GENETICALLY “supercharging” immune cells, and combining this with a new wonder drug, offers a new way to boost the body’s cancer defences, Melbourne researchers have found.
Peter MacCallum Cancer Centre researchers hope the new treatment combination, tested successfully in animals, will eventually allow cancer patients to be immunised against relapses.
The team combined the anti-PD-1 drug – which blocks the body’s natural instinct to limit an immune response – with T-cells removed, genetically reprogrammed to better recognise cancer, and re-implanted, so they can then continue fighting cancerous cells without the response being “switched off’.
This treatment eradicated tumours in a third of mice with sarcoma, and saw a significant reduction in the growth of tumours in mice with breast cancer.
Associate Professor Phil Darcy, who led the research with Associate Professor Michael Kershaw and Dr Liza John, said the anti-PD-1 drug and the engineered cells were both effective treatments in their own right, but each was limited in the types of cancer they could treat.
Prof Darcy said it was only by combining the two treatments that the immune system’s attack on the cancer could be sustained.
“Either treatment alone didn’t clear any of the tumours; it was only the combination that worked,” he said.
“Like an infection, where your body responds effectively if you’re infected with a virus again, we hope to replicate this in the cancer setting.
“You want to form a memory response, so the T-cells persist for a lifetime in the patient to respond if the cancer comes back.”
The research team, which published their findings in the journal Clinical Cancer Research , aim to replicate their results in animal tests with other solid tumours including prostate, melanoma and colorectal.
Human clinical trials are expected to begin within three years.
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein found on the surface of cells that has a role in regulating the immune system’s response to the cells of the human body by down-regulating the immune system and promoting self tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.
PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells).
PD-1 inhibitors, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer.
A key factor in the development of melanoma is the ability of cancerous cells to evade the body’s natural defenses against foreign and diseased cells. Johns Hopkins scientists are studying how to educate the immune system to recognize and kill melanoma cells in a variety of ways, including arming immune T cells with specific capabilities in detecting melanoma.
Researchers at Johns Hopkins Kimmel Cancer Center are leading the way in developing novel immunotherapies called anti-PD-1 and anti-PD-L1 for people with advanced melanomas. The therapies aim not to kill cancer cells directly but to block a pathway that shields tumor cells from immune system components able and poised to fight cancer.
In 2015, the drugs entered the market.
Last year, the U.S. Food and Drug Administration (FDA) approved two anti-PD-1 checkpoint inhibitors, a type of immunotherapy, for treatment of non-small cell lung cancer (NSCLC) in patients whose cancer has progressed after first-line treatment with chemotherapy. Now, the manufacturers of both drugs, pembrolizumab (made by Merck) and nivolumab (made by Bristol-Myers Squibb; BMS) are intent on expanding the indications for use of their drugs. To this end, they have conducted clinical trials testing each as a first-line treatment (i.e., in previously untreated patients), comparing them to standard chemotherapy.
With results from both companies now made public, it is clear that pembrolizumab (brand name Keytruda) has “won” this phase of the checkpoint drugs war. KEYNOTE-024, the clinical trial that tested pembrolizumab, met its endpoint, improving progression-free survival (PFS) by 4.3 months (10.3 months versus 6.0 months in patients receiving chemotherapy), and improving overall survival as well. Checkmate-026, a similar trial with nivolumab (brand name Opdivo), has not achieved its primary endpoint of improving PFS over chemotherapy.
Do the best you can to live a healthy lifestyle and to avoid environmental causes of cancer so you don’t need a $150K/yr drug some day.