Earlier this month, in The Onco?Zine Brief, our weekly radio broadcast and podcast, Sonia Portillo and I interviewed Joshua A. Hill, MD, an Associate in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center in Seattle, Washington and an attending physician at the Seattle Cancer Care Alliance, as well as an Assistant Professor at the University of Washington.

We spoke with Doctor Hill about how cancer immunotherapy seeks to harness the power of the immune system to eradicate malignant tissues. And how, after decades of research, a number of cancer immunotherapies have shown great clinical results.

For example, monoclonal antibodies that block key checkpoints on T cells have improved survival in metastatic melanoma and induced anti-tumor effects in other cancers and bispecific antibodies have mediated impressive responses in B-cell acute lymphoblastic leukemia (ALL), and dramatic anti-tumor effects have been observed using adoptive T-cell immunotherapy, increasingly using genetic engineering to create tumor antigen-specific T cells.

But there is ? as with all anticancer therapeutics – risk associated with cancer immunotherapy. This risk can be broadly classified into autoimmune toxicity and cytokine-associated toxicity.

In our conversation Doctor Hill addressed some of the adverse events ? the side effects ? of the treatment with a very new, targeted therapy designed to unleash the immune system to kill cancer.

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The development of these novel treatment can be classified as a truly remarkable breakthroughs based on a better understanding of cancer biology and the power of the immune system.

In his new book, A Cure Within: Scientists Unleashing The Immune System to Kill Cancer, published by Cold Spring Harbor Laboratory Press author Neil Canavan writes about the power of the immune system. But, as veteran journalist with more than 20 years of experience reporting on science and medicine and the past 5 years reporting exclusively on issues related to drug development in cancer, he reflects the often deeply personal relationship with the dreaded disease, emphasizing that there are only a few words like cancer, that have such a visceral ? personal ? impact.

Canavan paints a grim picture by saying that probably everyone over the age of 30 knows someone who is impacted by cancer ? or may be impacted him or herself. “We may know a fried, family member, someone lost too soon,” Canavan writes.”But generally we don?t want to talk about this ? because we don?t understand cancer ? and there is not so much we can do.”

A War against Cancer
Since the early 1970?s there is a ?War against cancer.? We’re indeed fighting this dreadful disease. “But,” asks Canavan, “Are we making progress? ? are we really winning?”

This confrontational question is hard to answer. Defeating cancer remains one of the medical science? greatest challenges. Over the last 30 years we?ve seen many promising treatment options. Some work, some fail. But scientists are not easily giving up on their crusade. And the the public, waiting for a magic bullet or miracle cure for cancer, does not want them to give up either.

For example, despite disappointment in the wake of the interferon hype in the 1980s, public support for science did not wane. The interferon crusade was immediately followed by the believe that interleukin was the major breakthrough in cancer treatment. Unfortunately, while interleukin has indeed been a great tool in stimulating the immune system to fight cancer, it was not the hoped for miracle drug.

Intense interest
While the use of T-cells to fight cancer is by no means a new concept, new developments the clinical applications that has been applied and fine-tuned for decades is new. One thing is clear, whether new or not, there is an intense interest in the progress made as well as the pioneers involved in developing novel treatment options for people affected by cancer.

Cavana’s book is the story of both. He focuses on the revolutionary science of something called cancer immunotherapy ? which includes the CAR-T therapy we talked about earlier with Hill.

Cancer immunotherapy, better known as Immuno-oncology or I/O is still in its infancy. But the concept – mobilizing the immune system to recognize and attack cancer ? has been imagined and – occasionally ? been attempted – for over 100 years.

In the early 1900s, German Nobel Laureate Paul Ehrlich imagined an ideal therapy to treat disease – a drug precisely targeted to an invader, which, if linked to a toxic chemical that would act like a missile – could carry a destructive payload directly to a specific disease.

Ehrlich said that this novel drug would act as a ?Magic Bullet.?

Such a therapy, he theorized, would be ideal for countless diseases, including cancer. And today, while there are a number of very targeted therapies for the treatment of cancer ? It?s only just recently that significant – or as Neil writes ? unprecedented ? progress has been made.

With the use of newly approved immuno-oncology treatments, there are now reports of cancer patients with advanced disease living years beyond all prior expectations. And interestingly enough ? while oncologists generally don?t say that a patient is cured, it seems that these once-terminally ill patients are now considered ?cured?.

This has never happened before. And it means that the way we treat cancer is about to change forever. This revolution, as Cavana calls it, was not sparked by the development of a novel immuno-oncology drug, but by the evolution of an entirely new way of thinking about cancer and how to manage the disease.

In short ? going forward and where possible – oncologists will not use pharmaceutical drugs to treat cancer ? at least not directly. Rather, they will treat a patient?s immune system with a specific drug ? and then the patient?s immune system will be unleashed to kill the cancer.

This evolutionary thinking is based on decades of basic research and billions of dollars of investment designed to build a foundation leading to our current thinking.

A Cure Within: Scientists Unleashing The Immune System to Kill Cancer is a story about a the tenacious few scientists who refused to abandon novel scientific concepts. Based entirely on interviews with medical researchers the book tells the story of the pioneers of immuno-oncology. It?s a story of failure, resurrection and success. But above all, it?s a story about discovery and intuition and cunning. It?s a peek into the lives and thoughts of some of the most gifted men and women ? the medical scientists ? who are, on a daily basis – working hard to find a Cure for Cancer.

And if you wonder…. this book is not a boring textbook. Canavan tells a story about the technology that is ? today ? saving lives. And he shares the story of these amazing ? breathing, thinking, charming, often arrogant but funny ? people who make this possible.

Last Editorial Review: March 3, 2018

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