checkpoint inhibitors. In addition, PMB has developed sensitive real-time cytotoxicity assays (RTCA) for CAR-T cell validation in vitro and ex vivo. ProMab has also developed in vivo NSG/ NOG xenograft models to test CAR-T cell anti-cancer activity in hematological and solid cancers.

Here we outline 8 components to a successful CAR platform:

ProMab Biotechnologies has a collection of >3,000 antibody products. The high-throughput flow cytometric screening of hybridomas identifies high-binding antibodies for immunotherapeutics.

From the development of an antibody hybridoma, we are able to sequence and isolate the scFv sequence.

The scFv sequence is inserted into a lentiviral vector along with CAR domains of your choosing. High- titer virus particles are prepared and titered by qRT-PCR.

Primary T cells are activated, transduced by the CAR-encoding lentivirus and expanded in culture for two weeks. ProMab has generated >30 types of CAR-T cells and target cells.

The RTCA assay provides highly sensitive real-time measurements of CAR-T cell cytotoxicity against target cells at different E:T ratios. CAR-T cells produce IFN-γ and other cytokines in response to target cells.

Label-free high-throughput Octet ForteBio binding assays. Affinity maturation and humanization of antibodies are available to increase antibody affinity. Bioinformatics and computer modeling generate humanized and affinity-tuned antibodies.

NSG/NOG xenograft survival and imaging studies characterize CAR-T cells in vivo. Toxicology tests measure the toxicity of the CAR-T cells in vivo.

ProMab manufactures QA-validated CAR-T cells and access to GMP facilities.

Mouse monoclonal antibodies

 
 

Human monoclonal antibodies

 
 

Hybridoma Sequencing