Creative Biolabs has a tradition of commitment. To achieve efficient execution and regulatory approval, we offer careful considerations of your program for the development of a cellular or gene therapy product – now and in the future.
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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.
Removal of CAR-T cells is a useful way to limit the adverse effects post CAR-T cell therapy; however, it terminates the anti-tumor clinical effects at the same time. Off-tumor toxicity can be inhibited by enhancing the specificity of CAR-T cells. With proper design, CAR-T cells are able to exhibit activity only in response to a particular combination of dual tumor-associated antigens that are co-expressed by tumor targets. The dual CAR-T cells express two kinds of CARs, one of which recognizes and binds to one tumor-associated antigen and transmits only the primary signal, while the other recognizes a distinct tumor antigen and transmits the co-stimulatory signal. Therefore, dual CAR-T cells show activity only under the presence of both targets on the tumor and thus possess improved safety.
For example, one type of design for dual CAR-T cells is that T cells co-expressing anti-ErbB2 and anti-MUC1 specific CARs use CD3ζ and CD28 signaling pathways, respectively. These dual CAR-T cells kill ErbB2+ tumor cells efficiently and proliferate in conditions that requires co-expression of MUC1 and ErbB2 by target cells. In another example, T cells are genetically modified to co-express signal 1 (Anti-Meso scFv-CD3ζ) and signal 2 (Anti-Fra scFv-CD28) CARs. These CAR-T cells show weak cytokine secretion against target cells expressing only one tumor-associated antigen in vitro, which is similar to first generation CAR-T cells bearing CD3ζ only, but demonstrate enhanced cytokine secretion upon encountering natural or engineered tumor cells co-expressing both antigens. The dual CAR approach potentiates the therapeutic efficacy of CAR-T cells against cancers while minimize parallel reactivity against normal tissues bearing single antigen.
As the leading biotech company in CAR-T cell therapy, Creative Biolabs focuses on some urgent questions and try our best to overcome these problems. We have developed multiple novel 4th generation CAR technologies and provide SmarterTM Dual CAR construction service to help our clients to develop a safer CAR-T therapy with improved anti-tumor effects.
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CellRapeutics™ In Vivo Cell Engineering: One-stop in vivo T/B/NK cell and macrophage engineering services covering vectors construction to function verification.
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Silence™ CAR-T Cell: A novel platform to enhance CAR-T cell immunotherapy by combining RNAi technology to suppress genes that may impede CAR functionality.
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Canine CAR-T Therapy Development: From early target discovery, CAR design and construction, cell culture, and transfection, to in vitro and in vivo function validation.
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