Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen

Dendritic cells (DC) are potent antigen-presenting cells that play a critic al role in the initiation of cellular immune responses. Using a BALB/c syng eneic colon carcinoma cell line expressing a model tumor antigen beta -gala ctosidase (beta gal), we previously reported (Song et al, J Exp Med 1997; 1 86. 1247-1256) that immunization of mice with a single injection of DCs gen etically modified with an adenovirus vector expressing beta gal confers pot ent protection against a lethal intravenous tumor challenge, as well as sup pression of preestablished lung tumors, resulting in a significant survival advantage. In the present study, we have addressed the question: how long does the memory of tumor antigen-specific immunity persists after DC primin g in vivo using this genetically modified DC-based cancer vaccination strat egy? To accomplish this, two groups of mice were evaluated: (1) mice surviv ing >400 days following protection from an initial intravenous tumor challe nge after immunization with DC genetically modified to express beta gal; an d (2) mice surviving >300 days that had previously demonstrated regression of pre-established lung tumors after treatment with DC immunization. By ana lyzing the antigen-specific cytotoxic T lymphocyte response and challenging these long-term survival mice with a second subcutaneous tumor administrat ion, the data demonstrate that a single administration of DC genetically mo dified to express a model antigen induces long-lasting, antigen-specific an titumor immunity in both naive and tumor-bearing hosts, observations that h ave important implications in the development of genetically modified DC-ba sed antitumor vaccination strategies.