Chimeric papillomavirus virus-like particles induce a murine self-antigen-specific protective and therapeutic antitumor immune response.
The use of chimeric virus-like particles represents a new strategy for delivering tumor antigens to the immune system for the initiation of antitumor immune responses. Immunization of DBA/2 mice with the P1A peptide derived from the P815 tumor-associated antigen P1A induced specific T-cell tolerance, resulting in progression of a regressor P815 cell line in all animals. However, immunization with a human papillomavirus type 16 L1 virus-like particle containing the P1A peptide in the absence of adjuvant induced a protective immune response in mice against a lethal tumor challenge with a progressor P815 tumor cell line. Additionally, we demonstrated that these chimeric virus-like particles could be used therapeutically to suppress the growth of established tumors, resulting in a significant survival advantage for chimeric virus-like particle-treated mice compared with untreated control mice. Chimeric virus-like particles can thus be used as a universal delivery vehicle for both tolerizing and antigenic peptides to induce a strong protective and therapeutic antigen-specific antitumor immune response.
Nieland
J D
JD
Cardinal Bernardin Cancer Center, Loyola University-Chicago, Maywood, Illinois 60153, USA.
Da Silva
D M
DM
Velders
M P
MP
de Visser
K E
KE
Schiller
J T
JT
Müller
M
M
Kast
W M
WM
D000818:Animals; D001483:Base Sequence; D002678:Chimera; D017931:DNA Primers; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014771:Virion / Q000276:immunology*
D017931:DNA Primers