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Checkpoint Inhibitors: Overcoming Resistance

Why do checkpoint inhibitors shrink tumors in some cancer patients and not others? PICI scientists are working together to figure out why.


What are checkpoint inhibitors?

The immune system evolved to fight off disease and infection. But it also has built-in brakes – or checkpoints – that act as a safety catch. Cancer tricks the immune system into pressing on the brakes so that tumor cells can grow unchecked.

Checkpoint inhibitors work against cancer by releasing the brakes on the immune system so it can attack and kill tumors more efficiently.

The FDA first approved checkpoint inhibitors in 2011. Since then, they have become first-line treatments for patients with skin, lung and other types of cancer.

Building on a Nobel Prize winning idea

In 2018, the Nobel Prize committee awarded its first honor for any immunotherapy treatment to the pioneers of checkpoint inhibitors. PICI Director James Allison, PhD, at MD Anderson Cancer Center won the award for his work on CTLA-4, a protein also characterized in seminal work published by PICI vice chair and former CEO Jeffrey Bluestone, PhD.

With this early success as a foundation, PICI scientists turned their focus on improving response to checkpoint immune therapy so it can benefit more cancer patients.

Currently, the drugs only work for a fifth of patients. In some cancer types, none at all. Some cancers remain resistant or develop resistance over time.

What We’re Doing

PICI is conducting studies in multiple cancers – including melanoma, pancreatic cancer and breast cancer – to uncover how and why patients respond or not to these treatments.

We bring together top researchers, pharma companies who make the drugs, biotech companies that are creating new treatments and other nonprofits to support the effort.

Our partner institutions generate data through PICI studies and clinical trials. From there, our internal informatics team takes the data and analyzes it to develop new hypotheses and discover insights. Their work reveals larger patterns that tell us how the immune system reacts to cancer and checkpoint inhibitors.

That information can then be used to pinpoint biomarkers for response to checkpoint immune therapy. Biomarkers are clues that tell us who might benefit the most from treatment with checkpoint inhibitors and when the treatment will work most effectively.

The end goal: get more patients to the finish line with checkpoint inhibition, alone or in combination with other drugs. And to innovate new treatment regimens that cancer can’t outrun