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Zusammenfassung Mehr als 90% der an Colisepsis gestorbenen Kalber sind agammaglobulinaemisch, obwohl sie am ersten Lebenstag Colostrum erhielten. Der Mechanismus des vermuteten Resorptionsblocks im Dunndarm ist noch nicht klar. Eine Blockierung durch vorausgegangene Eiweisaufnahme, wie sie von Payne und Marsh postuliert wurde, konnte von uns mit Lissamin-Rhodamin-markiertem Colostrumserum vorlaufig nicht bestatigt werden. Zur Prophylaxe geben wir 100 ml Colostrumserum intravenos so bald als moglich nach der Geburt. Damit konnte bei 14 Versuchskalbern eine experimentelle Colisepsis verhindert werden, wahrend 10 Kontrolltiere ohne Injektion von Gammaglobulin die nasal gesetzte Coliinjektion nicht uberlebten. Die Frage der Gammaglobulinprophylaxe, auch in der Humanmedizin, wird diskutiert. Sie verspricht gute Erfolge in der Verhutung von Kalberverlusten. Summary Pathogenesis and prophylaxis of coliform infections in calves More than 90% of calves dying from E. coli septicaemia are agammaglobulinaemic although they receive colostrum in the first days after birth. The mechanism of the presumed absorption block in the duodenum is not yet clear. Blockage provoked by previous ingestion of proteins, as was postulated by Payne and Marsh, could not be confirmed by using colostrum-serum marked with Lissamine-Rhodamine. For prophylaxis the authors give 100 ml. of colostrum-serum intravenously as soon as possible after birth. By this method 14 calves were protected from experimental coli septicaemia, whereas 10 uninjected controls failed to survive the intranasal inoculation of E. coli. Gamma globulin prophylaxis in human medicine is discussed and good results are reported in preventing losses in calves but not as a form of treatment. Resume Formation et empechement de la coli-infection des veaux Plus de 90% des veaux morts d'une septicemic colibacillaire, sont agammaglobulinemiques, bien qu'ils aient recu le jour de leur naissance du colostrum. Le mechanisme du bloc de resorption de l'intestin grele n'est pas encore clair. Un blocage provoque par une precedante consommation de proteines comme l'avaient postulee Payne et Marsh n'a pas pu etre confirmee en ce moment avec du serum de colostrum marque par nous de Lissamin-Rhodamin. Apres la naissance nous donnons aussi vite que possible 100 ml de serum de colostrum par voie intraveineuse comme prophylaxie. Ainsi une septicemie colibacillaire experimentale a pu etre empechee chez 14 veaux d'essai, tandis que 10 animaux de controle sans l'injection de gammaglobuline n'ont pas survecu a l'injection colibacillaire nasale. La question de la prophylaxie avec de la gammaglobuline dans la medicine humaine est discutee. Elle promet des resultats egales dans la prophylaxie de pertes de veaux. Resumen Patogenia y profilaxis de la coliinfeccion de los terneros Mas del 90% de los terneros muertos por colisepsis son agammaglobulinemicos, aunque recibieran calostro el primer dia de vida. Todavia no se ha aclarado el bloqueo de resorcion sospechado en el intestino delgado. El bloqueo mediante absorcion proteica anterior, tal y como fue postulado por Payne y Marsh, no pudo confirmarse de antemano por nosotros con el suero calostral marcado con lissamina-rhodamina. En calidad de profilaxis, administramos por via intravenosa 100 ml de suero calostral tan pronto resulta posible despues del parto. De esta forma se pudo impedir en 14 terneros de ensayo una colisepsis experimental, mientras que 10 animales de control sin inyeccion globulinica gamma no sobrevivieron la coliinyeccion facilitada por via nasal. Se discute la cuestion de la profilaxis gammaglobulinica, incluso desde el aspecto de la medicina humana. Promete resultados superiores en la evitacion de perdidas entre los terneros.

We recently reported that triplebody 19-3-19 can engage and activate T cells as cytolytic effectors via a central OKT3-derived single chain variable fragment (scFv) domain (Roskopf et al., 2014). Antibody-derivatives in the triplebody format can simultaneously target two different tumour cell antigens (“dual-targeting”), while concomitantly recruiting immune effector cells. To take full advantage of this dual-targeting capacity, a triplebody 33-3-19, designed for lysis of CD19+ CD33+ biphenotypic leukaemia cells with enhanced selectivity, was also constructed and analysed. 33-3-19 was produced in suspension-adapted 293F cells, purified and tested using standard molecular biology and flow cytometric techniques. 33-3-19 activated T cells as efficiently as 19-3-19 and induced the specific lysis of established myeloid (MOLM13, THP-1) as well as B cell lines (SEM, Raji) and of primary patient cells at picomolar concentrations. However, 33-3-19 achieved a lower maximal specific lysis of the B lymphoid cell lines (35–55 %) than 19-3-19 (55–90 %) in 3 h. This may in part be due to its monovalent affinity for CD19. Importantly, 33-3-19 induced the preferential lysis of double- over single-positive leukaemia cells (i.e. BV173 versus SEM cells) in a target cell mixture. Finally, 33-3-19 led to the elimination of >95% colony-forming leukaemia-initiating cells. These results highlight the potential of dual-targeting triplebodies for efficient and selective immune-intervention.