Learning and Doing

Student Uses Immunotherapy Against Merkel Cell Carcinoma

Olga Afanasiev, Ph.D. ’13, visits the lab of her mentor, Paul Nghiem, M.D., Ph.D. Her work helped the lab secure further funding from the NIH.
Photo: Clare McLean

Paul Nghiem, M.D., Ph.D., remembers the beginning of the project: a phone call from viral immunologist David Koelle, M.D. ’85, Fel. ’92.

Koelle suggested a collaboration on a newly identified virus that causes a rare, lethal skin cancer called Merkel cell carcinoma (MCC). Shortly afterward, Medical Scientist Training Program student Olga Afanasiev, Ph.D. ’13, joined Nghiem’s lab.

Nghiem had tissue and blood samples from MCC patients, and Afanasiev began to use them to isolate T cells. Her objective: to see if these immune-system warriors were sensitized to MCC. “We found that the samples [from MCC patients] did have virus-specific T cells against this tumor, while healthy individuals do not,” she says.

The next step was to figure out why the T cells weren’t killing the cancer. There were a few hypotheses, all of which later proved true: that the T cells were comatose; that they got stuck on the outside of the tumor; that the tumors “hid” from the T cells by downregulating a protein. Then Nghiem and Afanasiev formed a collaboration with Cassian Yee, M.D., Res., Fel. ’92, and Aude Chapuis, M.D., at Fred Hutchinson Cancer Research Center (Chapuis also has an appointment at UW Medicine).

“We were able to rejuvenate the T cells in the lab and purify them using the tools I’d developed during my Ph.D.,” explains Afanasiev. Then the T cells were re-introduced to the patient who donated them, a volunteer with metastatic MCC.

The therapy worked, at least partially — several tumors shrank for good. And the patient didn’t develop new disease for twice as long as is typical in patients who don’t receive enhanced T cells.

“Olga’s work provided the impetus for a significant NIH grant,” says Nghiem. The research continued, even as Afanasiev moved on to complete the last two years of her program as a medical student. But the lesson she took from her Ph.D. lingers.

“One of the most important things in science is interdisciplinary connection. To have really strong collaborations,” she says. “Someday, I hope to follow in Paul’s footsteps with a similar blueprint for my own lab.”

Read our feature on the MSTP.

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