@article{RitterZimmermannJoehrensetal.2018,
  author    = {Ritter, Julia and Zimmermann, Karin and J{\"o}hrens, Korinna and Mende, Stefanie and Seegebarth, Anke and Siegmund, Britta and Hennig, Steffen and Todorova, Kremena and Rosenwald, Andreas and Daum, Severin and Hummel, Michael and Schumann, Michael},
  title     = {T-cell repertoires in refractory coeliac disease},
  series = {Gut},
  volume    = {67},
  journal   = {Gut},
  number    = {4},
  doi       = {10.1136/gutjnl-2016-311816},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226350},
  pages     = {644-653},
  year      = {2018},
  abstract  = {Objective Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. Design DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n= 8), RCD type II (n= 8) and unclassified Marsh I cases (n= 3) collected from 2002 to 2013 was examined by TCR beta-complementarity- determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. Results On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCR beta rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6\% of all TCR beta rearrangements, which was significantly higher than in controls (6.8\%; p<0.01) or RCD type I (6.7\%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliad-independent CDR3 motifs were only detectable at low frequencies. Conclusions TCR beta-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCR beta rearrangements. Dominant TCR beta sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.},
  language  = {en}
}
@article{KnoedlerKoerferKunzmannetal.2018,
  author    = {Kn{\"o}dler, Maren and K{\"o}rfer, Justus and Kunzmann, Volker and Trojan, J{\"o}rg and Daum, Severin and Schenk, Michael and Kullmann, Frank and Schroll, Sebastian and Behringer, Dirk and Stahl, Michael and Al-Batran, Salah-Eddin and Hacker, Ulrich and Ibach, Stefan and Lindhofer, Horst and Lordick, Florian},
  title     = {Randomised phase II trial to investigate catumaxomab (anti-EpCAM × anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer},
  series = {British Journal of Cancer},
  volume    = {119},
  journal   = {British Journal of Cancer},
  doi       = {10.1038/s41416-018-0150-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325938},
  pages     = {296-302},
  year      = {2018},
  abstract  = {Background Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC. Methods This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery. Results Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27\% in arm A and 19\% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms. Conclusions Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.},
  language  = {en}
}