2022
DOI: 10.3390/cancers14225485
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T Cells Directed against the Metastatic Driver Chondromodulin-1 in Ewing Sarcoma: Comparative Engineering with CRISPR/Cas9 vs. Retroviral Gene Transfer for Adoptive Transfer

Abstract: Ewing sarcoma (EwS) is a highly malignant sarcoma of bone and soft tissue with early metastatic spread and an age peak in early puberty. The prognosis in advanced stages is still dismal, and the long-term effects of established therapies are severe. Efficacious targeted therapies are urgently needed. Our previous work has provided preliminary safety and efficacy data utilizing T cell receptor (TCR) transgenic T cells, generated by retroviral gene transfer, targeting HLA-restricted peptides on the tumor cell de… Show more

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“…Recent work from Schober et al demonstrated that orthotopic TCR replacement using nonviral methods results in near-physiological T-cell function [ 212 ], thereby preventing potential mispairing of endogenous and extraneous TCR. Our work also provides evidence that CRISPR/Cas9-engineered TCR replacement by TCR targeting CHM1 in T-cells could enhance the longevity of the cytotoxic effect of targeting EwS compared with the transgenic T-cells via retrovirus [ 213 ]. Metabolic or epigenetic reprogramming to enhance the function of T-cells provides another therapeutic option [ 214 ].…”
Section: Perspectivesmentioning
confidence: 99%
“…Recent work from Schober et al demonstrated that orthotopic TCR replacement using nonviral methods results in near-physiological T-cell function [ 212 ], thereby preventing potential mispairing of endogenous and extraneous TCR. Our work also provides evidence that CRISPR/Cas9-engineered TCR replacement by TCR targeting CHM1 in T-cells could enhance the longevity of the cytotoxic effect of targeting EwS compared with the transgenic T-cells via retrovirus [ 213 ]. Metabolic or epigenetic reprogramming to enhance the function of T-cells provides another therapeutic option [ 214 ].…”
Section: Perspectivesmentioning
confidence: 99%