To find better ways to address cancerous tumors that do not respond to traditional therapies, a team of scientists at the Anderson Cancer Center at the University of Texas at Houston (USA) is experimenting with a modified bacterial strain that could target the cancer cells without harming healthy ones. A phase I clinical trial reveals that this bacterial therapy shows promising effects.
The results, so far, suggest that the therapy has manageable toxicity levels and may help shrink some resistant cancer tumors , that is, it would be ideal for patients with few therapeutic options.
What makes bacteria a promising tool
The idea of using bacteria to treat cancer is not new, but until recently, the implementation of bacterial therapies has not been possible due to many obstacles. These include infections and other adverse side effects.
In the new clinical trial, the researchers used spores from a bacterial strain known as Clostridium novyi-NT , which was specifically modified from Clostridium novyi to be used in cancer therapy.
C. novyi-NT has the potential to treat cancer because it thrives in a hypoxic (oxygen-poor) environment, which is precisely the type of environment found in cancerous lesions. Therefore, it can interact with cancer cells without affecting healthy ones.
“By exploiting the inherent differences between healthy and cancerous tissue, C. novyi-NT represents a very precise anticancer therapy that can specifically target a patient’s cancer,” explains Filip Janku, co-author of the work.
The trial was open-label, meaning that all participants knew what type of treatment they were receiving. In total, the researchers worked with 24 participants recruited in 2013-2017. All participants had solid cancer tumors resistant to therapy. Specifically, 15 individuals had sarcoma, 17 diverse carcinoma, and two had melanoma.
The researchers administered C. novyi-NT spore injections directly into the cancerous tumors. They were single doses that contained between 10,000 and 3 million spores of the bacteria.
Two of the people who received the maximum doses of 3 million spores developed severe sepsis and gas gangrene, so the researchers determined that the maximum tolerated dose was 1 million.
They then used RECIST, a test that measures the shrinkage of cancerous tumors in response to treatment, to assess the effect of bacterial therapy. Of the 22 people who met the evaluation criteria, 21 were rated “stable” on the RECIST evaluation, meaning that the disease did not increase or decrease in severity.
In these people the tumors were reduced by more than 10% after the experimental injection.
However, experts note that RECIST tests may not be able to offer a completely accurate understanding of the effectiveness of the bacterial therapy under test.
“When we inject the tumor,” Janku continues, “the cells within it die and become necrotic, while the remaining tissue becomes inflamed, making the lesion larger than the original tumor. Because of this, evaluation through RECIST does not accurately reflect the reduction in tumor burden in these patients. “
Bacterial therapy to boost immunotherapy?
In addition, when they analyzed the germination rates of C. novyi-NT spores, the researchers found that, of the total number of participants, 46% showed spore germination and showed signs of tumor cell disintegration.
However, they also found that bacterial therapy appeared to have boosted the immune system’s response to cancerous tumors.
“From these preliminary results, it appears that C. novyi-NT can activate the immune response in addition to causing tumor destruction ,” they state.
According to the authors, this suggests that bacterial therapy could one day be used to enhance the effects of immunotherapy in treating cancer.
“ We are extremely encouraged by the results of this trial , especially in patients with advanced sarcomas, where immunotherapy has not been shown to be very effective,” says Janku.
Reference: Bacterial therapy tolerable, shows early promise in patients with advanced solid tumors. American Association for Cancer Research 2018 CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, New York City (USA).
