Clostridial oncolysis in man

Carey, Robert W.; Holland, James F.; Whang, H. Y.; Neter, Erwin; Bryant, Ben L.

doi:10.1016/0014-2964(67)90060-6

Cited by 98 publications

(80 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 In the 1960s, anaerobic bacteria were shown to target tumours and replicate within the hypoxic and necrotic regions of these tumours. Clostridium was shown to be effective in causing tumour regression in rodent models, 2-4 but a subsequent clinical trial failed to demonstrate any benefit 5 that would outweigh toxicity. More recently, this concept has been re-evaluated using attenuated strains of Salmonella 6,7 and Clostridium.…”

Section: Introductionmentioning

confidence: 99%

Potential therapeutic applications of recombinant, invasive E. coli

et al. 2004

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Potential therapeutic applications of recombinant, invasive E. coli

et al. 2004

View full text Add to dashboard Cite

“…And indeed, over the past 50 years, several strains of facultative and obligate anaerobic bacteria have been shown to localize and cause lysis in transplanted tumors in animals ( Table 1). These initial animal studies were so encouraging that clinical trials using Clostridium began in the 1960s (8). Unfortunately, the results were not as impressive as anticipated and the trials were discontinued.…”

mentioning

confidence: 96%

Can engineered bacteria help control cancer?

Jain

Forbes

2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…[1][2][3][4] In the medical literature, spontaneous infection of human tumors has been reported. [5][6][7][8][9][10][11][12][13] Based on these findings, a small number of advanced cancer patients were treated systemically (or by direct tumor injection) with non-toxinproducing strains of Clostridia in the 1960s, but this approach was abandoned due to excessive toxicity and minimal antitumor effect.…”

mentioning

confidence: 99%

Pilot trial of genetically modified, attenuated Salmonella expressing the E. coli cytosine deaminase gene in refractory cancer patients

et al. 2003

View full text Add to dashboard Cite

We performed a pilot trial in refractory cancer patients to investigate the feasibility of intratumoral injection of TAPET-CD, an attenuated Salmonella bacterium expressing the E. coli cytosine deaminase gene. A total of three patients received three dose levels of TAPET-CD (3 Â 10 6 -3 Â 10 7 CFU/m 2 ) via intratumoral injection once every 28 days as long as progression of disease or intolerable toxicity was not observed. From days 4 to 14 of each 28 day cycle, patients also received 5-fluorocytosine (5-FC) at a dose of 100 mg/kg/day p.o. divided three times daily. Six cycles of treatment were administered. No significant adverse events clearly attributable to TAPET-CD were demonstrated. Two patients had intratumor evidence of bacterial colonization with TAPET-CD, which persisted for at least 15 days after initial injection. Conversion of 5-FC to 5-fluorouracil (5-FU) as a result of cytosine deaminase expression was demonstrated in these two patients. The tumor to plasma ratio of 5-FU for these two colonized patients was 3.0, demonstrating significantly increased levels of 5-FU at the site of TAPET-CD colonization and insignificant systemic spread of the bacteria. In contrast, the tumor to plasma ratio of 5-FU of the patient who did not show colonization of TAPET-CD was less than 1.0. These results support the principle that a Salmonella bacterium can be utilized as a delivery vehicle of the cytosine deaminase gene to malignant tissue and that the delivered gene is functional (i.e. able to convert 5-FC to 5-FU) at doses at or below 3 Â 10 7 CFU/m 2 .

show abstract

Clostridial oncolysis in man

Cited by 98 publications

References 5 publications

Potential therapeutic applications of recombinant, invasive E. coli

Potential therapeutic applications of recombinant, invasive E. coli

Can engineered bacteria help control cancer?

Pilot trial of genetically modified, attenuated Salmonella expressing the E. coli cytosine deaminase gene in refractory cancer patients

Contact Info

Product

Resources

About