In addition, CD64 was described as an attractive target molecule for bsAb based immunotherapy of cancer [29];
anti-EpCAM × anti-CD64 bsAb were characterized to mediate strong cytotoxicity in vitro after GCSF and IFN-γ pre-stimulation of PBMC [30]. Moreover, two studies using the bsAb MDX-H210 (anti-HER2/neu × anti CD64) demonstrated clinical feasibility but limited clinical efficacy in several patients with a dosage 15 mg/m2 after GCSF or GMCSF stimulation [31, 32]. In this context, it should be highlighted that trAb significantly differ from all described bsAb constructs. TrAb consist of the two potent subclasses mouse IgG2a and rat IgG2b, which determine the Tozasertib supplier unique effector functions. In contrast to similar T-cell redirecting bsAb, this mechanism does not depend on the addition of exogenous cytokines or co-stimulation to provide full anti-tumor activity Birinapant research buy [14] as the formation of a postulated tri-cell complex between tumor cell, T-cell and accessory cell represents a fully self-supporting system for efficient immune cell activation GSK1210151A in vitro [13]. PC is generally seen as terminal tumor stage with rapid progression. Regarding the natural history of PC, where exponential tumor growth is expected, the observed clinical course with stable disease or partial tumor regression in five patients
and the observed mean survival of 11.8 months (median 8.0 months) after trAb therapy is remarkable. None of the nine patients developed accumulation of malignant ascites during therapy, which would have been expected in 20 to 30% of patients
with PC. Although outcome is not the goal of this trial, compared to a mean survival of 6 months (median 3.1 months) from the landmark study by Sadeghi et al. in 370 patients with PC [1] our results are promising. In summary, our results demonstrate that trAb are capable to induce specific tumor immunity against autologous tumor cells. In addition to the well documented ability of tumor cell destruction [21], especially this unique self-supporting efficacy of trAb may provide a new concept in the treatment of intraabdominal tumors. Ongoing studies in early stages of PC and in the patients with high risk for development of peritoneal tumor disease will further evaluate the therapeutic impact of trAb. References 1. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, et al.: Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 2000, 88: 358–363.CrossRefPubMed 2. Gretschel S, Siegel R, Estevez-Schwarz L, Hunerbein M, Schneider U, Schlag PM: Surgical strategies for gastric cancer with synchronous peritoneal carcinomatosis. Br J Surg 2006, 93: 1530–1535.CrossRefPubMed 3. Brenner DE: Intraperitoneal chemotherapy: a review. J Clin Oncol 1986, 4: 1135–1147.PubMed 4. Pilati P, Rossi CR, Mocellin S, Foletto M, Scagnet B, Pasetto L, et al.
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