Bacteriolytic therapy of experimental pancreatic carcinoma

Abstract

The Vogelstein Lab demonstrated in pionier work that spores of Clostridium novyi NT are efficient in eradicating established solid tumors in combination with standard chemotherapy [1]. Despite progress of oncologic and surgical therapy pancreatic cancer still has an outstanding poor prognosis. Therefore, we investigated the effectiveness of attenuated Clostridium novyi spores (C. novyi-NT) for treatment of established subcutaneous Panc02 tumors in the syngeneic, immunocompetent C57BI/6 model. After corresponding growth of tumor c. novyi NT Spores (75 Mio) were applied intravenously. These experiments demonstrated, that (I) small tumors (<100 mm3) were completely unaffected (n=13), (II) very large tumors (>500 mm3) responded with substantial necrosis followed by shrinkage accompanied with disastrous lethality due to tumor lysis syndrome (n=3), (III) an optimal treatment window exists for tumors of approximately 300 mm3 (n=20).In this group 30% (6/20) of tumor bearing animals had a complete tumor regression and remained free of tumor recurrence for an observation period of 14 days. In following tumor rechallenge experiments a significant delay of tumor growth compared to first time tumor cell inoculation was observed (tumorvolume day 18 after rechallenge 12,7±9,8 mm3 vs. 141,5±101,7 mm3; p<0,05).The poor prognosis of advanced pancreatic cancer despite advances in oncologic and surgical therapy emphasizes the need of novel therapeutical stategies. Our encouraging observation of complete tumor regression in 30% of tumor bearing animals shows that active unspecific bacterial immunotherapy with C. novyi-NT spores is a promising new strategy for treatment of advanced pancreatic carcinoma.