A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

• Main Authors: Milaid Granadillo, Isis Torrens, Maribel Guerra, Aileen Batte, Yordanka Soria, Osmani Mendoza, Aracelys Blanco, Alexis Musacchio, Victoria M Lugo
• Format: Article
• Language: English
• Published: Elfos Scientiae
• Series: Biotecnología Aplicada
• Subjects: proteína de fusión; e7; péptidos de penetración celular; lalf32-51; virus del papiloma humano
• Online Access: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1027-28522012000300007&lng=en&tlng=en

Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF32-51) linked to human papillomavirus 16 E7 antigen (LALF32-51-E7). In this work, we demonstrated that the immunization with LALF32-51-E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8+ T-cell response. The finding that therapeutic immunization with LALF32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8+ T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application.