Airway administration of a highly versatile peptide-based liposomal construct for local and distant antitumoral vaccination

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• 作者：Zahra Kakhi^a ; Benoî ; t Frisch^a ; Line Bourel-Bonnet^a ; Joseph Hemmerlé ; ^b ; Franç ; oise Pons^a ; ^{pons@unistra.fr" class="auth_mail" title="E-mail the corresponding author} ; Bé ; atrice Heurtault^a ; ^{bheurtault@unistra.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACK ; ammonium-chloride-potassium ; APC ; antigen-presenting cell ; BALF ; bronchoalveolar lavage fluids ; CTL ; cytotoxic T-lymphocyte ; CV ; coefficient of variation ; DPG-Mal ; dipalmitoyl glycerol-maleimide ; ELISA ; enzyme-linked immunosorbent assay ; ELISpot ; enzyme-linked immunosorbent spot ; Eq. ; equivalent ; i.d. ; intradermic ; IFN-γ ; interferon-gamma ; IL ; interleukin ; i.m. ; intramuscular ; i.p. ; intraperitoneal ; i.v. ; intravenous ; KC ; keratinocyte chemoattractant ; MALT ; mucosa-associated lymphoid tissue
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：30 December 2015
• 年：2015
• 卷：496
• 期：2
• 页码：1047-1056
• 全文大小：923 K

文摘

With the discovery of tumor-associated antigens such as ErbB2, vaccination is considered as a promising strategy to prevent the development of cancer or treat the existing disease. Among routes of immunization, the respiratory route provides the opportunity to develop non-invasive approach for vaccine delivery. In the current study, this administration route was used in order to investigate the potency of a highly versatile di-epitopic liposomal construct to exhibit local or distant antitumoral efficiency after prophylactic or therapeutic vaccination in mice. Well-characterized liposomes, containing the ErbB2 (p63–71) TCD8⁺ and HA (p307–319) TCD4⁺ peptide epitopes and the Pam₂CAG adjuvant, were formulated and administered into the airway of naïve BALB/c mice. The nanoparticle vaccine candidate induced local and specific systemic immune response, as measured by immune cell infiltration and chemokine and cytokine production in BALF or lung tissue, and by spleen T-cell activation ex vivo, respectively. This potent immune response resulted in an efficient antitumor activity against both lung and solid s.c. tumors. Interestingly, the antitumor efficacy was observed after both prophylactic and therapeutic vaccinations, which are the most judicious ones to fight cancer. Our data showed an undeniable interest of liposomal peptide-based vaccines in antitumor vaccination by the respiratory route, opening new perspectives for cancer treatment.