“Instructing the immune system to recognize and kill tumours, an approach termed cancer immunotherapy, has transformed the clinical treatment of certain types of malignancy. Prominent among these therapies are immune-checkpoint inhibitors, which block the action of proteins that dampen immune-cell responses against tumours. For example, antibodies can be used to interfere with the inhibitory protein PD-1, which is present on T cells, a type of immune cell that attacks tumours. Immune-checkpoint inhibitors have been most successfully used to treat cancers, such as melanomas, that are well infiltrated by T cells and have a large number of genetic mutations. A subset of these mutations might generate neoantigens — altered protein sequences that are uniquely produced in cancer cells and are recognized as foreign by the immune system.”
“In a new study by Yale Cancer Center, scientists suggest that as the number of clinical trials in cancer immunotherapy grows exponentially, some caution should be exercised as we continue to better understand the biology of these new therapeutic targets. The findings are published today in the journal Cell.
“Researchers around the world have been racing to create therapies that unleash the power of our immune systems against cancer. The most successful of these immunotherapies, which target a molecular pathway known as PD-1/PD-L1, have brightened the landscape for many people suffering with lung cancer and other types of tumors.”
“Cancer has an insidious talent for evading the natural defenses that should destroy it. What if we could find ways to help the immune system fight back?
“It has begun to happen. The growing field of immunotherapy is profoundly changing cancer treatment and has rescued many people with advanced malignancies that not long ago would have been a death sentence.”
“Individuals with an inherited form of skin cancer often have a poor prognosis. The type of immunotherapy that was awarded this year’s Nobel Prize in Physiology or Medicine is, however, particularly effective in this patient group, research from Karolinska Institutet in Sweden shows. The study is published in the Journal of Medical Genetics.
“Congenital mutations of the CDKN2A gene are the strongest known risk factors for inherited skin cancer. Individuals with melanoma who carry mutations in this gene also have poor prognosis, according to previous research.”
Immunotherapy includes a number of strategies that harness the immune system to help treat disease. Immunotherapy for cancer, as we know it, now relies on the activation of specific immune system cells known as T cells. Cancer drugs called immune checkpoint inhibitors act by removing the brakes imposed on T cells by tumors or by the body’s natural mechanisms for limiting their activation to prevent autoimmune disease.
In recent years, the U.S. Food and Drug Administration (FDA) has approved several immune checkpoint drugs for the treatment of various cancers. These drugs target proteins involved in activating the T cell response: PD-1, PD-L1, and CTLA4. Many clinical trials are testing drugs that target other immune checkpoint proteins (OX40, B7-H3, and LAG3, to name just a few), but no notable successes have been reported so far.
Now, some clinical investigators have turned their attention to a different arm of the immune system that could help treat cancer. Continue reading…
“AstraZeneca’s immunotherapy drug Imfinzi cut the risk of death in patients with mid-stage lung cancer by nearly a third in a closely watched clinical study, reinforcing the case for using the drug in earlier disease.
“The encouraging overall survival data boosts prospects for a medicine that was approved this week in Europe and has already had a promising U.S. commercial launch, based on its ability to slow disease progression.”
“Combined immunotherapy with two checkpoint inhibitors — nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) — has shown ‘clinically meaningful’ efficacy in patients with asymptomatic, untreated melanoma metastases to the brain, according to a report regarding new data from the CheckMate 204 open-label phase 2 study.
” ‘Although current practice is to start with surgery, stereotactic radiotherapy, or both followed by immunotherapy or targeted agents, our results support the initiation of immunotherapy to achieve prompt control of both extracranial and brain metastases,’ write the authors.”
“The first patient has been dosed in a phase I/II open-label, multicenter trial investigating a novel immunotherapy combination in patients with newly diagnosed glioblastoma (GBM). Fifty patients have been accrued in the trial, as of May 31, 2018, which will be conducted at 25 sites across the nation.
“This study aims to investigate the efficacy of INO-5401, a T-cell activating immunotherapy agent encoding multiple antigens in GBM, and INO-9012, an immune activator encoding IL-12, in combination with the PD-1 inhibitor cemiplimab (REGN2810).”