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Efficient Induction of Tumor Antigen–Specific CD8⁺ Memory T Cells by Recombinant Lentivectors

Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland

Requests for reprints: Frédéric Lévy, Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41-21-692-5998; Fax: 41-21-692-5995; E-mail: Frederic.Levy{at}isrec.unil.ch.

The success of active cancer immunotherapy entails a robust induction of tumor-reactive effector and memory CD8⁺ T cells. We compared the in vivo immunogenicity of the melanoma-associated antigen Melan-A_26-35 encoded by third-generation recombinant lentivector (rec. lv) or as peptide admixed with a strong adjuvant. Ex vivo analyses of immunized HLA-A2/H-2K^b mice showed that rec. lv triggered a stronger anti-Melan-A CD8⁺ T-cell response than peptide vaccine. Importantly, the majority of anti-Melan-A T cells elicited by rec. lv expressed the memory marker CD127 at the peak of the primary response. In those mice, memory T cells were detectable several months after priming and could be activated by recall peptide vaccination. These results show that immunization with rec. lv induces not only a strong antigen-specific CD8⁺ T-cell response but also a long-lasting T-cell memory against a bona fide tumor-associated antigen. (Cancer Res 2006; 66(2): 1155-60)

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