SUMMARY A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes — infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy.

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SummaryTime series gene expression (transcriptome) data provide information on global changes in expression patterns occurring through the course of cancer progression. The premise of this work is that cancer can be viewed as a state transition of the transcriptome, and that the transcriptome behaves as a particle in a force field obeying basic physical principles of motion.The implication of this concept is that cancer progression may be understood, and predicted, with mathematical models of motion of the transcriptome in a low-dimensional projection that can be constructed to retain a maximal amount of relevant information in the system. We use a genetic mouse model of acute myeloid leukemia (AML) to demonstrate the concepts of our mathematical model. We show that the transition of the transcriptome from a health state to a leukemia state can be understood in terms of mathematically-derived inflection points which characterize the dynamic probability of leukemia development.