Publications by authors named "Andrea Garmilla"
Article Synopsis
- Tumor-infiltrating-lymphocyte (TIL) therapy can leverage the body's own T cells to fight tumors but has lengthy production processes that may reduce effectiveness.
- Researchers introduced a method using retroviral vectors paired with peptide-major histocompatibility complexes (pMHC) to deliver genes specifically to CD8 T cells, aiming to enhance their anti-tumor functions.
- The study showed that these pMHC-targeted viral vectors succeeded in activating and expanding effective anti-tumor T cells in mice, potentially simplifying the production of engineered cell therapies and improving survival rates in tumor-bearing models.
Chimeric antigen receptor therapies have demonstrated potent efficacy in treating B cell malignancies, but have yet to meaningfully translate to solid tumors. Here, we utilize our pooled screening platform, CARPOOL, to expedite the discovery of CARs with anti-tumor functions necessary for solid tumor efficacy. We performed selections in primary human T cells expressing a library of 1.
View Article and Find Full Text PDFThe anti-tumor function of engineered T cells expressing chimeric antigen receptors (CARs) is dependent on signals transduced through intracellular signaling domains (ICDs). Different ICDs are known to drive distinct phenotypes, but systematic investigations into how ICD architectures direct T cell function-particularly at the molecular level-are lacking. Here, we use single-cell sequencing to map diverse signaling inputs to transcriptional outputs, focusing on a defined library of clinically relevant ICD architectures.
View Article and Find Full Text PDFThe efficacy of adoptive T-cell therapies largely depends on the generation of T-cell populations that provide rapid effector function and long-term protective immunity. Yet it is becoming clearer that the phenotypes and functions of T cells are inherently linked to their localization in tissues. Here we show that functionally distinct T-cell populations can be generated from T cells that received the same stimulation by altering the viscoelasticity of their surrounding extracellular matrix (ECM).
View Article and Find Full Text PDFOncogenesis often implicates epigenetic alterations, including derepression of transposable elements (TEs) and defects in alternative splicing. Here, we explore the possibility that noncanonical splice junctions between exons and TEs represent a source of tumor-specific antigens. We show that mouse normal tissues and tumor cell lines express wide but distinct ranges of mRNA junctions between exons and TEs, some of which are tumor specific.
View Article and Find Full Text PDFArticle Synopsis
- CD8 T cell responses to different tumor neoantigens happen at the same time, but how they influence each other and overall tumor control is not well understood.
- In a mouse model of lung adenocarcinoma, it was discovered that the most stable binding of an antigen to MHC drives the dominant CD8 T cell expansion, while subdominant T cells show a TCF1 progenitor phenotype linked to immune checkpoint blockade (ICB) therapy responses.
- However, a dysfunctional subset of subdominant TCF1 cells, identified by markers like CCR6 and Tc17 differentiation, limits their benefit from ICB, but using vaccination helps eliminate these cells and enhances the subdominant T cell response against tumors.