Immunological Evaluation of Co-Assembling a Lipidated Peptide Antigen and Lipophilic Adjuvants: Self-Adjuvanting Anti-Breast-Cancer Vaccine Candidates

被引:23
作者
Aiga, Taku [1 ]
Manabe, Yoshiyuki [1 ,2 ]
Ito, Keita [1 ,2 ]
Chang, Tsung-Che [1 ]
Kabayama, Kazuya [1 ,2 ]
Ohshima, Shino [3 ]
Kametani, Yoshie [3 ]
Miura, Ayane [1 ]
Furukawa, Hiroto [4 ]
Inaba, Hiroshi [4 ]
Matsuura, Kazunori [4 ]
Fukase, Koichi [1 ,2 ]
机构
[1] Osaka Univ, Grad Sch Sci, Dept Chem, 1-1 Machikaneyama, Toyonaka, Osaka 5600043, Japan
[2] Osaka Univ, Project Res Ctr Fundamental Sci, Grad Sch Sci, Core Med & Sci Collaborat Res & Educ, 1-1 Machikaneyama, Toyonaka, Osaka 5600043, Japan
[3] Tokai Univ, Sch Med, Isehara, Kanagawa 2591193, Japan
[4] Tottori Univ, Ctr Res Green Sustainable Chem, Grad Sch Engn, Dept Chem & Biotechnol, 4-101 Koyama Minami, Tottori 6808552, Japan
关键词
adjuvants; antigens; cancer; peptides; self-assembly; ROBUST IMMUNE-RESPONSES; CLINICAL-TRIAL; ALPHA-GALACTOSYLCERAMIDES; LIPOPEPTIDE ADJUVANTS; MITOGENIC PRINCIPLE; CONJUGATE VACCINES; CELL-ACTIVATION; RECOGNITION; AGONIST; MUC1;
D O I
10.1002/anie.202007999
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Co-assembling vaccines composed of a lipidated HER2-derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam(3)CSK(4), alpha-GalCer, or lipid A 506, were evaluated as breast cancer vaccine candidates. This vaccine design was aimed to inherit both antigen multivalency and antigen-specific immunostimulation properties, observed in reported self-adjuvanting vaccine candidates, by using self-assembly and adjuvant-conjugated antigens. Under vaccination concentrations, respective lipophilic adjuvants underwent co-assembly with lipidated CH401, which boosted the anti-CH401 IgG and IgM production. In particular, alpha-GalCer was responsible for the most significant immune activation. Therefore, the newly developed vaccine design enabled the optimization of adjuvants against the antigenic CH401 peptide in a simple preparatory manner. Overall, the co-assembling vaccine design opens the door for efficient and practical self-adjuvanting vaccine development.
引用
收藏
页码:17705 / 17711
页数:7
相关论文
共 74 条
[1]   Linked Toll-Like Receptor Triagonists Stimulate Distinct, Combination-Dependent Innate Immune Responses [J].
Albin, Tyler J. ;
Tom, Janine K. ;
Manna, Saikat ;
Gilkes, Adrienne P. ;
Stetkevich, Samuel A. ;
Katz, Benjamin B. ;
Supnet, Medalyn ;
Felgner, Jiin ;
Jain, Aarti ;
Nakajima, Rie ;
Jasinskas, Algis ;
Zlotnik, Albert ;
Pearlman, Eric ;
Davies, D. Huw ;
Felgner, Phillip L. ;
Burkhardt, Amanda M. ;
Esser-Kahn, Aaron P. .
ACS CENTRAL SCIENCE, 2019, 5 (07) :1137-1145
[2]   NKT cell-dependent glycolipid-peptide vaccines with potent anti-tumour activity [J].
Anderson, Regan J. ;
Compton, Benjamin J. ;
Tang, Ching-wen ;
Authier-Hall, Astrid ;
Hayman, Colin M. ;
Swinerd, Gene W. ;
Kowalczyk, Renata ;
Harris, Paul ;
Brimble, Margaret A. ;
Larsen, David S. ;
Gasser, Olivier ;
Weinkove, Robert ;
Hermans, Ian F. ;
Painter, Gavin F. .
CHEMICAL SCIENCE, 2015, 6 (09) :5120-5127
[3]   Roles of NKT cells in cancer immunotherapy [J].
Bae, Eun-Ah ;
Seo, Hyungseok ;
Kim, Il-Kyu ;
Jeon, Insu ;
Kang, Chang-Yuil .
ARCHIVES OF PHARMACAL RESEARCH, 2019, 42 (07) :543-548
[4]   Branched and linear lipopeptide vaccines have different effects on primary CD4+ and CD8+ T-cell activation but induce similar tumor-protective memory CD8+ T-cell responses [J].
Baz, Adriana ;
Buttigieg, Kathy ;
Zeng, Weiguang ;
Rizkalla, Michael ;
Jackson, David C. ;
Groves, Penny ;
Kelso, Anne .
VACCINE, 2008, 26 (21) :2570-2579
[5]   Lipopeptide vaccines - yesterday, today, and tomorrow [J].
BenMohamed, L ;
Wechsler, SL ;
Nesburn, AB .
LANCET INFECTIOUS DISEASES, 2002, 2 (07) :425-431
[6]   THE MITOGENIC PRINCIPLE OF ESCHERICHIA-COLI LIPOPROTEIN - B-LYMPHOCYTE MITOGENICITY OF THE SYNTHETIC ANALOG PALMITOYL-TETRAPEPTIDE (PAM-SER-SER-ASN-ALA) [J].
BESSLER, WG ;
COX, M ;
WIESMULLER, KH ;
JUNG, G .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 121 (01) :55-61
[7]   Fully Synthetic Self-Adjuvanting Thioether-Conjugated GlycopeptideLipopeptide Antitumor Vaccines for the Induction of Complement-Dependent Cytotoxicity against Tumor Cells [J].
Cai, Hui ;
Sun, Zhan-Yi ;
Huang, Zhi-Hua ;
Shi, Lei ;
Zhao, Yu-Fen ;
Kunz, Horst ;
Li, Yan-Mei .
CHEMISTRY-A EUROPEAN JOURNAL, 2013, 19 (06) :1962-1970
[8]   Results of the First Phase 1 Clinical Trial of the HER-2/neu Peptide (GP2) Vaccine in Disease-Free Breast Cancer Patients [J].
Carmichael, Mark G. ;
Benavides, Linda C. ;
Holmes, Jarrod P. ;
Gates, Jeremy D. ;
Mittendorf, Elizabeth A. ;
Ponniah, Sathibalan ;
Peoples, George E. .
CANCER, 2010, 116 (02) :292-301
[9]  
Cavallari M, 2014, NAT CHEM BIOL, V10, P950, DOI [10.1038/NCHEMBIO.1650, 10.1038/nchembio.1650]
[10]  
Chang T. C., 2018, ANGEW CHEM, V130, P8351