In the winter of 2013, Sue Scott, then 36, had already planned her own funeral. Her cervical cancer was spreading fast. Multiple rounds of chemotherapy, radiation and surgery had all failed. Tumours were invading her liver and colon, and squeezing her ureters.<\/p>\n
Her last chance was to enroll in an experimental trial in which doctors were trying to partially replace patients\u2019 immune systems with T-cells that would specifically attack cancers caused by the human papillomavirus , a common sexually transmitted infection. Within a few months, her tumours completely disappeared.<\/p>\n
This March, she celebrated five years cancer-free and according to her doctors appears to be fully cured. \u201cOne of the biggest rewards is being a source of hope, and being an ear for other people,\u201d said Scott, who works as a realtor in Washington and advocates for cancer patients in her free time.
\nImmunotherapy has already seen some success in blood cancers and melanoma. (Shutterstock)<\/p>\n
The trial at the National Institutes of Health Clinical Center, a US government-funded research hospital, was a breakthrough because it offered the first evidence that immunotherapy, which has already seen some success in blood cancers and melanoma, could work against cervical cancer.<\/p>\n
A closer examination of why Scott\u2019s cells worked so well has also led to a new discovery that may be helpful in killing other kinds of solid tumours. Lead investigator Christian Hinrichs of the National Cancer Institute told Scott the news at her follow-up visit to the NIH in February.<\/p>\n
\u201cStraight out of you, we got that gene sequence and now we can put it in anyone\u2019s cells and make their cells attack cancer the same way,\u201d he said. \u201cSo that is something we are working on, trying to bring it to the clinic to see if it will work.\u201d<\/p>\n
Doctor survived cancer
\nThe trial was unusual in another way, too. Hinrichs, 46, is a cancer survivor himself. He had an ocular melanoma, a rare kind of cancer that affects six in every one million people. The small, cancerous spot was discovered in his right eye when he was in his late 20s, then a young cancer surgeon at the start of a promising career.<\/p>\n
He underwent nearly a dozen radiation and laser treatments, each time believing the cancer was gone. But it always came back. Finally, the only choice was to remove the affected eye, a surgery he underwent in 2005. \u201cHaving experienced cancer and having worried about it coming back influences how you do research,\u201d said Hinrichs. \u201cI really wanted treatments where if the cancer came back, we would have a solution to that problem.\u201d
\nCAR-T cell therapies target blood cancers on the surface of the cells so it is easy for immune cells to find and target the harmful cells. (Shutterstock)<\/p>\n
Seeking a target
\nA person\u2019s immune system will naturally try to kill off any invader, including cancer, but usually falls short because tumours can mutate, hide, or simply overpower the white blood cells that lead the attack, known as T-cells. Immunotherapies that have seen widespread success, such as chimeric antigen receptor (CAR-T) cell therapies, mainly target blood cancers like lymphoma, myeloma and leukemia, which have a tumour antigen \u2014 like a flag or a signal \u2014 on the surface of the cells so it is easy for immune cells to find and target the harmful cells.<\/p>\n
But many common cancers lack this clear, surface signal. Hinrichs\u2019 approach focuses on HPV tumours because they contain viral antigens that the immune system can easily recognise. \u201cWhat is very appealing about this cancer is the virus is right in the cancer,\u201d explained Miriam Merad, professor of oncological science at the Icahn School of Medicine at Mount Sinai in New York.<\/p>\n
Merad, who is not involved with Hinrichs\u2019 work, described his approach as \u201cvery clever\u201d and \u201cabsolutely critical\u201d to unlocking the mystery of why some people respond to immunotherapy and others do not.<\/p>\n
Stunning response, or failure
\nIn Scott\u2019s trial, the strategy was to surgically remove one of her tumours, and isolate the T-cells that were already trying to attack it. Researchers took these tumour-infiltrating lymphocytes (TILs) and grew billions of them to re-infuse in her blood, creating an army of immune fighters.<\/p>\n
Besides Scott, it worked for one other patient, Aricca Wallace, now a 41-year-old mother of two teenage boys in Kansas City, Missouri and also considered fully cured after five years. But the approach failed for the other 16 women in the trial.<\/p>\n
To explore what had worked and why, Hinrichs took another look at the cells that were infused in Scott and Wallace. He found they indeed were targeting HPV. But in Wallace, most of the T-cells were intent on destroying abnormal proteins that were unique to her tumour.<\/p>\n
And in Scott, about two-thirds of the cells that cleared away her cancer were all targeting another tumour signal, a protein called KK-LC-1. This protein is also expressed in cancers that currently affect about a half million people worldwide, including some triple negative breast cancers \u2014 one of the most stubborn and lethal forms of breast cancer \u2014 certain stomach cancers, non-small cell lung cancers and cervical cancers.<\/p>\n","protected":false},"excerpt":{"rendered":"
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