According to Patrick Soon-Shiong, MD, FRCS(C), FACS, there is a basic reason conventional cancer therapy fails so frequently: It is based on the notion that cancer is a monoclonal disease that can be defeated with a single therapy. The reality is that cancer is a multiclonal disease. Targeting and killing any one clone simply encourage the growth and eventual success of treatment-resistant clones.
“We need to rethink how we fight this disease,” said Dr. Soon-Shiong, creator of the Cancer MoonShot 2020 program. “Today we target the cancer, wipe out the immune system and wonder why the cancer wins. We need to target the host, not the cancer. We need to preserve and strengthen the immune system to kill the cancer from the inside.”
Dr. Soon-Shiong discussed the rationale behind his Cancer MoonShot 2020 program Monday morning at AUA2016 during the annual Ramon Guiteras Lecture. The program is a collaborative project that includes pharmaceutical companies, community and academic oncology, and the government. The ultimate goal is to develop a personalized cancer vaccine by 2020 that stimulates and primes the immune system to attack and control cancer.
The current cancer treatment paradigm follows the model developed to target infectious diseases with antibiotics and other agents. But just as antibiotic use gives rise to resistant organisms, chemotherapy and radiotherapy give rise to resistant tumor clones. The time to recurrance is nothing more than the time it takes surviving clones to repopulate the lesion.
Systemic treatments such as high dose chemotherapy wreak havoc throughout the system. A more effective strategy is to use low dose therapy delivered directly into the tumor microenvironment, Dr. Soon-Shiong said. Instead of using the maximum tolerated dose and hoping it is enough, penetrating the tumor microenvironment will allow clinicians to use the maximum effective dose by targeting specific tissues.
Dr. Soon-Shiong transformed this strategy into Abraxis BioScience, maker of Abraxane, a nanoparticle albumin-bound paclitaxel approved for advanced pancreatic cancer, non-small cell lung cancer and breast cancer. Celgene now owns the product.
The next step is to harness the immune system itself to fight cancer.
“I trained as a transplant surgeon and in my world of transplantation I was trying to induce the body not to reject foreign cells,” Dr. Soon-Shiong explained. “Cancer is cancer because it has found a way to beat the immune system. If we can turn the immune system back on, if we can train it to identify the clones that make up your cancer, we can destroy your disease from the inside.”
Genomic programs are uncovering growing numbers of genetic variants seen in different tumors. This genomic information is used to create biological agents designed to target specific mutations. Targeting specific genes is a move in the right direction, Dr. Soon-Shiong said, but it’s not enough.
“It is not the gene that matters, it’s what goes downstream of the gene, proteins, that are the real killers. And those same proteins can be the target for the immune system,” he explained.
Dr. Soon-Shiong has created a novel approach, GPS, that uses whole genomic, proteomic and mass spectroscopy to identify proteins that are specific to each tumor. And he built a public company, NantKwest, to develop the idea.
In the GPS treatment model, individual tumor proteins are used to activate dendritic cells, which are administered as conventional subcutaneous injection. The activated dendritic cells migrate to target tumor cells where they initiate conventional immune responses involving natural killer cells and T-cells to destroy the tumor. The entire process, whole genome analysis to treatment, takes 21 days.
Harnessing the immune system to battle cancer eliminates concerns about the emergence of resistant clones and recurrance of disease. Once the immune system is activated, it continues to attack tumor cells wherever they move through the body. And if new clones appear that the immune system does not recognize, the entire immunotherapy process can be repeated as needed.
“Urology could serve as primary care for this kind of cancer care,” Dr. Soon-Shiong said. “You have the unique opportunity and ability to obtain samples needed and to provide care. This is not theory. We have proof points, patients who have survived for years with pancreatic and other cancers that are supposed to be fatal. The common theme is to protect the immune system.”