Intra-cheek immunization as a novel vaccination route for
therapeutic vaccines of head and neck squamous cell carcinomas using plasmo
virus-like particles.
Macedo R1, Rochefort J2, Guillot-Delost M1,
Tanaka K1, Le Moignic A1, Noizat C1, Baillou C1, Mateo V1, Carpentier AF3,
Tartour E4, Bertolus C5, Bellier B6, Lescaille G2, Lemoine FM7.
1. Sorbonne Universités,
UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et
Maladies Infectieuses (CIMI-Paris) , Paris, France.
2. Sorbonne Universités,
UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et Maladies
Infectieuses (CIMI-Paris), Paris, France; Paris Diderot/Paris 07, Sorbonne
Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier
Pitié-Salpêtrière, Department of Odontology, Paris, France.
3. Université Paris 13, AP-HP, Hôpital
Avicenne, Department of Neurology, Bobigny, France.
4. Paris Descartes/Paris 05,
Sorbonne Paris Cité, INSERM U970, Paris-Cardiovascular Research Center (PARC),
AP-HP, Hôpital Européen Georges Pompidou, Service d'Immunologie Biologique ,
Paris, France.
5. Sorbonne Universités,
UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et
Maladies Infectieuses (CIMI-Paris), Paris, France; Sorbonne Universités, UPMC
Univ-Paris 06, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Department of
Maxillofacial Surgery, Paris, France.
6. Sorbonne Universités,
UPMC/Paris 06, UMR-S INSERM U959, CNRS, FRE 3632,
Immunology-Immunopathology-Immunotherapy (I3), Paris, France.
7. Sorbonne Universités,
UPMC/Paris 06, UMR-S INSERM U1135, CNRS ERL 8255, Center d'Immunologie et
Maladies Infectieuses (CIMI-Paris), Paris, France; AP-HP, Groupe Hospitalier
Pitié-Salpêtrière, Department of Biotherapies, Paris, France.
Abstract
Despite current therapy, head and
neck squamous cell carcinomas (HNSCCs) arising from various mucosal sites of
the upper aero-digestive tract frequently relapse in a loco-regional manner and
have a poor prognosis. Our objective was to validate an innovative mucosal
route of vaccination using plasmo virus-like particles (pVLPs) in a
pre-clinical orthotopic model of HNSCCs. For this purpose, we used pVLP-E7,
that are plasmid DNA encoding retroviral virus-like particles carrying a
truncated E7 oncoprotein from HPV-16 as antigen model, to vaccinate mice
bearing pre-established TC-1 tumors implanted into the buccal mucosa. pVLP-E7
were combined with clinical grade TLR agonists (Imiquimod and CpG-ODN). In this
pre-clinical orthotopic model, whose tumor microenvironment resembles to those
of human HNSCCs, different mucosal vaccination routes were tested for their
ability to elicit efficient immune and antitumoral responses. Results showed
that mucosal intra-cheek (IC) vaccinations using pVLP-E7, comparatively to
intradermic vaccinations (ID), gave rise to higher mobilization of mucosal (CD49a(+))
CD8(+) specific effector T cells in both tumor draining lymph nodes (TdLNs) and
tumor microenvironment resulting in better antitumor effects and in a long-term
protection against tumor rechallenge. In vivo CD8(+) depletion demonstrated
that antitumoral effects were fully dependent upon the presence of CD8(+) T
cells. Validation of IC mucosal vaccinations with pVLPs combined with adjuvants
using a pre-clinical orthotopic model of HNSCC provides valuable pre-clinical
data to rapidly envision the use of such therapeutic vaccines in patients with
HNSCCs, inasmuch as vaccinal components and adjuvants can be easily obtained as
clinical grade reagents.
Oncoimmunology. 2016 Jul 6;5(7):e1164363. doi:
10.1080/2162402X.2016.1164363. eCollection 2016.
Md. PhD. Rodney Macedo. Past-president del GII.
No hay comentarios:
Publicar un comentario