Multipeptide vaccination in cancer patients.
Since the identification of tumor associated antigens (TAA) in different tumor histotypes, many vaccination strategies have been investigated, including peptide-based vaccines. Results from the first decade of clinical experimentation, though demonstrating the feasibility and the good toxicity profile of this approach, provided evidence of clinical activity only in a minority of patients, despite inducing immunization in up to 50% of them. In this review, we discuss the different approaches recently developed in order to induce stronger peptide-induced immune-mediated tumor growth control, possibly translating into improved clinical response rates, with specific focus on multipeptide-based anti-cancer vaccines. This strategy offers many advantages, such as the possibility of bypassing tumor heterogeneity and selection of antigen (Ag)-negative clones escaping peptide-specific immune responses, or combining HLA class I- and class II-restricted epitopes, thus eliciting both CD4- and CD8-mediated immune recognition. Notably, advances in Ag discovery technologies permit further optimization of peptide selection, in terms of identification of tumor-specific and unique TAA as well as Ags derived from different tumor microenvironment cell components. With the ultimate goal of combining peptide selection with patient-specific immunogenic profile, peptide based anti-cancer vaccines remain a promising treatment for cancer patients, as attested by of pre-clinical and clinical studies.
Pilla
Lorenzo
L
Immuno-biotherapy of Melanoma and Solid Tumors, San Raffaele Foundation Scientific Institute, Milan, Italy.
Rivoltini
Licia
L
Patuzzo
Roberto
R
Marrari
Andrea
A
Valdagni
Riccardo
R
Parmiani
G
G
D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000939:Epitopes / Q000737:chemistry; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000639:trends; D008545:Melanoma / Q000628:therapy; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000628:therapy; D012878:Skin Neoplasms / Q000628:therapy; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use*
D019496:Cancer Vaccines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D022223:Vaccines, Subunit