Erbb2 DNA vaccine combined with Treg cell deletion enhances antibody response and reveals latent low-avidity T cells. Potential and limits of its therapeutic efficacy

estroy after use. Rat (r) Erbb2 transgenic BALB-neuT mice genetically predestined to develop multiple invasive carcinomas allow an assessment of the potential of a vaccine against the stages of cancer progression. Due to Erbb2 expression in the thymus and its over-expression in the mammary gland, CD8 + T cell clones reacting at high avidity with dominant Erbb2 epitopes are deleted in these mice. In BALB-neuT mice with diffuse and invasive in situ lesions and almost palpable carcinomas, a temporary Treg cells depletion combined with anti-rErbb2 vaccine markedly enhanced the antirErbb2 antibody response and allowed the expansion of latent pools of low-avidity CD8 + T cells bearing T cell receptors repertoire reacting with the rErbb2 dominant peptide. This combination of a higher antibody response and activation of a low-avidity cytotoxic response persistently blocked tumor progression at stages in which the vaccine alone was ineffective. However, when diffuse and invasive microscopic cancers become almost palpable this combination was no longer able to secure a significant extension of mice survival.