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Purpose A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR) engineered, autologous primary human CD8+ cytolytic T lymphocytes (CTLs) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). Experimental Design Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8+ CTL targeting IL13Rα2. Patients received up to twelve local infusions at a maximum dose of 108 CAR-engineered T cells via a catheter/reservoir system. Results We demonstrate the feasibility of manufacturing sufficient numbers of autologous CTL clones expressing an IL13(E13Y)-zetakine CAR for redirected HLA-independent IL13Rα2-specific effector function for a cohort of patients diagnosed with GBM. Intracranial delivery of the IL13-zetakine+ CTL clones into the resection cavity of three patients with recurrent disease was well-tolerated, with manageable temporary CNS inflammation. Following infusion of IL13-zetakine+ CTLs, evidence for transient anti-glioma responses was observed in two of the patients. Analysis of tumor tissue from one patient before and after T cell therapy suggested reduced overall IL13Rα2 expression within the tumor following treatment. MRI analysis of another patient indicated an increase in tumor necrotic volume at the site of IL13-zetakine+ T cell administration. Conclusion These findings provide promising first-in-human clinical experience for intracranial administration of IL13Rα2-specific CAR T cells for the treatment of GBM, establishing a foundation on which future refinements of adoptive CAR T cell therapies can be applied.

Inverse source reconstruction is the most challenging aspect of bioluminescence tomography (BLT) because of its ill-posedness. Although many efforts have been devoted to this problem, so far, there is no generally accepted method. Due to the ill-posedness property of the BLT inverse problem, the regularization method plays an important role in the inverse reconstruction. In this paper, six reconstruction algorithms based on l p regularization are surveyed. The effects of the permissible source region, measurement noise, optical properties, tissue specificity and source locations on the performance of the reconstruction algorithms are investigated using a series of single source experiments. In order to further inspect the performance of the reconstruction algorithms, we present the double sources and the in vivo mouse experiments to study their resolution ability and potential for a practical heterogeneous mouse experiment. It is hoped to provide useful guidance on algorithm development and application in the related fields.

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