Efficient induction of tumor antigen-specific CD8+ memory T cells by recombinant lentivectors

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(26-3)5 encoded by third-generation recombinant lentivector (rec. Iv) or as peptide admixed with a strong adjuvant. EX vivo analyses of immunized HLA-A2/H-2K(b) mice showed that rec. Iv 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. IN, 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. Iv 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.