Breakthrough cancer immunotherapy treatments to be ‘curative’ by 2025 says prominent research head
Summary: Cancer immunotherapy treatments and other approaches to cure nearly all cancers within 8 years says Dr. Gilliland, a prominent cancer research head. [This article first appeared on LongevityFacts. Author: Brady Hartman. ]
Gary Gilliland, M.D., Ph.D. is the President and Director, Fred Hutchinson Cancer Research Center (FHCRC) and in an opinion piece published at the beginning of this month, writes
“I’ve gone on record to say that by 2025, cancer researchers will have developed curative therapeutic approaches for most if not all cancers.”
Gilliland says this will be made possible in large part due to “Next-Generation Immunotherapy” advances in treatments that stimulate the bodies own immune system to fight cancer.
Dr. Gilliland bases his optimism on the accelerated advancements of cancer treatments over the last few years, most notably in targeted cancer therapies such as immunotherapies, of which CAR T cell therapy is the most famous.
Gilliland writes glowingly of CAR T cell therapies and other immunotherapies such as the checkpoint inhibitor named Avelumab which works by blocking a molecule called PD-L1. Programmed death-ligand 1 (PD-L1) triggers an off-switch on cancer patients’ immune cells. On the other hand, blocking it enables the immune system to kill off tumors.
Gilliland adds that
“2017 was a landmark year for accelerating cancer cures, ushering in a spate of new FDA approvals for cancer drugs. These include approval of two different CAR T-cell therapies — a type of cancer immunotherapy that uses a patient’s own engineered immune cells to attack and kill cancer cells.”
Cancer is a disease of aging. About half of the population of industrialized countries will develop cancer during their lifetime – typically, between the ages of 40 and 80. Just under 8 million people worldwide die of cancer every year.
Reasoning Behind Cancer Immunotherapy
Cancer immunotherapy got off to a rocky start until the advent of checkpoint inhibitors and CAR T-cell therapy. The field has advanced, and some analysts predict that the majority of all cancers in the industrialized world will eventually be managed with cancer immunotherapies.
Young people rarely get cancer due in part to their robust immune systems. A healthy immune system continually searches for cancerous and precancerous cells, destroying them before they get out of hand. However, our immune systems decline as we age, due mostly to declining function of our thymus, the organ that trains immune system cells.
Cancer immunotherapy stimulates the patient’s immune system to fight tumors, attempting to restore the immune system to the robustness of its youth. Mobilizing the immune system against cancer is a simple concept that is complicated in execution.
Pioneering Days of Cancer Immunotherapy
Pioneering attempts at immunotherapy involved giving patients cytokines to stimulate the immune system. In these early attempts at immunotherapy, the immune system attacked the entire body – a phenomenon known as ‘cytokine storm’ – that sometimes killed patients. Oncologists learned from these failed experiments and observed that some patients had good long-term responses when their bodies overcame the cytokine storms and eradicated the tumors. Additionally, scientists noticed that cytokine treatment provided long-term protection against recurrence, something that traditional cancer treatment does only half the time.
Doctors still use cytokine treatments, however, reserve them for limited types of cancer in relatively healthy patients that can withstand the side effects.
Cancer Immunotherapy
Checkpoint Inhibitors
A breakthrough came when cancer researchers realized that immunotherapies must not only stimulate the immune system but also suppress the checkpoint proteins that cancers use to block the immune system. Avelumab is one of the latest in a long line of checkpoint inhibitors that accomplish the latter.
Checkpoint inhibitors and more refined immunotherapies put the search for a cancer cure on the fast track. As Gilliland puts it,
“I’ve seen more progress in the field in the last few years than in the previous five decades.”
The biotech firm Medarex released one of the first checkpoint inhibitors called ipilimumab that was approved by the FDA in 2011 for the treatment of melanoma, a type of skin cancer. Ipilimumab (Yervoy) is an antibody to a protein called CTLA-4. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein receptor that functions as an immune checkpoint and suppresses immune responses. Ipilimumab has had good results in treating advanced metastatic melanoma, a cancer with a historically low 10-year survival rate.
Although ipilimumab occasionally causes severe and sometimes fatal immune reactions, it is better tolerated than cytokines. Bristol-Myers Squibb (BMS) also released a second antibody which works as a checkpoint inhibitor called nivolumab (Opdivo). Nivolumab blocks a signal that would have prevented T cells from attacking a cancer cell and enables the immune system to fight the tumor. Nivolumab targets another checkpoint protein called PD1 and is more selective in mobilizing the immune system against tumors.
Even more importantly, since nivolumab and ipilimumab work on different parts of the immune system, they work in concert when given together, benefiting more patients than when either is taken alone, in some cases.
The success of the nivolumab and ipilimumab spurred cancer researchers to develop similar drugs to treat cancer. Anti-PD-1 therapies are now approved for use in treating a variety of cancers are being tested on many more. Since nivolumab was released, pharmaceutical firms have released other checkpoint inhibitors including the anti-PD-1 drug called Pembrolizumab (Keytruda) and similar drugs called PD-L1 inhibitors, that include: Atezolizumab (Tecentriq), Avelumab (Bavencio) and Durvalumab (Imfinzi).
CAR T-Cell Therapy
CAR-T cell therapy is perhaps the most famous of immunotherapies and helps boost the immune system to work better against cancer. The labor-intensive procedure involves removing immune cells from a patient and supercharging them using gene editing to fight the tumor more effectively.
CAR-T therapies are very promising, and involved in numerous clinical trials, as Gilliland said
“Right now, we have 12 cellular immunotherapy clinical trials ongoing with 21 more cellular therapy trials in the pipeline slated to open soon.”
CAR stands for chimeric antigen receptors and is an engineered T-cell therapy. While CAR-T is expensive, it has shown good results in treating blood cancers, such as leukemia. Moreover, T cell therapy is showing promise in treating lymphoma. As a recent report shows, at least a dozen clinical trials are testing T cell therapy on other forms of cancer.
Storm Clouds in Immunotherapy Land
Gilliland pointed out the frequently overlooked the harms of cancer immunotherapy. The leading cancer researcher pointed out that in some cases, immunotherapy is not always safer than conventional approaches such as chemotherapy.
“With the goal of making cancer immunotherapy safer, we’re taking the most comprehensive look yet at certain serious side effects and infections that can happen after treatment with CAR T cells. Understanding — and combatting — the unique toxicities associated with CAR T-cell therapy will be key to delivering on the promise of these therapies for more patients.”
Precision Oncology
Selecting the historically best treatments for a specific patient with a particular type of cancer will yield better outcomes for cancer patients, as Dr. Gilliland points out in his opinion piece,
“As we continue to draw new connections between genes and tumor types, precision oncology approaches to treating cancer will become increasingly important and will require at least a terabyte or more of data per patient – enough to fill the storage capacity of eight of the newest smartphones.”
Bottom Line
Given their tolerability and seeming superiority, the FDA and other national regulators have fast-tracked the development of checkpoint inhibitors and other cancer immunotherapies. While cancer researchers are making remarkable progress towards potential cures for the disease, optimism must be tempered because some immunotherapies have reported life-threatening side effects. Hopefully, researchers such as Gilliland will identify and solve these problems.
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References
Cover Photo: Getty Images.
Gary Gilliland. “Cancer Research In 2018: Advances That Will Propel Us To Cures.” LinkedIn. February 1, 2018. Link to article on LinkedIn.
Disclaimer
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