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* Division of Oncology, Department of Oncology, Gastroenterology, Endocrinology, and Metabolism, St. George’s Hospital Medical School, Tooting, London, United Kingdom;
Tumor Immunology Group, Institute for Immunology, National University of Ireland, Maynooth, Ireland; and
Celgene Corp., Warren, NJ 07059
Thalidomide and its novel T cell costimulatory analogs
(immunomodulatory drugs) are currently being assessed in the treatment
of patients with advanced cancer. However, neither tumor-specific T
cell costimulation nor effective antitumor activity has been
demonstrated in vivo. In this study, we assessed the ability of an
immunomodulatory drug (CC-4047/ACTIMID) to prime a tumor-specific
immune response following tumor cell vaccination. We found that the
presence of CC-4047 during the priming phase strongly enhanced
antitumor immunity in the vaccinated group, and this correlated with
protection from subsequent live tumor challenge. Protection was
associated with tumor-specific production of IFN-
and was still
observed following a second challenge with live tumor cells 60 days
later. Furthermore, CD8+ and CD4+ splenocyte
fractions from treated groups secreted increased IFN- and IL-2 in
response to tumor cells in vitro. Coculture of naive splenocytes with
anti-CD3 mAb in the presence of CC-4047 directly costimulated T
cells and increased Th1-type cytokines. Our results are the first to
demonstrate that a costimulatory thalidomide analog can prime
protective, long-lasting, tumor-specific, Th1-type responses in vivo
and further support their ongoing clinical development as novel
anti-cancer agents.
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