Generation of CD8+ T cell-mediated immunity against idiotype-negative lymphoma escapees

Abstract

We investigated the ability of CpG-oligodeoxynucleotide to generate an antitumor CD8+ T-cell immune response and to synergize with passive antibody therapy. For these studies,wegenerated an antibody against the idiotype on the A20 B-cell lymphomaline. This antibody caused the regression of established tumors, but ultimately the tumors relapsed. The escaping surface IgG-negative tumor cells were resistant to both antibody-dependent cellular cytotoxicity and signaling-induced cell death. Addition of intratumoralCpGto antibody therapy cured large established tumors and prevented the occurrence of tumor escapees. The failure of the combination therapy in mice deficient for CD8+ T cells demonstrates the critical role of CD8+ T cells in tumor eradication. When mice were inoculated with 2 tumors and treated systemically with antibody followed by intratumoral CpG in just one tumor, both tumors regressed, indicating that a systemicimmuneresponse was generated. Although antibody therapy can eliminate tumor cells bearing the target antigen, it frequently selects for antigen loss variants. However, when a poly-specific T-cell response was generated against the tumor by intratumoralCpG,even large established tumors were cured. Such an immune response can prevent the emergence of antibody selected tumor escapees and provide long-lasting tumor protection. © 2009 by The American Society of Hematology.