Has nanotechnology failed cancer patients?

Based on recent news, scientific publications and clinical trial results, one might conclude that the cancer nanotechnology industry is dead. As the CEO of CytImmune, a clinical phase nanomedicine company, I want to set the record straight, nanotechnology continues to be the only path leading to a treatment solution that offers patients better outcomes with significantly reduced short and long term side effects.

A brief history of failure

From Cerulean to BIND, leading companies in the cancer nanotechnology industry have reported nothing but bad news over the last few years. Clinical trials examining biodegradable polymers, micelles and liposomes have demonstrated these therapies offer marginal benefit to patients at best. And in some studies, patient responses have been less effective than giving chemotherapy alone. In April, 2016,  Nature published an article reporting that after  a billion dollars of investment and a decade of research, we  have made no significant progress toward the development of a nanotechnology that can effectively target tumors and deliver positive clinical outcomes.

Milestones for success

There are seven key milestones that nanotechnology must reach to achieve success. Of the seven milestones, most scientists agree the industry has achieved six. We have been able to engineer nanoparticles that:

  • Are safe to inject into a human and can to travel to any part of the body through the circulatory system;
  • Can be manufactured in large enough quantities to be clinically useful;
  • Selectively target cells and tissues based on biomarkers;
  • Carry and deliver small and large molecule cancer-killing payloads;
  • Shield the body from the side effects of toxic cancer-killing agents; and
  • Concentrate at the site of solid tumors, leaving healthy tissues unharmed.

If we can put cancer killing agents on nanoparticles and safely deliver them to the site of tumors, why aren’t the clinical results better? The answer lies in the physical environment created by the natural biology of every solid tumor.

The tumor micro-environment is the key

Every tumor needs blood to survive. Blood brings oxygen and nutrients to the cancer cells growing inside the tumor. For this reason, all tumors secrete signals to make blood vessels grow into the tumor from surrounding tissues. These blood vessels are not cancerous themselves. In fact, they are perfectly normal, except for one physical flaw—they have small holes (200-400nm in size). Red blood cells are too large to get through these small holes, but fluid and other blood components easily pass through. Nanoparticles (typically 20-50nm) can also transit these small holes, which is why many scientists thought they might become a vehicle to deliver toxic drugs more safely to tumors.

However, as these leaky blood vessels pump fluid into the tumor, the tumor develops a high internal pressure, like a balloon that’s been filled with water. This pressure pushes outward, driving any invading nanoparticles to the periphery of the tumor. The same effect occurs when an individual receives chemotherapy. We see tumors shrink from the outside when we administer chemotherapy, and then grow again after the chemotherapy is stopped, because the systemically administered cancer therapies are unable to reach the cancer cells at the core of the tumor.

The Seventh Challenge

This brings us to the final challenge that any viable nanotechnology must conquer.

  • Find a way to overcome the internal pressure inside solid tumors, enabling a nanomedicine to reach and kill the cancer cells deep inside the tumor.

The most promising cancer nanomedicines tested in Phase II clinical trials to date have successfully accomplished the first six milestones. Not one of these nanomedicine constructs addressed the tumor’s internal pressure, and that is why they failed. The nanotechnology that achieves all seven milestones will succeed in improving both cancer patient outcomes and patient quality of life.

CytImmune’s Solution to the Seventh Challenge

There is only one known class of drugs that can eliminate the high-pressure gradient inside tumors, vascular disrupting agents (VDAs). Tumor Necrosis Factor (TNF) is the strongest known VDA. An 85% response rate has been observed when TNF is given locally to patients along with chemotherapy. Unfortunately, TNF and other drugs in this class have been far too toxic to administer systemically until now.

CytImmune’s nanotechnology, Aurimune, employs Tumor Necrosis Factor (TNF) to meet the seventh challenge. Aurimune is able to safely carry the highly toxic TNF through the body’s circulatory system and into the tumor. Where other nanotechnologies fail, CytImmune’s technology uses TNF to break down the tumor’s high pressure gradient. This allows nanoparticles and even follow-on therapies to penetrate deep into the tumor to kill cancer cells, rather than only killing the outer shell of the tumor.

It is ironic that other nanotechnology companies failed to grasp the importance of the tumor’s internal pressure gradient, yet nanotechnology is the only vehicle able to deliver a highly toxic VDA into the tumor. As the research and medical communities come to realize the importance of overcoming the tumor’s internal pressure, the many benefits of nanotechnology may finally be realized for cancer patients.

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