Genetic Engineering Publications - GEG Tech top picks
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Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity - Cell

Vaccine boosting modifies CAR T cell metabolism and promotes crosstalk between CAR
T cells and endogenous immunity to elicit and sustain antigen spreading, thereby effectively
treating tumors with antigen heterogeneity.
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Engineering T cells to destroy cancer cells has proved effective in treating certain types of cancer. However, it has not worked as well for solid tumors. One of the reasons for this lack of success is that T cells only target a single antigen. If some of the tumor cells don't express this antigen, they can evade T cell attack. In 2019, researchers found a way to overcome this obstacle, using a vaccine that enhances CAR-T cell efficacy. In a recent study, researchers wanted to investigate how this additional T-cell response is activated. The researchers discovered that in these vaccinated mice, metabolic changes occur in CAR-T cells that increase their production of interferon gamma, a cytokine that helps stimulate a strong immune response. This helps T cells overcome the tumor's immunosuppressive environment, which normally shuts down all T cells in the vicinity. As CAR-T cells killed tumor cells expressing the target antigen, host T cells encountered other antigens from these tumor cells, stimulating these host T cells to target these antigens and help destroy the tumor cells. Without this host T-cell response, the researchers found that tumors would regrow even if CAR-T cells destroyed most of them. 

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IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas | Genetic Engineering Publications - GEG Tech top picks | Scoop.it
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The authors report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner.These data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.


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