Publications by authors named "B Basagoiti Carreno"
Article Synopsis
- - The study investigates T cell responses to KRAS mutations, particularly the KRASG12V variant, and focuses on T cell receptors (TCRs) that are specific to this mutation within certain HLA class I alleles.
- - It reports on a clinical vaccine trial that successfully primed both CD8+ and CD4+ T cell responses against KRASG12V, revealing that natural TCRs showed high specificity and effectiveness in targeting mutated cancer cells without affecting normal cells.
- - The findings suggest a strong therapeutic potential for these KRASG12V-specific TCRs in developing targeted T cell therapies, highlighting their ability to effectively attack tumors even with low levels of antigen presentation.
Article Synopsis
- Many patients treated with FDA-approved CAR T cells see their disease progress, especially with solid cancers and certain types of blood cancers like T cell lymphomas.
- A major challenge in adoptive T cell therapies is the dysfunction of CAR T cells, which struggle to expand and last after being infused.
- The study reveals that knocking out the CD5 gene using CRISPR-Cas9 can improve the antitumor abilities of CAR T cells by enhancing their function and persistence, suggesting CD5 as a key target for improving T cell therapies.
In this commentary, we advance the notion that mutant KRAS (mKRAS) is an ideal tumor neoantigen that is amenable for targeting by the adaptive immune system. Recent progress highlights key advances on various fronts that validate mKRAS as a molecular target and support further pursuit as an immunological target. Because mKRAS is an intracellular membrane localized protein and not normally expressed on the cell surface, we surmise that proteasome degradation will generate short peptides that bind to HLA class I (HLA-I) molecules in the endoplasmic reticulum for transport through the Golgi for display on the cell surface.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T cell therapy has been successful for hematological malignancies. Still, a lack of efficacy and potential toxicities have slowed its application for other indications. Furthermore, CAR T cells undergo dynamic expansion and contraction in vivo that cannot be easily predicted or controlled.
View Article and Find Full Text PDFDespite the success of CAR-T cell cancer immunotherapy, challenges in efficacy and safety remain. Investigators have begun to enhance CAR-T cells with the expression of accessory molecules to address these challenges. Current systems rely on constitutive transgene expression or multiple viral vectors, resulting in unregulated response and product heterogeneity.
View Article and Find Full Text PDF