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Our friend has died

Dr. Ralf Kleef - 1961 - 2021

With great sadness, we share news that the cancer immunotherapist, Ralf Kleef, M.D., passed away on Monday, December 6, 2021. The underlying cause of death was COVID-19.

Kleef was born in northern Germany and had practiced in Vienna for over a dozen years. One year ago, he relocated his clinic to Budapest, Hungary. But he still administered part of his treatment in Vienna. It was there, during a raging COVID-19 outbreak, that he and his wife, Krisztina, came down with the virus on November 1. Thankfully, his wife soon recovered, but Kleef’s condition continuously worsened. At first, he was treated at home, but he developed a fever of 104º F (40º C). On Wednesday, November 10, he was rushed to a Viennese hospital. There, he was diagnosed with pneumonia, secondary to COVID-19, and was sedated and intubated. Although most of his bodily functions remained strong, there was a worsening of his lung infection. On December 5, his right lung collapsed. His doctors tried to drain the lung of fluid but his weakened system could not survive this procedure. He passed away the next morning.

Ralf Kleef was 60 years old. He and his brother were orphans adopted by a family living along the Baltic Sea. He began his medical career in 1980 as an ambulance driver and nurse specializing in spinally injured patients. From 1984 to 1991, he studied at Ruhr University Bochum, Germany, the Private University Witten/Herdecke, Germany, the Medical Faculty of the University of Vienna, and Guy’s Hospital, London. From 1991 to 1994, he received advanced clinical training from E. Dieter Hager, M.D., Ph.D., founder of the BioMed Hospital, and one of the leading figures in complementary medicine in Germany. From 1994 to 1996, Ralf served as a Postdoctoral Research Fellow in Immunology at Memorial Sloan-Kettering Cancer Center, New York City, under the sponsorship of the Cancer Research Institute of New York. His mentor at MSKCC was Lloyd J. Old, M.D., vice president of Sloan-Kettering Institute.

Kleef became a close friend and protégé of Helen Coley Nauts, daughter of William B. Coley, M.D., the American founder of cancer immunotherapy. After a three-year stint at MSKCC, Kleef became a research fellow at the Office of Alternative Medicine (OAM), a branch of the National Institutes of Health. In 1997, he helped organize a large U.S.-sponsored conference of non-conventional cancer treatments.

Kleef continued working along these lines for a quarter of a century. He published several landmark papers on the integration of immune checkpoint drugs with CAM treatment. The most important appeared in the journal Cancer Immunology, Immunotherapy in May 2021. This was a case series of 131 patients who were treated consecutively at his clinic in Vienna. Both in terms of its results and its methodology, this was a breakthrough publication. Not only did he report excellent results, but this was the first time that any complementary cancer clinic had provided a complete picture of the outcome of its treatment program. It is common to say that individuals who die before their time are irreplaceable. In the case of Ralf Kleef, however, the world has truly lost a unique figure. We can only hope that those who survive him will build on his legacy and continue his work.

— Ralph W. Moss, PhD


Kleef R, Nagy R, Baierl A, Bacher V, Bojar H, McKee DL, Moss R, Thoennissen NH, Szász M, Bakacs T. Low-dose ipilimumab plus nivolumab combined with IL-2 and hyperthermia in cancer patients with advanced disease: exploratory findings of a case series of 131 stage IV cancers - a retrospective study of a single institution. Cancer Immunol Immunother. 2021 May;70(5):1393-1403. doi: 10.1007/s00262-020-02751-0. Epub 2020 Nov 5. PMID: 33151369 Free PMC article.

Bakacs T, Moss RW, Kleef R, Szasz MA, Anderson CC. Exploiting autoimmunity unleashed by low-dose immune checkpoint blockade to treat advanced cancer. Scand J Immunol. 2019 Dec;90(6):e12821. doi: 10.1111/sji.12821. Epub 2019 Oct 7. PMID: 31589347 Free article. Review.

Kleef R, Moss R, Szasz AM, Bohdjalian A, Bojar H, Bakacs T. Complete Clinical Remission of Stage IV Triple-Negative Breast Cancer Lung Metastasis Administering Low-Dose Immune Checkpoint Blockade in Combination With Hyperthermia and Interleukin-2. Integr Cancer Ther. 2018 Dec;17(4):1297-1303. doi: 10.1177/1534735418794867. Epub 2018 Sep 7. PMID: 30193538 Free PMC article.

Kleef R, Jonas WB, Knogler W, Stenzinger W. Fever, cancer incidence and spontaneous remissions. Neuroimmunomodulation.2001;9:55-64.

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