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Immunotherapy Improved CART Therapy

Improved CART Therapy

Immunotherapy has shown tremendous potential in clinical disease treatment; however, severe adverse effects are associated including cytokine release syndrome (CRS), neurologic toxicities and anaphylaxis. Therefore, we developed controllable CART system which allows us to switch on/off the UCART cells inside human body to maximally restrict the potential damages caused by adverse effects as well as off-target. With that, we are able to precisely control the strength of UCART cells in both temporal and dosage to meet the personalized needs.

Adeno-associated virus (AAV) is a widely used single strand DNA virus. Compared with lentivirus, AAV is considered a safer vector for gene therapy and immunotherapy, because it causes mild immune response, lacks pathogenicity, infects both dividing and quiescent cells without integrating into host genome. These features make AAV a more attractive candidate for CART as it significantly reduced the off-target effects and tumorigenesis risk resulting from chromosome interference.

Tumor microenvironment (TME) is an immune inhibitory environment, which is widely considered as key factors that harmers immunotherapy application especially in solid tumor treatment. We have figured out different strategies to counteract the TME to enhance T cells to kill tumor cells. On one hand, we are applying oncolytic viruses in combination with immunotherapy to boost the activity of T cells in proliferation, persistence and potency. On the other hand, immune checkpoint blockage is taken into consideration to synergize the CART treatment.

It has been shown the design and component of costimulation domain determines the T cell proliferation, persistence and clinical response. Currently, typical constimulation domain consists of the T cell receptor CD3ζ chain and one or more signaling domains from CD28, 4-1BB, OX40, CD27 or ICOS costimulatory proteins. We are developing and optimizing novel costimulation domain that could further augment the CART cells function, safety and clinical effects.

It has been widely accepted that immune cell therapy functions by directing T cells against target molecules expressed selectively on tumor cells, thus novel scFv discovery is critical for expanding the realm of immunotherapy. We have built a multidisciplinary platform for high throughput target screening and scFv verification for more effective immunotherapy development.

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