Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML.

Although the landscape for treating acute myeloid leukemia (AML) patients has changed substantially in recent years, the majority of patients will eventually relapse and succumb to their disease. Allogeneic stem cell transplantation provides the best anti-AML treatment strategy, but is only suitable in a minority of patients. In contrast to B-cell neoplasias, chimeric antigen receptor (CAR) T-cell therapy in AML has encountered challenges in target antigen heterogeneity, safety, and T-cell dysfunction. We established a Fab-based adapter CAR (AdCAR) T-cell platform with flexibility of targeting and control of AdCAR T-cell activation. Utilizing AML cell lines and a long-term culture assay for primary AML cells, we were able to demonstrate AML-specific cytotoxicity using anti-CD33, anti-CD123, and anti-CLL1 adapter molecules in vitro and in vivo. Notably, we show for the first time the feasibility of sequential application of adapter molecules of different specificity in primary AML co-cultures. Importantly, using the AML platform, we were able to demonstrate that chronic T-cell stimulation and exhaustion can be counteracted through introduction of treatment-free intervals. As T-cell exhaustion and target antigen heterogeneity are well-known causes of resistance, the AdCAR platform might offer effective strategies to ameliorate these limitations.

[The value of computed tomography in the diagnosis of the local and lymph node recurrences of head and neck tumors]. / Wertigkeit der Computertomographie bei der Diagnose von Lokal- und Lymphknotenrezidiven von Kopf-Hals-Tumoren.

544 CT studies of 231 patients were evaluated retrospectively to assess the role of CT in posttherapeutic monitoring of patients with head and neck tumours. CT (80%) was inferior to clinical evaluation (87%) in diagnosing recurrent malignancy due to a lack of specificity (76 vs. 92%). With CT small recurrencies were missed. Occasionally evaluation of the oral cavity was impaired by metal artifacts (dental fillings). However with larger recurrent tumours, CT offered important additional information regarding extent, infiltration of deeper compartments and bony destruction in 51% of the cases. CT (95%) was superior to clinical evaluation (80%) in diagnosing recurrent lymph node metastases. A baseline CT study at about 6-8 weeks after the end of therapy is of great importance for follow-up studies.

Preliminary results with the clonidine suppression test in the diagnosis of pheochromocytoma.

23 patients presenting with symptoms of pheochromocytoma were subjected to the clonidine suppression test. In 6 patients, in whom a pheochromocytoma was surgically approved later on, norepinephrine was not suppressed by clonidine. 17 patients in whom a secondary form of hypertension could be excluded by other diagnostic measures showed a marked decrease of plasma norepinephrine. Apart from drowsiness, no adverse side effects were observed. In our hands, the clonidine test proved as a safe and specific test in the diagnosis of pheochromocytoma.