Infecting and Attacking Cancers from within- COBALT

A core issue, with using systemic treatments such as chemotherapy is that they need vessels to reach the tumor site- And hence chemo finds it difficult to reach into the depths of large tumors that have grown so big, that the vessels in the center of the tumor have been squeezed shut.

If the therapeutic drug has no access to the tumorous cells, then it can’t act on them and destroy them.

So how do we address this issue Medically?

Basic Concept

Before getting into that, I’d like you to understand, that at the center-most of the tumor, there’s going to be the least oxygen owing to the lack of O2 carrying blood vessels there.

So, let’s imagine we take an entity that
1.) THRIVES in an environment devoid or deficit in oxygen, and
2.) Is also capable of inducing necrosis, and lysis (destruction) of cells.

In essence, we’d have a material that’d multiply inside the deepest, least oxygenated parts of the tumor and destroy the cells there.

This is where Clostridium novyi comes in.

What is C. novyi?

It is a bacterium with the Exact two features as described above, with one added perk:
C. novyi dies as soon as it is exposed to Oxygen!

What this entails is that C. novyi is capable of destroying the tumor from within, from parts chemo can’t penetrate, but as soon as it reaches the parts at the periphery of the tumor that are oxygenated, it instantly dies.

This limits harm to the normal cells of your body.

Limits of C. novyi

Unfortunately, this also makes it difficult to be used in treatment as a single agent.

For one, we need a very high dose injected intravenously, since by the time the bacteria reach the anaerobic tumor site, most of them die out in our well oxygenated blood.

Secondly, even though the bacterium destroys the tumor from within, there were large recurrences, owing to the fact that a thin rim of cancerous cells got left behind at the oxygenated marginal edge of the tumor.

But that doesn’t mean that C. novyi was to be deemed useless.

Practicalities of C. novyi Therapy

To address the above issues, COBALT was designed. It stands for Combination Bacteriolytic Therapy.

COBALT is based on the rationale that C. novyi destroys the hypoxic and necrotic parts of the tumors, which are traditionally resistant to radiation and cytotoxic agents, while chemotherapies and radiation attack the tumor cells in the proliferating, non-hypoxic areas of the tumor.

Both modalities – chemotherapeutics, particularly microtubule interacting drugs, and various forms of radiation – resulted in synergistic responses when combined with C. novyi with partial or complete regressions in the majority of the various cancer xenograft models.

Dramatic tumor regressions were observed after treatment with C. novyi-NT spores and a microtubule-binding agent, dolastatin-10, or a DNA damaging agent, mitomycin C, in nude mice loading colorectal cancer cell line HCT116.

Furthermore, Clostridium-directed antibody therapy is a combination of the oncolytic properties of C. novyi-NT with the target selectivity of antibody therapeutics, in which the bacteria is used as a carrier for antibodies (specific for human hypoxia-inducible factor 1 alpha) targeting the most resistant regions in human solid cancer.

Today, C. novyi-NT is the only Clostridium strain enrolled as an anticancer agent to investigate in human trials.

As a radio-enhancing agent, C. novyi-NT spores were used in combination with low-dose radiation, which overcome the hypoxic barriers and resulted in tumor regressions with relatively little toxicity.

Being a bacterium, studies have also shown that T-Cell mediated immunity is enhanced which in turn destroys residual tumor cells, aiding in preventing recurrence.
Intratumor injection of C. novyi has allowed us to reduce doses substantially than Intravenous preparations.

Safety Concerns

Clostridia in the blood stream can be eliminated with the use of antibiotics such as metronidazole. In animal studies, systemic-administered C. novyi-NT spores have no clinical toxicity and were rapidly cleared by the reticuloendothelial system in healthy mice or rabbits.

Meanwhile, toxicosis induced by dose administration of C. novyi-NT spores is manageable in natural tumor-bearing dogs.

Conclusion

Given the advancements in the use of C. novyi– from being used to lyse tumor cells along with other modalities, to being used as a piggy back to deliver drugs into the hypoxic depths of tumors, this new field shows a promising future.

Further scope for study involves controlling the rate of tumor lysis to prevent Tumor Lysis syndrome(which was a common cause of death) and understanding the usage of this technology in solid tumors.

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