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Adoptive transfer of antigen-specific T cells has recently shown therapeutic successes in the treatment of viral infections and tumors. T cells specific for the antigen of interest can be generated in vitro, and adoptively transferred back to provide patients with large numbers of immune-competent T cells. Adoptive T cell therapy, however, is a patient-tailored treatment that unfortunately is not universally applicable to treat viral infections and tumors. We and others have demonstrated that the transfer of genes encoding antigen-specific receptors into T cells (i.e., genetic retargeting) represents an attractive alternative to induce antigen-specific immunity. Currently, we evaluate this concept in a clinical protocol to treat patients with metastatic renal cell cancer (RCC) using autologous RCC-specific gene-modified T lymphocytes.

Background Ovarian cancer refractory to chemotherapy has a very poor prognosis and no standard treatment options. In a phase I–II study patients with recurrent disease restricted to the peritoneal cavity received intraperitoneal (i.p.) immunotherapy with interleukin-2 (IL-2) and autologous T-cells redirected by bispecific monoclonal antibodies (bs-MAb). Methods A bs-MAb with on the one hand specificity for ovarian cancer cells (the folate binding site MOv 18) and for the CD3 activation site on T-lymphocytes on the other, was produced in large quantities. Lymphocytes, obtained from the patient prior to debulking surgery, were cultured ex vivo and preincubated with the bs-Mab OC/TR (Ovarian Cancer-T cell Receptor) before i.p. administration. IL-2 was given i.p. every 12 hours at a dose of 600.000 IU. The first 4 days increasing numbers of T-cells were administered (106–109 cells), on days 7–11 and 28–32, 109 redirected T-cells were administered each day. Evaluation for tumor response was done by laparotomy 6 weeks after i.p. treatment. Results 11 patients entered the protocol; 10 were evaluable for toxicity; 3 had extracavitary progression without signs of i.p. progression, but were not explored. Therefore in 7 patients i.p. tumor response was evaluated by laparotomy: i.p. CRs were observed in 2 patients, in 1 however there was concurrent PD in retroperitoneal lymph nodes; furthermore 2PRs, 1 SD and 2 PDs were observed. Toxicity was mild, limited to grade 2 fever, abdominal discomfort, tenderness, bloating, and grade 1–2 nausea. Conclusions Immunotherapy with T-cells redirected by bs-Mabs in ovarian cancer has therapeutic potential and should be explored further.

The development of Barbus conchonius is described with special attention to the differentiation of the gut. Amine precursor uptake and decarboxylation (APUD)* are present in enteroendocrine cells during development, whereas these processes are lacking in adult specimens. The first APUD cells originate on the fourth day of development in the anterior part of the gut and on the fifth day in the caudal areas. The APUD facility of the cells disappears within 2 days, and after the 6th day APUD cells can no longer be distinguished in the intestinal epithelium. The first APUD cells were observed when four types of enteroendocrine cells were recognized with the electron microscope. These enteroendocrine cells contain granules of different electron densities, and microtubules and cilia can be observed. Some enteroendocrine-like cells are found below the basement membrane of the intestinal epithelium, indicating a possible extra-endodermal origin. APUD cells, except melanoblasts, have not been found migrating from the neural crest in ventral direction. The origin of the enteroendocrine cells of B. conchonius is discussed. * Abbreviations: APUD, amine precursor uptake and decarboxylation; F1F, formalin-induced fluorescence; L-DOPA, L-dihydroxyphenylalanine; 5-HTP, 5-hydroxytryptophan.

The numbers of mast cells and intra-epithelially located globule leucocytes in the gut mucosa of various animal species, including laboratory rodents and ruminants, increase during the intestinal phase of nematode infections (1,2). Both cell types are characterized by metachromatic intracytoplasmatic granules. Although the cellular response is connected with the immune expulsion of worms from the gut, the function of these cells is still unclear.