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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 12/2008

01-12-2008 | Original Article

Immunomodulatory drugs Revlimid® (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation

Authors: Dan Zhu, Laura G. Corral, Yuedi W. Fleming, Bernd Stein

Published in: Cancer Immunology, Immunotherapy | Issue 12/2008

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Abstract

Revlimid® (Lenalidomide, CC-5013) and CC-4047 are IMiDs® immunomodulatory drugs that have been described as having immunomodulatory properties and anti-tumor activity. Here we report proapoptotic effects of CC-5013 and CC-4047 on tumor cells in a co-culture model of PBMC and tumor cells. CC-5013 and CC-4047 enhanced PBMC activity leading to tumor cell apoptosis in K562/PBMC co-culture model. We also demonstrate that the natural killer (NK) cell population of PBMC was essential in inducing K562 apoptosis. Increases of NK and natural killer T (NKT) cell populations by CC-5013 and CC-4047 was observed along with modulation of NK cell CD56 adhesion marker. In addition, our data indicate that NK activation by CC-4047 was dependent on other cell types of PBMC. We expanded the application of K562/PBMC co-culture model to other hematological and solid tumors. In Raji/PBMC co-culture model, CC-5013 and CC-4047 dose-dependently augmented tumor cell apoptosis. Pre-treatment of Raji cells with Rituximab further enhanced apoptosis induced by CC-5013 or CC-4047-treated PBMC. Moreover, CC-5013 and CC-4047 significantly increased PC-3 prostate cancer cell apoptosis in PC-3/PBMC co-culture, either as single agent or in combination with Docetaxel. Together, the results reveal that co-culture models are suitable cellular systems to assess anti-tumor activities of these compounds. Our findings support clinical evaluation of CC-5013 and CC-4047 in relapsed NHL with Rituximab and in prostate cancer with Docetaxel.
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Metadata
Title
Immunomodulatory drugs Revlimid® (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation
Authors
Dan Zhu
Laura G. Corral
Yuedi W. Fleming
Bernd Stein
Publication date
01-12-2008
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 12/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0512-7

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