Bacteria and Virus Use For Cancer Treatment
By nature, bacteria and viruses have a self-amplifying property and can be tumour-selective, stimulating the immune system to kill the cancer cells. According to Dr Ramon Alemany of the Catalan Institute of Oncology in Barcelona, these properties make bacteria and viruses great anti-cancer agents.
In 1890, William Coley introduced a strain of Streptococcus in 10 cancer patients. The trial produced one successful result. 40 years later, over 1000 patients with bone and soft tissue sarcomas improved tremendously after injections with Coley’s toxins.
The testing of interferon-sensitive viruses – that is currently under development today – began in the 1950s. Recent studies have modified viruses and bacteria to less virulent but tumour selective cells. They are modified by targeting, arming, and shielding. Targeting differentiates the cells into the specific tumour cells; arming occurs through the presence of proteins convertase and cytokines to activate the formed inactive agents; and coating with polymers and envelops provides shielding from immune response.
Talimogene laherpareve (T-VEC) was the first viral anti-cancer agent to be approved for the treatment of skin and lymph node lesions that could not be surgically removed. In a clinical trial for patients with stage 3 melanoma, the response rate was 33% for injected tumours, 16% for skin metastases, and 3% for visceral metastases.
Dr Alemany cited systemic delivery, the viral spread within the tumour, and improving anti-tumour versus anti-virus immune response as some of the greatest challenges faced by virotherapy. As solution to these challenges, some strategies could be applied: using albumin to mask the virus and arming the viruses with hyaluronidase.
Melanoma patients show better responses to oncolytic viruses when combined with checkpoint inhibitors. According to Dr Alemany, combining the anti-cancer viruses with antitumour, bispecific T-cell engagers, or tumour epitopes are possible therapeutic strategies.
Ongoing clinical trials are investigating obligate and facultative anaerobes for use in cancer treatment. Obligate anaerobes grow in the centre of the tumour and include Clostridium, Lactobacillus and Bifidobacterium. Facultative anaerobes, such as Listeria, Shigella, Salmonella, and Escherichia, grow in the more oxygenated parts of tumours.
“Listeria has been used in several different clinical trials,” said Dr Alemany. He is hopefully that in the future scientists will be using “bacteria and viruses with better tumour-targeting intra-tumoural spread and improved properties to elicit anti-tumour immunity.”
According to Dr Tassone of the Tommasso Campanella Cancer Centre in Italy, RNAs do not need to be intra-tumoural to be functional; they produce longer-lasting responses and are well tolerated. The use of RNA therapeutics is quite simple and he is hopeful about its future in cancer treatment.
Recent studies show that RNAs contribute in the formation of tumours, controlling their progression, and conferring drug resistance.
The first cancer-targeted miRNA drug is currently under clinical trials in cancer patients; and phase 2 is planned. Other RNA therapeutics are also under trial for cancer treatment.
Scientists are optimistic about the success of oncolytic viral therapy, bacterial-based therapies and RNA therapeutics for the cancer treatment.