Dr. Brahmer on Immunotherapy Beyond PD-1/L1 in NSCLC

Julie R. Brahmer, MD
Published: Tuesday, Feb 12, 2019



Julie R. Brahmer, MD, co-director of the Upper Aerodigestive Department in the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medicine, discusses the potential for immunotherapy beyond the PD-1 and PD-L1 checkpoints in the treatment of patients with non–small cell lung cancer (NSCLC).

To move beyond PD-1 and PD-L1 checkpoints, researchers need to better understand the mechanisms of resistance and lack of response to immunotherapy in patients with NSCLC, Brahmer says. This falls in line with the precision medicine approach that oncologists are trying to adopt across many tumor types. Do the patient’s T cells just need to be revved up with another drug or engineered in a way that allows them to target an abnormality in the cells? Chimeric antigen receptor T cells have had a dramatic impact in some hematologic malignancies, mainly in heavily pretreated patients. Although this benefit has not yet been seen in solid tumors, Brahmer notes there might be a place for this approach in lung cancer.

In addition, researchers could potentially develop a personalized vaccine that would teach the T cells what to target. If the patient’s T cells are ready to respond, a drug like PEGylated IL-10 (pegilodecakin) could be used to jumpstart them, Brahmer adds. This is an area of ongoing research.
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Julie R. Brahmer, MD, co-director of the Upper Aerodigestive Department in the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medicine, discusses the potential for immunotherapy beyond the PD-1 and PD-L1 checkpoints in the treatment of patients with non–small cell lung cancer (NSCLC).

To move beyond PD-1 and PD-L1 checkpoints, researchers need to better understand the mechanisms of resistance and lack of response to immunotherapy in patients with NSCLC, Brahmer says. This falls in line with the precision medicine approach that oncologists are trying to adopt across many tumor types. Do the patient’s T cells just need to be revved up with another drug or engineered in a way that allows them to target an abnormality in the cells? Chimeric antigen receptor T cells have had a dramatic impact in some hematologic malignancies, mainly in heavily pretreated patients. Although this benefit has not yet been seen in solid tumors, Brahmer notes there might be a place for this approach in lung cancer.

In addition, researchers could potentially develop a personalized vaccine that would teach the T cells what to target. If the patient’s T cells are ready to respond, a drug like PEGylated IL-10 (pegilodecakin) could be used to jumpstart them, Brahmer adds. This is an area of ongoing research.



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