A Yale scientist who pioneered a cutting-edge approach to cancer treatment is warning that the field is going off-course - and that drug giants could be making it worse
- A leading Yale scientist whose work helped a cutting-edge approach to cancer called immunotherapy get off the ground is now warning that the field has lost touch with the fundamental science.
- If current trends continue, "we are going to see a lot of negative trials in cancer patients," the researcher, Dr. Lieping Chen, told Business Insider.
- Chen is particularly concerned about an approach that large firms like Bristol-Myers Squibb and Boehringer Ingelheim are taking.
- Yet another pioneering cancer scientist, whose company is focused on this space, said the worries could be unfounded.
The ability to use the body's immune system to attack cancer is one of the most important scientific advances of our time.
The approach, called cancer immunotherapy, has had tremendously positive results in patients, and has prompted hundreds of scientific trials.
But a leading Yale researcher and cancer immunotherapy pioneer is now warning that the field has gone astray, led by drugmakers who have lost sight of its scientific underpinnings.
Drugmakers are rushing to do clinical trials in attempts to "grab a piece" of the trend without doing the fundamental research first to show it's worth it, Dr. Lieping Chen, the co-director of the Cancer Immunology Program at Yale Cancer Center, wrote to Business Insider in an email.
"If this trend continues, we are going to see a lot of negative trials in cancer patients," he said.
Chen said this is particularly evident in the case of cancer immunotherapy drugs that target a protein called LAG-3. These products are being tested out by large firms like Bristol-Myers Squibb and Boehringer Ingelheim, but there's evidence from Chen's team that they're going about it the wrong way, he said.
Targeting proteins in order to fight cancer
Cancer immunotherapy, or immuno-oncology, is rooted in a simple-enough question: Usually, T cells that are part of the immune system recognize and attack foreign invaders - why not in cancer, too?
Back in 1999, Chen helped solve a piece of the puzzle. While working at the Mayo Clinic, the researcher discovered a molecule called PD-L1 that has become a crucial component of immuno-oncology approaches today.
When another protein, PD-1, binds to PD-L1, the phenomenon works like an "off switch" for T cells. This understanding paved the way for drugs called checkpoint inhibitors, which target PD-1, PD-L1, and other proteins so T cells can continue their anti-cancer work.
Checkpoint inhibitors have had startlingly effective results for some cancer patients (though they haven't been able to help everyone) and the trend has swelled the ranks of cancer immunotherapy clinical trials.
Yet not all those clinical trials are grounded in firm-enough scientific fundamentals, Chen said, especially the "quite a few" working in a specific area: LAG-3 inhibitors that block the protein MHC-II.
MHC-II is thought to be the main protein that LAG-3 binds with - so if a drug can stop that interaction, the idea goes, T-cells will then be able to better fight cancer.
Several experimental drugs are trying this approach, Chen said, but it likely won't work.
In research recently published in the peer-reviewed scientific journal Cell, his Yale team found that another protein, FGL1, played a leading role in inhibiting LAG-3 in mouse tumors. (Boehringer Ingelheim was one of the funders of the research, along with the National Institutes of Health.)
Related: A cancer drug that AbbVie acquired in a $10 billion deal is looking more and more like a failure
Experimental drugs could still work
Scientist Frédéric Triebel, who discovered LAG-3, said it's possible the distinction might not matter.
Triebel is also chief scientist and medical officer of Immutep, which calls itself the "global leader in LAG-3 products," and is developing drugs for cancer as well as autoimmunity.
Because antibodies are large molecules, "it is likely that therapeutic antibodies blocking the MHC II binding site are blocking the FGL1 binding site as well," Triebel wrote to Business Insider in an email. It's also unclear whether the cancer products being developed are so specific as to block only interactions between LAG-3 and MHC-II, he said.
In other words, "some of the LAG-3 blocking antibodies being developed in the clinic may block both interactions," Triebel said.
Immutep is collaborating with Merck on one cancer drug focused on LAG-3, and the oncology-focused biotech Symphogen also has a trial in the works, according to the US clinical trials database.
Chen isn't the only scientist to raise concerns about immuno-oncology more generally, or about the lack of scientific understanding of LAG-3.
But Chen's rebuke, laser-focused on the biopharmaeutical industry, is particularly notable because it comes from a founding father of cancer immunotherapy.
"These negative trials will eventually hurt the field with misleading and confusing information," he wrote in an email to Business Insider. Though there's no guarantee his team's approach will work, he noted, it is "guided by new science and discovery rather than speculation."