Longitudinal follow-up of cellular and humoral immunity induced by recombinant adenovirus-mediated gene therapy in cancer patients

Replication-defective adenoviruses are arousing growing interest as both ge ne therapy and vaccine vectors. In a phase I clinical trial designed to eva luate the feasibility and tolerance of recombinant adenovirus (rAd)-mediate d gene transfer, we previously demonstrated that a single intratumoral inje ction of 10(9) PFU of rAd encoding the beta-galactosidase protein (Ad-beta- Gal) induced strong short-term (1-3 months) humoral, helper (Th1 type) and cytotoxic T cell responses specific for the transgene product in patients w ith advanced lung cancer. The purpose of the present study was to evaluate the persistence of long-lasting immunity to the transgene protein and in pa rallel, to assess patient immunocompetence revealed by responses to recall antigens (tetanus toroid, purified protein derivative), viral pathogens (Ep stein-Barr virus, influenza virus), and allogeneic antigens in mixed lympho cytic reactions. The beta-Gal-specific proliferative response declined rapi dly in patients with progressive disease, as did responses to the other ant igens, In contrast, a long-lasting proliferative response to beta-gal was m aintained in an immunocompetent patient in complete remission 2 years after an injection of 10(8) PFU of Ad-beta-Gal, Anti-beta-Gal humoral (IgG and I gA) responses persisted notably, as did responses to TT and poliomyelytic a ntigens, While T cell effector cytotoxic responses specific for the viral p eptides plummeted, the frequency of anti-beta-Gal CTL precursors remained p articularly high, thus attesting to major immunization, Despite the impact of both advanced disease and chemotherapy on immunocompetence, we show the long-term persistence of immunity to the transgene protein vectorized by rA d.