Tang Prize Biopharmaceutical Award Winner Rosenberg: Witnessing Tumor Disappearance Inspired Immunotherapy [Interview]

(Central News Agency reporter Hou Zhiying, Washington, June 16) Steven A. Rosenberg, one of the recipients of the Tang Prize in Biopharmaceutical Science, is widely regarded as the 'father of cancer immunotherapy.' Around 50 years ago, while still a resident physician, he serendipitously discovered that a stomach cancer patient previously given a death sentence experienced a miraculous disappearance of tumors years later. Another similar case involving kidney cancer further solidified his resolve to pursue immunotherapy research.

Steven A. Rosenberg, along with Michel Sadelain and Carl H. June, received the 7th Tang Prize in Biopharmaceutical Science for their discoveries and development of tumor-infiltrating lymphocytes (TIL) and chimeric antigen receptor T-cell (CAR-T) therapies.

Born in New York, the 85-year-old Rosenberg currently serves as Chief of the Surgery Branch at the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH). He recently sat down with a CNA reporter in Maryland to recount his journey from a surgical doctor to a pioneer in cancer immunotherapy, speaking with deep compassion for his patients.

Rosenberg began his research early in his career at the National Cancer Institute. He recalled that cancer treatment at the time relied primarily on surgery, radiation, and chemotherapy. As a surgeon, he often believed he had successfully removed tumors, only to later see them reappear in the liver or lungs. 'I realized we needed another way to treat cancer,' he said.

This realization sparked his interest in immunotherapy: fighting disease not with scalpels, radiation, or drugs, but by harnessing the body’s own natural immune system. This path was inspired by several patients he encountered years earlier.

Rosenberg recalled one patient he met while working an emergency shift as a surgical resident. The patient came in with upper abdominal pain, appearing to have gallstones. Reviewing the medical records, Rosenberg discovered the patient had been hospitalized 12 years earlier for stomach cancer. Surgical records showed multiple liver metastases, and biopsies confirmed the diagnosis. Doctors sent the patient home, believing recovery was nearly impossible.

Surprisingly, six months later, the patient began gaining weight. A year later, he returned to work. Twelve years later, when Rosenberg operated to remove the patient’s gallbladder, he found the tumors had completely vanished. Rosenberg speculated that the most likely cause of tumor regression was the patient’s immune system.

Another case involved a boy who received a kidney transplant from a car accident victim. Rosenberg explained that doctors were unaware the donated kidney contained cancer cells. Because transplant recipients must take large doses of immunosuppressants, the kidney cancer originating from the donor organ spread widely in the boy’s body. After stopping the medication, the transplanted kidney triggered a rejection response—but simultaneously, the cancer that had spread from the transplanted kidney disappeared entirely.

These two cases prompted Rosenberg to begin his immunotherapy research in the late 1970s. He began using interleukin-2 (IL-2), a substance known to promote lymphocyte growth. He hypothesized that if cancer-fighting lymphocytes existed in the body, administering IL-2 might stimulate their proliferation. He began testing on late-stage, metastatic cancer patients, and only with the 67th patient did he finally identify the correct treatment protocol.

Rosenberg recalled a 1984 case involving a patient with metastatic melanoma resistant to all available treatments. 'We administered IL-2, and her tumors completely disappeared,' he said. The cancer has not recurred since.

The success of this first case proved immunotherapy was possible—'no longer a huge question mark.' This became the most memorable moment of Rosenberg’s research career and the driving force behind his decades-long perseverance.

Rosenberg’s team went on to treat over 400 patients, confirming that this method could indeed cause tumor regression in melanoma patients. The team then began investigating the mechanism of IL-2.

Since IL-2 was known to be a lymphocyte growth factor, the team began studying T cells—'killer lymphocytes' present in various organs. They developed a new technique to isolate and culture lymphocytes from tumor tissue, naming them 'tumor-infiltrating lymphocytes' (TIL).

Rosenberg explained that in multiple experiments, they found that after eliminating the patient’s existing immune system, they could infuse large quantities of TIL cells extracted from the patient’s own tumor, effectively replacing the old immune system. The results confirmed that these cells successfully eradicated tumors—marking the first time lymphocytes were proven to cause cancer regression.

These observations laid the foundation for Rosenberg’s subsequent research. He emphasized that the Tang Prize recognition was not only for using patient-derived cells directly but also for the ability to genetically modify these cells to enhance their anti-cancer activity.

Rosenberg noted that simply administering lymphocytes was insufficient. The procedure required precise conditions: first, eliminating 'natural immune responses' in the patient that hinder lymphocyte function—such as regulatory T cells and myeloid-derived suppressor cells—before injecting the TIL cells.

When properly executed, this process successfully caused tumors to regress in the liver, lungs, and throughout the body. According to their 2011 published data, among over 400 patients, 56% showed tumor regression, and 25% experienced complete and durable remission. This study definitively established that immunotherapy could cure melanoma patients.

However, Rosenberg admitted that while effective for melanoma and kidney cancer, this method has not worked for solid epithelial cancers—the 'common killers' responsible for 90% of cancer deaths.

He noted that recent papers from his team offer a glimmer of hope. By targeting multiple antigens and using cells with stem cell-like properties that rapidly divide upon entering the body, 'we are now able to achieve tumor regression in about 25% of patients with more common cancers.'

Rosenberg emphasized that every cancer results from accumulated genetic mutations. The advantage of targeting these mutations is that 'we no longer need to distinguish between breast cancer and colon cancer—this is essentially a method that can treat all cancers.'

He added that since discovering this approach for epithelial cancers, they have seen positive results not only in melanoma and kidney cancer but also in colon, pancreatic, and other cancers, including highly effective outcomes in breast cancer. 'We are actively working on these common cancers and seeking ways to strengthen the immune system so this therapy can benefit more patients.'

Reflecting on his decades-long research career, Rosenberg said, 'One must immerse oneself in the scientific pursuit of solving problems, with laser-like focus, to overcome the challenges and solve them.' This, he believes, is the key to his success. (Editor: Tang Sheng-yang) 1150616

Stand with the truth. Every contribution you make helps safeguard press freedom.

Download the CNA 'First News' app to stay updated.

Text, images, and videos on this website may not be reproduced, broadcast, or transmitted without authorization.