There’s been tremendous excitement in the cancer community recently about the life-saving potential of immunotherapy. In this treatment strategy, a patient’s own immune system is enlisted to control and, in some cases, even cure the cancer. But despite many dramatic stories of response, immunotherapy doesn’t work for everyone. A major challenge has been figuring out how to identify with greater precision which patients are most likely to benefit from this new approach, and how to use that information to develop strategies to expand immunotherapy’s potential.
A couple of years ago, I wrote about early progress on this front, highlighting a small study in which NIH-funded researchers were able to predict which people with colorectal and other types of cancer would benefit from an immunotherapy drug called pembrolizumab (Keytruda®). The key seemed to be that tumors with defects affecting the “mismatch repair” pathway were more likely to benefit. Mismatch repair is involved in fixing small glitches that occur when DNA is copied during cell division. If a tumor is deficient in mismatch repair, it contains many more DNA mutations than other tumors—and, as it turns out, immunotherapy appears to be most effective against tumors with many mutations.
Now, I’m pleased to report more promising news from that clinical trial of pembrolizumab, which was expanded to include 86 adults with 12 different types of mismatch repair-deficient cancers that had been previously treated with at least one type of standard therapy . After a year of biweekly infusions, more than half of the patients had their tumors shrink by at least 30 percent—and, even better, 18 had their tumors completely disappear!
Tags: cancer, cancer drugs, cancer genetics, cancer treatment, immune system, immunotherapy, Keytruda, mismatch repair, mismatch-repair deficiency, monoclonal antibody, NCI-MATCH trial, oncology, PD-1, PD-1 inhibitors, pembrolizumab, precision medicine, precision oncology, solid tumor
Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.
A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).
Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.
Tags: adult stem cell therapy, adult stem cells, B cells, blood, blood cells, blood disorders, blood stem cells, bone marrow transplant, bone marrow transplantation, cell reprogramming, endothelial cells, graft versus host disease, hematopoietic stem cells, HSC, HSCs, immune system, immunosuppression, induced Pluripotent Stem cells, iPS cells, iPSCs, leukemia, red blood cells, regenerative medicine, sickle cell disease, stem cells, T cells, transcription factors, white blood cells
It’s an inescapable conclusion from the book of Ecclesiastes that’s become part of popular culture thanks to folk legends Pete Seeger and The Byrds: “To everything (turn, turn, turn), there is a season.” That’s certainly true of viral outbreaks, from the flu-causing influenza virus peaking each year in the winter to polio outbreaks often rising in the summer. What fascinates Micaela Martinez is, while those seasonal patterns of infection have been recognized for decades, nobody really knows why they occur.
Martinez, an infectious disease ecologist at Princeton University, Princeton, NJ, thinks colder weather conditions and the tendency for humans to stay together indoors in winter surely play a role. But she also thinks an important part of the answer might be found in a place most hadn’t thought to look: seasonal changes in the human immune system. Martinez recently received an NIH Director’s 2016 Early Independence Award to explore fluctuations in the body’s biological rhythms over the course of the year and their potential influence on our health.
Tags: biological rhythms, Bridges to the Baccalaureate Program, chickenpox, circadian rhythms, cytomegalovirus, flu, herpes virus, immune system, immunity, immunobiology, infectious disease, infectious disease ecology, influenza, NIH Director’s 2016 Early Independence Award, seasonal flu, shingles, sleep, vaccine, varicella-zoster virus