Induction of CD8 T‐cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20‐mer NY‐ESO‐1f (NY‐ESO‐1 91‐110) peptide

Abstract

Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.The NY-ESO-1 antigen was originally identified in esophageal cancer by serological expression cloning (SEREX) using autologous patient serum. 1,2 NY-ESO-1 expression is observed in a wide range of human malignancies, but the expression is restricted to germ cells in the testes in normal adult tissues. [1][2][3][4] Therefore, NY-ESO-1 has emerged as a prototype of a class of cancer/testis (CT) antigens. 5 The efficacy of the NY-ESO-1 antigen as a cancer vaccine has been studied extensively using various preparations, e.g., peptide, protein or DNA, etc. of the antigen with various adjuvants. [6][7][8][9][10][11][12][13][14] These studies established the safety of the NY-ESO-1 vaccine and demonstrated its immunogenicity.In a phase I clinical trial, we immunized cancer patients with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 whole protein (CHP-NY-ESO-1) and showed that the vaccine had potent capacity to induce the NY-ESO-1 antibody in vaccinated patients. 13,14 The most dominant serological antigenic epitope was NY-ESO-1 91-108. The CHP-NY-ESO-1 vaccine also elicited CD4 and CD8 T-cell responses in immunized patients. 14 Analysis of T cell responses against overlapping peptides (OLPs) spanning the NY-ESO-1 molecule revealed that two dominant NY-ESO-1 regions, regions II (73-114) and III (121-144), were recognized by either CD4 or CD8 T-cells in most patients irrespective of their HLA type. Essentially similar findings were obtained by studies using other preparations of NY-ESO-1 protein vaccine. 11,12,15

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

“…From the 114 studies, full-text was unavailable for one study 13 , 2 studies were duplicates published under different titles 14,15 , one study only described the study design 16 and 6 studies did not report safety, tolerability and/or toxicity results 7,[17][18][19][20][21] . These together with 11 case reports [22][23][24][25][26][27][28][29][30][31][32] and 2 letters to the editor were excluded 33,34 . Ultimately, a total of 91 studies were included in the systemic safety review.…”

Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 c259T Cells in Synovial Sarcoma

“…Like other translocation-driven cancers, synovial sarcoma demonstrates a relative paucity of nSSMs (12), which likely explains its unresponsiveness to checkpoint blockade (13). In contrast, 70% to 80% of synovial sarcomas express NY-ESO-1 (14)(15)(16), an immunogenic cancer testis antigen that has been targeted using vaccines (17)(18)(19)(20)(21) and adoptive transfer of T cells engineered to express NY-ESO-1 c259 , an affinity-enhanced T-cell receptor (TCR) targeting NY-ESO-1/LAGE1a (22)(23)(24)(25).…”

Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope

“…17,37 In that regard, numerous publications have reported on the immunogenicity of NY-ESO-1, and in particular of the protein region 87-111. 17,18 , 20,38 Mandic et al previously reported on the characterization of a CD4 T-cell clone recognizing the epitope 87-101 presented by HLA-DR7 transfected cells, 17 By fine mapping of specific CD4 C T-cell responses in our cohort of HLA-DR7…”