Predicting If an Immune Checkpoint Drug Will Work

Drugs that activate the immune system to attack cancer in a process known as immune checkpoint blockade (ICB) are a focus of intense investigation. A number of them are already approved by the U.S. Food and Drug Administration (FDA) for various cancers; namely, the anti-CTLA4 antibody ipilimumab (Yervoy), two anti-PD-1 antibodies: pembrolizumab (Keytruda) and nivolumab (Opdivo), and three anti-PD-L1 drugs: atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These ICB drugs have the potential to induce durable cancer regressions, but the majority of cancer patients just do not respond to them at all.

Biomarkers, signature molecules in the blood or other tissue, can sometimes be used to predict a patient’s response to a given treatment. But no reliable biomarkers exist for ICB, and this is a serious concern. Patients who may really benefit from ICB could be overlooked, and patients who are not likely to respond may receive useless (and very expensive) ICB treatment.

Most potential response predictors that have already been identified are not yet useful for one or all of the following reasons: they are not extensively validated, their significance is still uncertain and may differ from one cancer (or even one patient) to another, or they are technically challenging for routine use. These markers are addressed below. Continue reading…

A Gut Feeling: Bacteria in Your Gut May Affect Cancer Treatment

The human gut contains hundreds of species bacteria, which are known to contribute to various bodily functions (such as digestion, of course!) but they also shape our immune system. Now, recent research has revealed how our microbiomes (the abundant bacteria living in our bodies) may affect the efficacy of immune checkpoint blockade (ICB) in cancer treatment.

How it started: about two years ago, an American group of scientists led by Thomas Gajewski of the University of Chicago noticed that melanoma (and some other cancers’) growth in mice was influenced heavily by the type of bacteria found in the mouse gut. They worked with mice purchased from two different vendors, and realized that mice from one vendor had consistently slower-growing tumors. Bifidobacterium bacteria present in the mouse gut were pinpointed to be the culprit, because transfer of Bifidobacterium to mice that did not have it was able to slow down melanoma growth. Treatment with an immune anti-PD-L1 drug was effective in mice that had the bacteria, but not in mice lacking it. Continue reading…