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Lloyd J. Old, ‘Father of Modern Cancer Immunology,’ Dies at 78

Rosenthal, Eric T.

doi: 10.1097/01.COT.0000411543.03220.18
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Lloyd J. Old, MD, the persevering pioneer of modern cancer immunology, died Nov. 28 from prostate cancer at age 78 at home in New York City.

He was diagnosed in late-2010, and began cutting back on some of his administrative responsibilities earlier this year. But he remained active scientifically and spoke with his colleagues on a regular basis up until the time of his death, which was unexpected, said those who were both good friends and colleagues of the mild-mannered visionary who stood steadfast in his belief that the body's own immune system could be used to kill cancer cells.

Considered one of the founders of tumor immunology, Dr. Old made several seminal discoveries and suffered some setbacks over the years until the field of immunology joined surgery, radiation, and chemotherapy as a legitimate and standard cancer treatment modality.

He spent his entire professional career at Memorial Sloan-Kettering Cancer Center (MSKCC) since coming to train there in tumor immunology in 1958 following graduation from the University of California School of Medicine, San Francisco.

He never practiced medicine, but his work in basic science always held the ultimate view that it was supposed to help patients.

Over the years, he held numerous scientific and administrative positions at MSKCC, the Ludwig Institute for Cancer Research (LICR), and the Cancer Research Institute (CRI), the New York City-based nonprofit organization dedicated to advancing scientific efforts to develop immune-based therapies for cancer.

He never practiced medicine, but his work in basic science always held the ultimate view that it was supposed to help patients.

“Lloyd was one of the most cautious scientists,” said the organization's CEO and Director of Scientific Affairs, Jill O'Donnell-Tormey, PhD, who worked with him for the last 25 years.

“He championed human discovery, and never overstated or over-touted discoveries, and was disappointed by those who helped tarnish the field of immunology by overpromising.”

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He made major contributions to immunology through his own work, collaborations with colleagues, and the mentoring of others, she noted, and CRI provided about $200 million in research and training grants since he signed on as Director of its Scientific Advisory Council in 1971. He retained that position until a few months ago, when he was named Founding Scientific and Medical Director and James P. Allison, PhD, Chair of Sloan-Kettering Institute's Immunology Program, became Council Head.

According to Dr. O'Donnell-Tormey, Dr. Old was most proud of establishing the Cancer Vaccine Collaborative (CVC) in 2001, a joint venture between CRI and LICR, when he was serving as director of both institutes, while also directing the New York branch of the Ludwig housed at MSK.

The Collaborative is a coordinated global network of basic and clinical researchers whose goal is to develop effective cancer vaccines focusing on a single antigen, NY-ESO-1.

When Dr. Old stepped down as director earlier this year he was succeeded by Jedd D. Wolchok, MD, PhD, a medical oncologist specializing in metastatic melanoma who directs immunotherapy clinical trials at MSK.

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Discovery of TNF

Dr. Old was probably most noted for his and Elizabeth Carswell's 1975 discovery of tumor necrosis factor (TNF), which showed that a protein could boost immune response and cause some types of tumor cells to die. In addition, his earlier work with Edward A. Boyse, MD, on understanding cell surface markers was an important building block for the entire field.

Old was one of several researchers to identify the tumor-suppressor gene p53, and with Baruj Benacerraf, MD (who later received the Nobel Prize in Physiology or Medicine), showed that the tuberculosis vaccine bacillus Calmette-Guerin could provide some protection against tumors in mice.

Clinical success for immunotherapy had been elusive and suffered setbacks, but, Dr. O'Donnell-Tormey maintains, those setbacks loomed larger because of unrealistic expectations touted by others and hyped in the media, and that to some degree the baby was thrown out with the bath water. “Lloyd stuck to the path and learned more and more without overstating and overblowing, and stacked piece upon piece until we got to where we are today. He knew that sometimes it just takes longer.”

He enjoyed some sense of scientific vindication in 2010 when the FDA approved two cancer immunotherapies—sipuleucel-T (Provenge) for prostate cancer, and ipilimumab (Yervoy) for metastatic melanoma, which was made possible by Jim Allison's work that helped explain how the immune system attacks tumors.

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‘Brilliant, Gentle, Gracious’

Everyone OT spoke with described Dr. Old as brilliant, gentle, and gracious, as well as a giant figure in his field, who always treated them as colleagues even very early in their respective careers.

“He championed human discovery, and never overstated or over-touted discoveries, and was disappointed by those who helped tarnish the field of immunology by overpromising.”

Jill O'Donnell-Tormey, PhD, Cancer Research Institute CEO and Scientific Director

The man who originally planned to be a violinist while growing up in San Francisco was considered a true Renaissance man with wide and varied cultural interests.

One of his greatest talents, noted Dr. O'Donnell-Tormey, was bringing out the talent in others.

Dr. Allison said that in 2004 when he was being recruited from Berkeley by then-MSK President Harold Varmus, MD, he met with Dr. Old and was amazed that the immunologist was aware not only of his recent work but also of his papers going back to the early 1980s.

Jedd Wolchok had no idea that he would someday be heir to Dr. Old's CVC effort when the two first met, he said. Wolchok had just finished his freshman year at Princeton and was undecided between careers in science or economics when he was given the opportunity to spend the summer in the MSK laboratory of Alan N. Houghton, MD, a protégé of Lloyd Old who holds his namesake chair in clinical investigation.

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‘Infectious Commitment’

“When I was 19 and first met Lloyd he had a very important title [Vice President for Research at the Sloan-Kettering Institute] but still greeted me like any other scientist. He changed so many peoples' lives in such a positive way, and had an infectious commitment to cancer immunology. His devotion and contributions are now being continued through the work of others,” Dr. Wolchok said.

“After receiving my MD and PhD, I returned to Memorial for my oncology fellowship, and my mentor Alan was trained by Lloyd and I was trained by both of them and I felt as if this was a translational research family that I became part of.”

Dr. Wolchok said that Dr. Old believed that every patient should be studied as much as possible and that much could be learned about immunology from individual patients who did well or who didn't respond to immunotherapy.

“He functioned at a very high level, leading international research organizations, and even though he never practiced medicine, if a patient ever needed advice Lloyd was on the phone and would help out by calling the right person.”

Dr. Wolchok noted that the day before this interview he was at a Cancer Research Institute board meeting and even though it was about two weeks after Dr. Old's “there was an emptiness among all of us, and a few of us confessed to having picked up the phone to ask Lloyd something during these last few weeks.”

Dr. Wolchok said that he spoke with Dr. Old often and learned of his death when he had called him at home the day he died.

© 2012 Lippincott Williams & Wilkins, Inc.
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