Phase I/II randomized clinical trial of an oral therapeutic vaccine targeting HPV for treatment of CIN2/3
Mené sur 165 patientes atteintes d'une néoplasie cervicale intraépithéliale HPV16+ de haut grade, cet essai randomisé de phase I/II détermine la dose maximale tolérée de IGMKK16E7 (un vaccin thérapeutique à base de lactobacillus casei dispensé par voie orale et exprimant la protéine E7 de HPV16) et évalue son efficacité du point de vue de la régression histopathologique
Background: Although many HPV-targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV16 E7-expressing lacticaseibacillus-based oral vaccine. Trial design: A double-blind, placebo-controlled, randomized trial Methods: 165 patients with HPV16-positive high-grade cervical intraepithelial neoplasia (CIN2/3) were assigned to orally-administered placebo, or low-, intermediate-, or high-doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV16E7). In all four groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4 and 8 post-enrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. Results: In per-protocol analyses, histopathological regression to normal (CR) occurred in 13 (31.7%) of 41 high-dose recipients and in five (12.5%) of 40 placebo recipients (rate difference 19.2: 95% CI, 0.5-37.8). In patients positive for HPV16 only, the clinical response rate was 40.0% (12/30) in high-dose recipients and 11.5% (3/26) in recipients of placebo (rate difference 28.5: 95%CI, 4.3-50.0). There was no difference in adverse events occurred in the high-dose and placebo groups (P = 0.83). The number of HPV16E7-specific IFN-
γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P
= 0.004). The CR rates among recipients with high levels of immune response were increased in a dose-dependent manner. Conclusion: This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV16-positive CIN2/3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show anti-neoplastic effects.