Antitumor effect of VPN20009, an attenuated Salmonella, in murine tumor models.

X Luo, Z Li, L Zheng, S Lin, T Le, M Ittensohn… - 2001 - csun-dspace.calstate.edu
X Luo, Z Li, L Zheng, S Lin, T Le, M Ittensohn, D Bermudes, JD Runyab, S Shen, J Chen…
2001csun-dspace.calstate.edu
It has long been known that tumor regression occasion ally occurs in patients with bacterial
infections (1). An infection arising from a tumor may be the first clinical manifestation of
neoplastic disease (2). Numerous clini cal reports describe patients with tumors infected by
bacteria, frequently Salmonella (3-6). For example, Giel (4) described an abscess in a
pheochromocytoma con taining 90 cc of thick, yellow pus encapsulated by a thin sphere
consisting of a few layers of tumor cells. The bacteria were later identified as S. typhimurium …
It has long been known that tumor regression occasion ally occurs in patients with bacterial infections (1). An infection arising from a tumor may be the first clinical manifestation of neoplastic disease (2). Numerous clini cal reports describe patients with tumors infected by bacteria, frequently Salmonella (3-6). For example, Giel (4) described an abscess in a pheochromocytoma con taining 90 cc of thick, yellow pus encapsulated by a thin sphere consisting of a few layers of tumor cells. The bacteria were later identified as S. typhimurium. The use of bacterial products for cancer treatment dates back to the early 1900s. William B. Coley, who was then a surgeon at Memorial Hospital, now Memo rial Sloan-Kettering Cancer Center, observed that pa· tients with sarcoma responded better after surgery if they developed severe postoperative infections. Coley later developed a regimen containing bacterial cell wall components for the treatment of cancer (7). The grain positive bacterium Clostridiwn was evaluated as an anti· cancer agent in clinical trials in the 1970s. Although in many cases Clostridiwn was recovered from tumors and oncolysis was observed, these clinical trials were subse quently discontinued because they failed to produce clinical benefits to patients (8). Bacille Calmette-Guerin (BCG2), another viable bacterium, is being used for the treatment of superficial bladder carcinoma in h. BCG, an attenuated, avirulent strain of Mycobacterium bovis, is administered by urethral catheterization at peri odic intervals for up to 24 months. In patients with blad der cancer, BCG treannent achieves complete responses in greater than 60% of the patients (9). These reports suggest that bacteria could serve as anticancer agents if their virulence were controlled.
S. typhimurium, if attenuated, can be safely administered to animals to retard tumor growth in murine tumor mod els. A virulent strains of Salmonella have been developed as vaccines for the prevention of bacterial infections (10, 11). A viable S. typhi vaccine, Ty2la, has been ap proved for the prevention of typhoid fever in humans (12). In addition to serving as vaccines against Salmo nellosis, attenuated strains of Salmonella have been used for expressing and delivering heterologous proteins to the immune system. This approach may eventually be developed for combating infections and cancer (13, 14). Using an aro4-mutant SL3225, Eisenstein et al.(14) re ported tumor inhibition of a plasmacytoma by either in traperitoneal or inttalesional injection of the attenuated bacteria. Similar results have been obtained by Pawelek et al.(15) using other auxotrophic mutants of S. typhi
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