Publications by authors named "Melissa Ramones"
Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR.
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- CD22 serves as an alternative target for immunotherapy in B cell acute lymphoblastic leukemia (ALL), especially after patients relapse from CD19-directed CAR T cell treatments.
- In two pilot clinical trials (NCT02588456 and NCT02650414), researchers evaluated a CD22-targeting CAR T cell using a 4-1BB-based design, focusing on safety and antileukemic efficacy, but found unexpectedly low response rates.
- Further investigation revealed that modifying the CAR's linker led to improved receptor function through autonomous signaling, suggesting that this signaling enhances CAR T cell efficacy and informing the development of a new CAR construct for clinical testing.
Target-mediated toxicity is a major limitation in the development of chimeric antigen T-cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues that express it at physiologic levels. A CAR-expressing T-cell panel was generated with target antigen affinities varying over three orders of magnitude.
View Article and Find Full Text PDFChimeric antigen receptors (CARs) are synthetic molecules designed to redirect T cells to specific antigens. CAR-modified T cells can mediate long-term durable remissions in B cell malignancies, but expanding this platform to solid tumors requires the discovery of surface targets with limited expression in normal tissues. The variant III mutation of the epidermal growth factor receptor (EGFRvIII) results from an in-frame deletion of a portion of the extracellular domain, creating a neoepitope.
View Article and Find Full Text PDFR-spondin proteins sensitize cells to Wnt signalling and act as potent stem cell growth factors. Various membrane proteins have been proposed as potential receptors of R-spondin, including LGR4/5, membrane E3 ubiquitin ligases ZNRF3/RNF43 and several others proteins. Here, we show that R-spondin interacts with ZNRF3/RNF43 and LGR4 through distinct motifs.
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