OV Therapy – The Next Frontier is Closer Than You Think

This fourth in our blog series on the progress of cell and gene therapy for cancer focuses on a treatment that has made huge strides in recent years: Viral Therapy.

What is Viral Therapy?

Using viruses to target disease is a science first contemplated over a hundred years ago, but was not possible until the technology advances we have now virus_fightscancerthat enable genetic engineering. Oncolytic Viral Therapy [OV] made news last year at Duke University when a trial using a modified polio virus effectively destroyed Glioblastoma, a deadly brain cancer. Half the patients, in advanced stages, found themselves in remission. In other studies, a measles virus destroyed severe blood cancer and the maraba virus, related to rabies, reduced the size and spread of melanoma, lung and colon cancers, as well as select brain tumors.

How can a virus fight cancer?

You may be thinking: why would I purposely insert a virus into my body? Viruses are harmless once they are decoded, and there are over 3,500 known viruses with the potential to be therapeutic agents. In laboratory research, viruses proved their ability to spread curative agents rapidly in cancer cells and, at the same time, signal the immune system of a threat, so the body responds with its own army of killer T-cells.

ACGT and OV

Dr. John Bell, ACGT Scientific Advisory Council member, and Research Fellow,  reported in April at the ACGT Scientific Symposium that viral therapy is a powerful 1-2 punch. “The virus attacks the tumor and the immune system comes in to finish the job.”

According to ACGT experts in the field, oncolytic viruses have an exemplary safety record. One of the greater success stories was a 49-year old patient at the end of a 10-year battle with myeloma who has been in remission for 2.5 years after the direct injection of a modified measles virus.

Dr. Bell and his colleagues at the forefront of OV describe viruses as “exquisitely selective” in targeting cancer cells and they are easily engineered to carry corrective genes to destroy or repair damaged genes.

Challenges and Potential

The great challenge ahead is to match the right virus to the cancer, as well as learn how to mass manufacture viral agents to treat large numbers of patients. Perhaps the greatest obstacle researchers face is that many tumors contain sensors that trigger an anti-viral response, to defend against the therapeutic influence of the virus. As we’ve reported before, cancer cells are tenacious in protecting themselves frocancer_revolutionarytreatmentm interference from all types of treatment, including cell and gene therapies; however scientists are closing in on ways to destroy the cancer line of defense.

This science is moving rapidly. Researchers throughout the world are examining the intricate differences between types of cancers to ensure a virus’ ability to penetrate and replicate. At the same time, biotech and pharmaceutical firms are looking closely at the potential for this revolutionary treatment. Novartis, one of the largest drug companies in the world, is backing a therapy using an HIV virus with the hope of FDA approval within the year, and trials using Amgen’s Imlygic, an OV treatment for metastatic melanoma, used in combination with the chemotherapy drug Yervoy, improved life span. Stay tuned!

“There’s no question this field has altered the trajectory of cancer research – we’re moving towards a biologic approach and away from drug and radiation treatment.”    Dr. John Bell, Ottawa Hospital Research Institute

 

CRISPR the Next Frontier in Gene Therapy Cancer Research

In our last blog, we described the progress and promise of CAR-T, an immunotherapy that has been particularly successful with leukemia and lymphoma. As a companion to CAR-T, and all forms of cell and gene therapies, CRISPR is the talk of the scientific town these days and is the next tcell_ssfrontier in genetic medicine.

CRISPR. Sounds like something that belongs in your kitchen, doesn’t it? This science is neither therapy nor treatment. It’s a fantastically precise tool that permits genetic editing. Once we completed mapping the human genome, we have the knowledge, and the technology, to effect change in the base DNA that makes up our unique identity. A small change in that code can make a huge difference in health and longevity.

What is CRISPR technology?

Clustered Regularly Interspaced Short Palindromic Repetition is the actual term, should you have an opportunity to prove your medical mettle in conversation. A simpler translation: molecular medical scissors used to repair or replace a portion of the genetic code. #genomics

The technology was discovered just three years ago when researchers, using a DNA cut and paste method using bacteria to protect against viruses, realized they could also edit human genes. In CRISPR, either the cancerous cell, once cut, will repair itself, or the body’s natural killer T-cells will take aim and destroy diseased cells. Unbelievably simple once the barriers caused by mutated or damaged genes are removed.DNA_scissors

Sounds like Sci-Fi? Well, it is a huge leap into the future. So new that scientists from around the world gathered earlier this year for the first international summit on human gene editing, in Washington DC, and agreed to avoid using the science for human genetic engineering. No test tube animals, no Frankenstein. On the other hand, CRISPR is being used to simulate cancers in laboratory animals, for the purpose of study, and much will be learned in this way.

CAR-T, Immunotherapy and CRISPR

CRISPR has the potential to battle not only disease, but also genetic disorders like allergies or neurological dysfunction. The opportunities are limitless. Our own Scientific Advisory Council member, Dr. Carl June, at the University of Pennsylvania, is heading a research team funded by Facebook financier Sean Parker. Dr. June aims to enhance his pioneering immunotherapy by making even more powerful killer T-cells using the CRISPR scissors. Cells will be edited to bypass cancer’s natural protective obstacles to treatment, known as checkpoint inhibitors. [See our blog on CAR-T.]

“This is the first example of CRISPR in clinical trials in humans, period,” Parker reported at the Forbes Philanthropy Summit in August. This sort of advancement may not have been possible without private funding.

 

gene_editing_ssThe race is on to refine the technique. In China, scientists are studying the potential for CRISPR for lung cancer and have secured approvals for first level trials. In the US, the FDA is expected to approve Phase I trials later this year, with patients suffering melanoma, sarcoma and myeloid cancers. The trials will examine toxicity and side effects as well as patient response.

Treating Cancer Patients

Are there challenges? Of course. Medical interventions, even perfected in the lab, must be refined in practice. Humans have been blessed with powerful immune systems that have been too often neutralized when confronted with cancers, but both CAR-T and CRISPR seek to change all that.

The future is happening right now, and ACGT is still the only non-profit in the nation dedicated exclusively to innovative cell and gene therapies for cancer. Stay tuned!

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