GO Lab group

Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and function of adoptively transferred CAR T cells can be potentiated by the lymphodepletive and tumoricidal effects of standard of care chemotherapy and radiotherapy. We describe a method for generating CAR T cells targeting EGFRvIII, a glioma-specific antigen, and evaluating their efficacy when combined with a murine model of glioblastoma standard of care...

Unleashing the immune system to fight cancer has become one of the main treatment modalities since the anti-CTLA-4 antibody, ipilimumab was approved for patients with advanced melanoma in 2011. Pembrolizumab and nivolumab, two anti-PD-1 antibodies recently approved for the treatment of patients with metastatic melanoma, are being actively investigated for the treatment of multiple caners including lung, breast, bladder and renal cancers along with other anti-PD-1/L1 antibodies. Early results of combining of anti-CTLA-4 antibody and anti-PD-1 antibody treatment for advanced melanoma patients are showing impressive response rates with manageable toxicity profiles...

Glioblastoma is a highly-aggressive and rapidly-lethal tumor characterized by resistance to therapy. Although data on multiple genes, proteins, and pathways are available, the key challenge is deciphering this information and identifying central molecular targets. Therapeutically targeting individual molecules is often unsuccessful due to the presence of compensatory and redundant pathways, and crosstalk. A systems biology approach that involves a hierarchical gene group networks analysis can delineate the coherent functions of different disease mediators...

This study compared second-generation chimeric antigen receptors (CAR) encoding signaling domains composed of CD28, ICOS, and 4-1BB (TNFRSF9). Here, we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T cells with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to 3 months following a single stimulation through the T-cell receptor (TCR). Sustained numeric expansion was independent of cognate antigen and did not require the addition of exogenous cytokines or feeder cells after a single stimulation of the TCR and CD28...

The adoptive transfer of T cells engineered to express artificial chimeric antigen receptors CARs) that target a tumor cell surface molecule has emerged as an exciting new approach for cancer immunotherapy. Clinical trials in patients with advanced B cell malignancies treated with CD19-specific CAR-modified T cells (CAR-T) have shown impressive antitumor efficacy, leading to optimism that this approach will be useful for treating common solid tumors. Because CAR-T cells recognize tumor cells independent of their expression of human leukocyte antigen (HLA) molecules, tumors that escape conventional T cells by downregulating HLA and/or mutating components of the antigen processing machinery can be eliminated...

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes...