Granadillo M, Torrens I, Guerra M, Batte A, Soria Y, Mendoza O, Blanco A, Musacchio A, Lugo VM

Language: English
References: 6
Page: 194-197
PDF size: 199.38 Kb.

ABSTRACT

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 (LALF_32-51) linked to human papillomavirus 16 E7 antigen (LALF_32-51-E7). In this work, we demonstrated that the immunization with LALF_32-51-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 LALF_32-51 or E7 alone, or an admixture of LALF_32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF_32-51 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.

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