Why checkpoint inhibitors fall short for some types of cancer

The big news from the recent American Society of Clinical Oncology meeting has been largely about immunotherapy drugs, also known as checkpoint inhibitors. These drugs have been shown to be effective in prolonging life in patients with some types of cancer, such as lung cancer and melanoma, but not others, such as colorectal and prostate cancer.

Lab Land asked oncologist Bradley Carthon and immunology researcher Haydn Kissick why. Both Carthon’s clinical work and Kissick’s lab research on prostate cancer are featured in the new issue of Winship magazine, but the prostate feature just touches on checkpoint inhibitors briefly.

Carthon says the reason checkpoint inhibitors haven’t moved the needle with prostate cancer is “likely due to the absence of infiltration of the prostatic tissue by tumor-associated lymphocytes.”

Checkpoint inhibitors are supposed to unleash the immune system, but if the immune cells aren’t in contact with the cancer cells so that the drugs can spur them into action, they won’t help much. Carthon says: “The answer may be to ‘prime’ the prostate with an agent, then introduce the checkpoint inhibitors.”

One proposal has been that cancers that get a lot of mutations, such as lung cancer and melanoma, (since they are triggered by DNA-damaging agents in tobacco smoke or UV light) stimulate the immune system better. The differences between the cancer cells and the healthy cells are clearer. Research (NEJM paper link) on some forms of colorectal cancer caused by a defect in DNA repair supports this idea.

Kissick suggests that a combination of the therapeutic vaccine-type approaches he has been investigating combined with immunotherapy drugs could be effective. Working with urologist Martin Sanda and Emory Vaccine Center director Rafi Ahmed, Kissick is sequencing the genomes from prostate cancers, and compiling for each one a list of “epitopes”: potential handles that the immune system could grab onto and recognize. Many of the epitopes come from the mutations that accumulate in the cancer cells. Kissick envisions a vaccine approach resembling Provenge, but customized to the patient’s particular tumor.

“We think it could be possible to tailor an immunotherapy to the cancer and the capabilities of patients’ immune systems,” Kissick says.

Separately, an analysis of mutations in late-stage prostate cancers has revealed the presence of mutations also found in breast cancers. The oncologists quoted in this Wall Street Journal article say that the value of genomic profiling for late-stage prostate cancers may become apparent, like it has for other forms of cancer such as lung cancer.

 

 

 

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Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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