Big Ideas

Steven Barthel, Ph.D.

When sending a piece of mail, it can’t just be sent in a blank envelope. It needs an address and zip code to ensure proper guidance to its correct destination. If this information was missing, or even erased, it would throw a wrench into the entire delivery system.

This is an analogy Steven Barthel, Ph.D., of Brigham and Women’s Hospital and the Harvard Institute of Medicine, uses to describe how immune cells in the body can be disrupted by cancer cells from reaching their destinations. Immune cells use their own addresses called “homing receptors” to ensure they are headed to the proper place in the body. Research has now shown that cancer cells can corrupt or erase these homing receptors, which prevents immune cells from reaching the cancer and allows tumor cells to spread throughout the body. What’s more, cancer cells themselves can change their own homing receptor addresses to steer them to vital organs, leading to death. Barthel’s research focuses on immunotherapy and how best we can use existing drugs (and create new ones) to boost the immune system and its delivery to better fight off cancer while limiting dangerous side effects.

Before this grant, I had little to no funding to support the proposed research despite extremely interesting and medically significant data. Without support from the V Foundation, none of this would have been possible.

“While recent advances have been extraordinary, current immunotherapy drug regimens unfortunately benefit less than half of patients with advanced melanoma and even less in other cancer types for largely unknown reasons, requiring further understanding of how these drugs actually work,” said Barthel. “Moreover, side effects are not uncommon. These drugs, which target immune checkpoint receptors, bind directly to immune cells to exert their therapeutic activity while avoiding the cancer cells altogether. My research has newly identified that these drugs may unexpectedly also bind directly to the cancer cells to impact tumor-intrinsic properties in previously unknown ways that could be either good or bad for the patient.”

There are multiple potential benefits from this research that excite Barthel. First of all, this research will hopefully lay groundwork for optimizing antibody drugs for patients and improving e-drug potency, efficacy, selectivity and safety. Secondly, findings could be used across many different cancers and by many different categories of researchers, widening its scope.

“Results from this research could lay the foundation for new therapeutic strategies to better boost the immune system to fight cancer, inhibit cancer growth and metastasis and optimize currently available drug regimens,” said Barthel. “It has paradigm-shifting potential in our conceptualization of cancer and its vulnerability to immunotherapy by exploring undescribed and even unexpected pathways of cancer growth and progression.”

While the popularity of immunotherapy continues to grow, researchers like Barthel can still be left in the cold if they don’t secure funding like the 2015 V Scholar Grant Barthel received from the V Foundation. His research would be impossible without it.

“Before this grant, I had little to no funding to support the proposed research despite extremely interesting and medically significant data,” said Barthel. “Without support from the V Foundation, none of this would have been possible.”

And without the support from people across the country, the V Foundation would not be able to award grants to promising researchers like Dr. Barthel. Thanks to your ongoing belief in our work, the most talented researchers in the country continue to move us closer to victory over cancer.