Topoisomerase II alpha as a universal tumor antigen: Antitumor immunity in murine tumor models and H-2Kb-restricted T cell epitope

ArticleinCancer Immunology and Immunotherapy 59(5):747-57 · November 2009with44 Reads
DOI: 10.1007/s00262-009-0795-3 · Source: PubMed
Topoisomerase II alpha (Top2alpha) is an attractive candidate to be used as a tumor antigen for cancer immunotherapy, because it is abundantly expressed in various tumors and serves as a target for a number of chemotherapeutic agents. In this study, we demonstrated the immunogenicity of Top2alpha, using dendritic cells (DC) electroporated with RNA encoding the Top2alpha C-terminus (Top2alphaCRNA/DC). Top2alphaCRNA/DC were able to demonstrate in vitro stimulation of T cells from mice that were previously vaccinated with Top2alpha-expressing tumor lysate-pulsed DC. Vaccination with Top2alphaCRNA/DC induced Top2alpha-specific T cell responses in vivo as well as antitumor effects in various murine tumor models including MC-38, B16F10, and GL26. DC pulsed with p1327 (DSDEDFSGL), defined as an epitope presented by H-2K(b), also induced Top2alpha-specific immune responses and antitumor effects. Based on these data, Top2alpha is suggested to be a universal target for cancer immunotherapy.
    • "Presence of an immunological signature can be analyzed by immuno-analytical methods against a known set of antigens, or alternatively, against a set of distinct epitopes once these have been elucidated [3][4][5]. Topoisomerase IIa (topo IIa) has been suggested as an attractive candidate tumor antigen for cancer immunother- apy [6] because of its abundant expression, presumably as a consequence of gene amplification in the tumor cells [7, 8]. This may allow a double-targeting strategy since topo IIa is addressed by a number of chemotherapeutic agents such as etoposide [9, 10] . "
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