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 deli vering tumor antigens to the immune system for the initiation of antitumor immune responses. Immunization of DBA/2 mice with the P1A peptide derived f rom the P815 tumor-associated antigen P1A induced specific T-cell tolerance , resulting in progression of a regressor P815 cell line in all animals. Ho wever, immunization with a human papillomavirus type 16 L1 virus-like parti cle containing the P1A peptide in the absence of adjuvant induced a protect ive immune response in mice against a lethal tumor challenge with a progres sor 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 ch imeric virus-like particle-treated mice compared with untreated control mic e. Chimeric virus-like particles can thus be used as a universal delivery v ehicle for both tolerizing and antigenic peptides to induce a strong protec tive and therapeutic antigen-specific antitumor immune response. (C) 1999 W iley-Liss, Inc.