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Co-transplantation of hematopoietic stem cells with those engineered to express leukemia-reactive T cell receptors (TCRs) and differentiated ex vivo into precursor T cells (preTs) may reduce the risk of leukemia relapse. Since expression of potentially self-(leukemia-) reactive TCRs will lead to negative selection or provoke autoimmunity upon thymic maturation, we investigated a novel concept whereby TCR expression set under the control of an inducible promoter would allow timely controlled TCR expression. After in vivo maturation and gene induction, preTs developed potent anti-leukemia effects. Engineered preTs provided protection even after repeated leukemia challenges by giving rise to effector and central memory cells. Importantly, adoptive transfer of TCR-transduced allogeneic preTs mediated anti-leukemia effect without evoking graft-versus-host disease (GVHD). Earlier transgene induction forced CD8+ T cell development, was required to obtain a mature T cell subset of targeted specificity, allowed engineered T cells to efficiently pass positive selection and abrogated the endogenous T cell repertoire. Later induction favored CD4 differentiation and failed to produce a leukemia-reactive population emphasizing the dominant role of positive selection. Taken together, we provide new functional insights for the employment of TCR-engineered precursor cells as a controllable immunotherapeutic modality with significant anti-leukemia activity.

For craniospinal axis irradiation in young children sometimes anesthesia is required. In order to minimize risks from the anesthesist's point of view supine position would be preferable to standard prone position. In case of irradiation in supine position verification of the 3-field junction in the cervical region causes problems, because there is no direct visual control. For such situations the clinical application of a new technique is presented.

Es wird uber eine flammenphotometrische Mikromethode zur Bestimmung von Na, K und Ca berichtet, bei der insgesamt 0,05 cm8 Serum ausreichen, um mit einem Gesamtfehler von ± 1 bis ± 2% Dreifach-Analysen von Na, K und Ca in etwa 1 min gleichzeitig durchzufuhren.

Die fruher von uns beschriebene Mikromethode zur Bestimmung der Serum-Elektrolyte Natrium, Kalium und Calcium wurde an der lebenden Ratten gepruft und ihre Brauchbarkeit zur fortlaufenden Analyse bewiesen.

Wir bestimmten die Serum-Elektrolytwerte Na, K und Ca beim Menschen sowohl aus venosem Blut (Makromethode) als auch gleichzeitig aus Capillarblut (Mikromethode), das der Pingerbeere bzw. dem OhrlAppchen entnommen wurde. Diese Bestimmungen zeigen, da\ die Ca-Konzentrationen mit genugender Genauigkeit aus Capillarblut wiedergegeben werden konnen. Hingegen lassen sich die K- und Na-Werte mit dieser Methode nicht exakt erfassen.