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Bacterial-based immunotherapy

It was at the end of the 19th century that bacteria were for the first time intentionally applied for cancer treatment. William Coley, a bone sarcoma surgeon at the Memorial Hospital in New York, having conducted a thorough literature search, found 47 well-documented cases of beneficial influence of serious bacterial infections in tumor patients [1]. He further concocted a mixture of killed Streptococcus pyogenes and Serratia marcescens bacteria, which became known as Coley’s toxin. Over the next forty years Coley applied his toxin to almost 1000 patients who suffered from various types of inoperable cancers. Striving to improve the effectiveness of the therapy, he used various doses of his toxin, different regimens and durations of treatment, as well as different routes of application and therefore it is difficult to fully comprehend his enormous work. 

In many cases several-month treatment resulted in complete tumor regression. The five-year survival period for patients suffering from inoperable carcinomas ranged from 34 to 73%, and for those suffering from inoperable sarcomas was in the range between 13 and 79%, varying with the tumor subtype [2]. With the progress of immunology it became clear that the mechanism of action of Coley’s toxin involves activation of the immune system and a multilevel modulation of immune response. This understanding restored interest in possible therapeutic applicability of Coley’s approach. 

In line with Coley’s concept of using bacteria in cancer therapies, other bacterial species were evaluated for a possible anti-tumor effect. Bacillus Calmette-Guerin (BCG), attenuated bovine tuberculosis bacteria (Mycobacterium bovis), has been used for decades as a vaccine protecting against tuberculosis. 

However, it also appeared to be one of the most successful cancer immunotherapeutics. BCG, in the form of repeated intravesical instillations, has already been in use for over 30 years as a standard method to prevent cancer recurrence after endoscopic surgery of intermediate- and high-risk non-muscle invasive bladder cancer [3]. It is also effective against inoperable bladder carcinoma in situ resulting in a 70–75% complete response rate [4]. Unfortunately, in other tumor types BCG application has not proved to be more effective than conventional therapies [4]. Therefore, other bacteria such as Clostridium, Bifidobacterium, Salmonella were studied to apply in this field [5].

1.EF, M., The toxins of William B Coley and the treatment of bone and soft-tissue sarcomas. . Iowa Orthop J 2006. 26: p. 148-54.

2.Green PN, H.C.S., Bacterial anti-cancer vaccines: a science frozen in time. Microbiologist, 2007. 8: p. 29-34.

3.Kawai K, M.J., Joraku A, Nishiyama H, Akaza H Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: current understanding and perspectives on engineered BCG vaccine. . Cancer Sci 2013. 104: p. 22-27.

4.Alexandroff AB, J.A., O’Donnell MA, James, K  BCG immunotherapy of bladder cancer: 20 years on. . Lancet, 1999. 353(1689-94).

5.Pawelek, J., K. Low, and D. Bermudes, Bacteria as tumour-targeting vectors. Lancet Oncol, 2003. 4: p. 548-556.

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