LALF32-51-E7 therapeutic vaccine induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the lungs

Abstract

One important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported the significant antitumor effect induced by the immunization with our human papillomavirus therapeutic protein-based vaccine (LALF-E7) without adjuvant and admixed with clinically relevant adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study, we evaluated the efficacy of the above mentioned vaccine formulations in controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic clone named TC-1* and other intravenous injection site less stressful than the tail vein. We generated a lung metastasis model by injecting TC-1* cells into the retro-orbital venous sinus and this is the first study describing it. Also, this is the first study that demonstrates the efficacy of the immunization with LALF-E7 without adjuvant and admixed with VSSP or Al(OH) in controlling metastatic tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be used to test the efficacy of other immunotherapeutic strategies based on E6/E7 antigens.

Evaluation of Cell-penetrating Peptides as Mucosal Immune Enhancers for Nasal Vaccination

“…This peptide had been previously described as immune-modulator (21,23), but the present work constitutes the first report of its use by nasal route as vaccine adjuvant. Previously, based on its CPPs ability, LALF peptide had been evaluated in conjugation with E7 antigen from HPV-16 by subcutaneous route as a vaccine candidate for HPV associated malignancies treatment (23,24). In line with our results, the inclusion of LALF in the preparation favors the generation of cellular immune response in mice (23).…”

“…In favor, nonamphipathic CPPs like Tat and secondary amphipathic like Penentratin are reported as of low toxicity (45). On the other hand, LALF peptide has been showed its safety in several mice studies by subcutaneous route (20,23,24).…”

“…Currently, a second generation of LALF32-51 -derived peptides has been studied by its antitumor effect (20,22). Furthermore, based on its CPP ability, a recombinant fusion protein containing the LALF32-51 peptide conjugated to E7 antigen from HPV-16 has been evaluated, by parenteral route, as a novel vaccine candidate for the treatment of HPV related malignancies (23,24). In spite of the increasing interest on CPPs research for medical applications, mainly in cancer topics, currently there are no FDA approved CPP-conjugated drugs (25,26).…”

Evaluation of Cell-Penetrating Peptides as Mucosal Immune Enhancers for Nasal Vaccination

“…This peptide had been previously described as immune-modulator (Vallespi et al 2000 ; Granadillo et al 2011 ), but the present work constitutes the first report of its use by nasal route as vaccine adjuvant. Previously, based on its cell penetrating ability, LALF peptide had been evaluated conjugated with E7 antigen from HPV-16 by subcutaneous route as a vaccine candidate for HPV associated malignancies treatment (Granadillo et al 2011 , 2017 ). In line with our results, the inclusion of LALF in the preparation favors the generation of cellular immune response in mice (Granadillo et al 2011 ).…”

“…Currently, a second generation of LALF 32-51 -derived peptides has been studied for its antitumor effect (Guerra-Vallespi et al 2015 ; Astrada et al 2018 ). Furthermore, based on its cell penetrating ability, a recombinant fusion protein containing the LALF 32-51 peptide conjugated to E7 antigen from HPV-16 has been evaluated, by parenteral route, as a novel vaccine candidate for the treatment of HPV related malignancies (Granadillo et al 2011 , 2017 ).…”