Genetic perturbation of T cell receptor (TCR) T cells is a promising method to unlock better TCR T cell performance to create more powerful cancer immunotherapies, but understanding the changes to T cell behavior induced by genetic perturbations remains a challenge. Prior studies have evaluated the effect of different genetic modifications with cytokine production and metabolic activity assays. Live-cell imaging is an inexpensive and robust approach to capture TCR T cell responses to cancer.
View Article and Find Full Text PDFHypodiploid acute lymphoblastic leukemia (ALL) is an aggressive blood cancer with a poor prognosis despite intensive chemotherapy or stem cell transplant. Children and adolescents with positive end-of-induction minimal residual disease have an overall survival lower than 30%. However, data regarding therapeutic alternatives for this disease is nearly nonexistent, emphasizing the critical need for new or adjunctive therapies that can improve outcomes.
View Article and Find Full Text PDFThe efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints. Targeted gene editing has the potential to overcome these limitations and enhance T cell therapeutic function. Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions to identify genes that can be targeted to prevent T cell dysfunction.
View Article and Find Full Text PDFWe recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102.
View Article and Find Full Text PDF