Cornelis J.M. Melief


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Cornelis J.M. Melief, MD, PhD

Leiden University Medical Center & ISA Pharmaceuticals




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2022 Inductee



  Biography  

Cornelis (Kees) JM Melief is Emeritus professor at Leiden University, where he worked for decades on the elucidation of the immunological mechanisms that can lead to effective clinically applicable T cell-based immunotherapy of cancer. Since 2010 he is Chief Scientific Officer (CSO) of ISA Pharmaceuticals, a biotech company specializing in development of synthetic therapeutic cancer vaccines.

He received his Ph.D. degree in 1967 from the University of Amsterdam, where he also received his M.D. degree in 1970. He spent two years (1973/1974) as a postdoctoral fellow at the New England Medical Center (mentor R. S. Schwartz) and the Shields Warren radiation Institute and Dana Farber Cancer Center (Harvard, mentors H.I. Kohn & D.M. Livingston) in Boston. In 1975 he became a staff member of the Netherlands Red Cross Blood Transfusion Service, heading the department of cell-mediated immunology. In 1985 he became head of the Dept. of Tumor Immunology at the Netherlands Cancer Institute in Amsterdam. In 1991 he became head of the Dept. of immunohematology and blood transfusion at Leiden University Medical Center, also establishing and heading the tumor immunology group in the department. Of his many contributions to basic immunology, including work in mouse models, and clinical immunology, the most striking highlights are the eradication of large vascularized mouse tumors by adoptive transfer of cytotoxic T lymphocytes (CTL) directed against a molecularly defined T cell epitope of an oncogene-encoded protein in 1989 (Cell) as well as the discovery that T cell help for cytotoxic T lymphocyte induction involves cognate interaction between CD40 ligand on T helper cells and CD40 on Dendritic Cells in 1998 (Nature). This is now recognized as a major pathway of CTL induction in non-inflammatory conditions. In the same year his group published that CD4+ T cell help was crucial in CTL-mediated eradication of an experimental MHC class II negative mouse tumor. In recent years effective immunotherapy of tumors with synthetic long peptides (SLP) was developed in mouse and rabbit models. This has led to the implementation of clinical trials in patients with premalignant disease or cancer of viral origin. Clinical effectiveness was shown in the treatment of patients with premalignant established lesions caused by high risk human papilloma virus type 16 (HPV 16) (NEJM, 2009; CCR 2016). Weaker vaccine-induced T cell responses in patients with recurrent or metastatic cervical cancer were markedly increased to the levels seen in patients with premalignant disease by combination of HPV SLP vaccination and standard carboplatin and paclitaxel chemotherapy, associated with chemotherapy-induced depletion of myeloid-derived suppressor cells in the absence of T cell depletion (Science Transl. Med., 2016 & 2020). Through such observations, Kees Melief is now a champion of combination immunotherapy of cancer, using optimal target antigen selection for therapeutic vaccination with SLP (shared neo-antigens, over-expressed antigens such as PRAME, viral antigens), chemotherapy, checkpoint blocking and/or use of agonists stimulating selected members of the TNFR family such as CD27 (first described by the Melief group in 1987), CD40 and CD137. Kees Melief is a recipient of the William B Coley award of CRI, the lifetime achievement award of the European cancer immunotherapy organization (CIMT), the ESMO Immuno-Oncology award and the AACR Lloyd Old Cancer Immunology award.