Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors

Abstract

We have shown that Listeria-based cancer vaccines inhibit the growth of transplanted tumors in a transgenic mouse model of immune tolerance where HPV-16 E7 is expressed in the thyroid gland. In this study we determine whether these vaccines are able to inhibit autochthonous tumor growth in this animal model. Mice treated with Listeria vaccines expressing E7 had significantly smaller thyroid tumors than did mice treated with controls and possessed higher numbers of antigen-specific CD8+ T cells within the spleens, tumors, and peripheral blood. This study shows that Listeria-based vaccines are able to slow autochthonous tumor growth and break immunological tolerance.

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

“…On the other hand, several bacterial HPV vaccines targeting E6 and E7 have been developed. Sewell et al showed that in an HPV 16 transfected mouse model, mice that were vaccinated with Listeria based anti E7 vaccine experienced a substantial reduction in tumor size (65). Interestingly, an ongoing clinical study evaluates the efficacy of neoadjuvant listeriabased HPV vaccine ADX11-001 in patients with HPV+ HNSCC stage I-IV undergoing robot-assisted surgery (NCT02002182).…”

Harnessing Listeria monocytogenes to target tumors

“…Lm-LLO-E7, and a similar recombinant vaccine that expresses E7 fused to the listerial virulence factor ActA were found to delay the appearance of thyroid tumors and slow their growth in the E6/E7 transgenic mouse. 51 Further evidence that Listeria based tumor antigen expression systems can break tolerance was provided by Bruhn et al who showed that vaccination with Listeria, expressing TAA tyrosinase-related protein (TRP-2) induced prophylactic and therapeutic protection of mice from challenge by B16 melanoma tumors expressing TRP-2.…”

A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers

“…Live recombinant vaccines that express HPV E7 or E6 proteins have proven generally to stimulate strong CD4þ and CD8þ T cell responses in mice model (Lin et al, 2010). Various bacterial vectors have been explored in HPV therapeutic vaccines including Listeria monocytogenes (Sewell et al, 2008), Lactobacillus lactis (BermudezHumaran et al, 2005), Lactobacillus plantarum (CortesPerez et al, 2005) and Salmonella (Krul et al, 1996). Moreover, some effective properties make viral vectors a induces IFN-g production at before (A), 3 weeks (B) and 6 weeks (C) after challenge.…”