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Cornelis J.M. Melief
Departments of Immunohematology and Blood Transfusion, Leiden University Medical Center,
and ISA Pharmaceuticals, Leiden, the Netherlands
BRIEF CV
The work of Cornelis (Kees) Melief has contributed fundamental insights into the cellular and
molecular mechanisms governing the generation of cytotoxic T lymphocytes (CTL) responses,
the most important adaptive immune response against viruses and tumors. This includes
among the first demonstration of the central role played by Dendritic Cells in the activation of
immune responses, and the provision of the concept of the “licensing” of professional antigen
presenting cell functions by CD4+ T helper cells, required for the optimized induction of CTL
responses. This concept has modified not only our knowledge of the fundamental mechanisms
regulating the generation of spontaneous immune responses, but also the way immunologist
think about the delivery of efficacious vaccines. Cees Melief has also pioneered the use the of
CTL-dependent responses in adoptive immunotherapy of cancer, providing the first evidence
that CTLs specific for an oncogene tumor antigen could eradicate large vascularized tumors in
mice.
Based on the series of elegant pre-clinical studies, the group of Melief has developed
vaccination strategies with synthetic long peptides derived from HPV virus, which led to
markedly improved vaccine performance, resulting in the treatment of established high risk
papillomavirus-induced tumors in mice and rabbits. These studies led to the development of
vaccines for (pre-)malignant high risk HPV16-induced intraepithelial neoplasia in patients that
have proven clinical efficacy in a groundbreaking clinical study.
REFERENCES
1. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell
immunity. R. Bernards, et al. Nature 305:776, 1983.
2. Eradication of adenovirus E1-induced tumors by E1-A-specific cytotoxic T lymphocytes.
W.M. Kast, et al. Cell 59:603, 1989.
3. Specific T helper cell requirement for optimal induction of cytotoxic T lymphocytes
against major histocompatibility complex class II negative tumors. F. Ossendorp et al. J.
Exp. Med. 187:693, 1998.
4. T cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. S.P.
Schoenberger, et al. Nature 393:480, 1998.
5. Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants. Van Hall,
T et al. Nat. Med. 12:417, 2006
6. Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of
high risk HPV16 in end stage cervical cancer patients shows low toxicity and robust
immunogenicity. Kenter GG et al. Clin Cancer Res 14:169, 2008
7. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines.
Melief CJ, van der Burg SH. Nat Rev Cancer 8:351, 2008
8. Cancer immunotherapy by dendritic cells. Melief CJ. Immunity. 29:372, 2008
9. Vaccination against Human Papillomavirus 16 oncoproteins for vulvar intraepithelial
neoplasia. Kenter GG et al. N Engl J med 361:1838, 2009