New advance increasing the effectiveness of immunotherapies for cancer treatment

Harnessing T-cell “stemness” could enhance cancer immunotherapy

A new study led by scientists in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI) sheds light on one way tumors may continue to grow despite the presence of cancer-killing immune cells. The findings, published March 29, 2019, in Science, suggest a way to enhance the effectiveness of immunotherapies for cancer treatment. NCI is part of the National Institutes of Health.

Dying cancer cells release the chemical potassium, which can reach high levels in some tumors. The research team reported that elevated potassium causes T cells to maintain a stem-cell-like quality, or “stemness,” that is closely tied to their ability to eliminate cancer during immunotherapy. The findings suggest that increasing T cells’ exposure to potassium—or mimicking the effects of high potassium—could make cancer immunotherapies more effective.

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Potential of CAR T

Custom CAR T Cells Made to Order

Chimeric antigen receptor (CAR) T cells are about as cutting-edge as cancer care gets today. Having demonstrated the ability to eradicate tumor cells in up to 90% of patients with certain blood cancers, these engineered immune cells became the first class of gene therapy to win FDA approval in 2017—with Novartis’ Kymriah getting the nod in August, followed by Kite Therapeutics’ Yescarta in October.3 But Alexander Marson, MD, PhD, knows these sophisticated cells are capable of so much more.

Marson, an immunologist at the University of California at San Francisco, is exploring this potential by using the CRISPR-Cas9 system to introduce precisely targeted genome modifications. The idea is that by adding or deleting specific genomic sequences, one can make these cells more lethal for tumors but also safer for the patient. Marson’s team recently developed a platform called SLICE4—single-guide RNA (sgRNA) lentiviral infection with Cas9 protein electroporation—to perform diverse CRISPR modifications in many cells in parallel, in hopes of rapidly identifying changes that measurably improve CAR T-cell performance. “We’re pretty good at manufacturing the ‘hardware’ of gene edited cells, and we’re continuing to improve that,” says Marson. “The really interesting thing will be what genetic ‘software’ we can put into them.”

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