Intraoperative blood salvage (IBS) reduces exposure to allogeneic blood but is accompanied by concerns in oncologic surgery regarding the potential reinfusion of residual tumor cells and subsequent metastatic dissemination. The CATUVAB® procedure was developed to eliminate EpCAM-positive tumor cells from autologous erythrocyte concentrates (EC). As CATUVAB® requires integration of a leukocyte depletion filter (LDF), the present study aimed to evaluate whether three different commercially available LDF meet predefined safety and efficacy criteria within this procedure. In this prospective ex vivo study, intraoperatively collected blood from patients undergoing major oncologic surgery was processed using the CATUVAB® procedure in combination with one of three LDF (Fresenius BioR Flex AT, Haemonetics US RS1, Puriblood LRW-50–04-PS). The primary endpoint was depletion of EpCAM-positive tumor cells. Secondary endpoints included residual catumaxomab levels in the final EC and changes in proinflammatory cytokines (IL-6, IL-8, TNF-α, IFN-γ). Removal of EpCAM/CD133 double-positive cancer stem cells was explored in a subgroup. Thirty-one patients were analyzed. EpCAM-positive tumor cells were detected in intraoperative blood in a substantial proportion of samples, with marked interindividual variability in tumor cell burden. After CATUVAB® processing and final filtration, no EpCAM-positive tumor cells were detectable in any EC, irrespective of the LDF used. EpCAM/CD133 double-positive cancer stem cells were also eliminated in the subgroup. Residual catumaxomab was detectable in a proportion of ECs but consistently remained below the predefined safety threshold of 70 ng per EC. IL-6 and IL-8 levels were markedly reduced during processing across all filter types, whereas tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ) were largely below detection limits. The present study demonstrates that the CATUVAB® procedure, in combination with different leukocyte depletion filters, achieved effective removal of EpCAM-positive tumor cells, accompanied by low residual catumaxomab levels and reduced pro-inflammatory cytokine concentrations. These findings support the feasibility of this approach; however, given the limited sample size and exploratory design, they should be considered preliminary and require confirmation in larger studies.

Transurethral resection of the tumor (TUR-B) followed by adjuvant intravesical treatment with cytostatic drugs or Bacillus Calmette–Guérin (BCG) as standard therapy of non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence rate of about 60–70%, considerable side effects and requires close monitoring. Alternative treatment options are warranted. Two patients with epithelial cell adhesion molecule (EpCAM)-positive recurrent non-muscle invasive bladder cancer were treated the first time by an intravesical administration of the trifunctional bispecific EpCAM targeting antibody catumaxomab (total dosage of 470 and 1120 µg, respectively). The binding and killing activity of catumaxomab in urine milieu was evaluated in vitro. In contrast to its previous systemic application catumaxomab was well tolerated without any obvious signs of toxicity. Relevant cytokine plasma levels were not detected and no significant systemic drug release was observed. The induction of a human anti-mouse-antibody (HAMA) reaction was either absent or untypically weak contrary to the high immunogenicity of intraperitoneal applied catumaxomab. Tumor cells that were detectable in urine patient samples disappeared after catumaxomab therapy. Endoscopically confirmed recurrence-free intervals were 32 and 25 months. Our data suggest that intravesical administration of catumaxomab in NMIBC is feasible, safe and efficacious, thus arguing for further clinical development of catumaxomab in this indication.

Background Intraoperative blood salvage (IBS) is regarded as an alternative to allogeneic blood transfusion excluding the risks associated with allogeneic blood. Currently, IBS is generally avoided in tumor surgeries due to concern for potential metastasis caused by residual tumor cells in the erythrocyte concentrate. Methods The feasibility, efficacy and safety aspects of the new developed Catuvab procedure using the bispecific trifunctional antibody Catumaxomab was investigated in an ex-vivo pilot study in order to remove residual EpCAM positive tumor cells from the autologous erythrocyte concentrates (EC) from various cancer patients, generated by a IBS device. Results Tumor cells in intraoperative blood were detected in 10 of 16 patient samples in the range of 69–2.6 × 10 5 but no residual malignant cells in the final erythrocyte concentrates after Catuvab procedure. IL-6 and IL-8 as pro-inflammatory cytokines released during surgery, were lowered in mean 28-fold and 52-fold during the Catuvab procedure, respectively, whereas Catumaxomab antibody was detected in 8 of 16 of the final EC products at a considerable decreased and uncritical residual amount (37 ng in mean). Conclusion The preliminary study results indicate efficacy and feasibility of the new medical device Catuvab allowing potentially the reinfusion of autologous erythrocyte concentrates (EC) produced by IBS device during oncological high blood loss surgery. An open-label, multicenter clinical study on the removal of EpCAM-positive tumor cells from blood collected during tumor surgery using the Catuvab device is initiated to validate these encouraging results.