scholarly journals Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients

2001 ◽  
Vol 107 (4) ◽  
pp. 477-484 ◽  
Author(s):  
Keith L. Knutson ◽  
Kathy Schiffman ◽  
Mary L. Disis
2013 ◽  
Vol 134 (2) ◽  
pp. 352-366 ◽  
Author(s):  
Yusuke Tomita ◽  
Akira Yuno ◽  
Hirotake Tsukamoto ◽  
Satoru Senju ◽  
Sachiko Yoshimura ◽  
...  

Author(s):  
CV Herst ◽  
S Burkholz ◽  
J Sidney ◽  
A Sette ◽  
PE Harris ◽  
...  

AbstractThe 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.


2004 ◽  
Vol 10 (14) ◽  
pp. 4754-4760 ◽  
Author(s):  
Monique van Oijen ◽  
Adriaan Bins ◽  
Sjoerd Elias ◽  
Johan Sein ◽  
Pauline Weder ◽  
...  

2012 ◽  
Vol 56 ◽  
pp. S311
Author(s):  
J. Liu ◽  
M. Jiang ◽  
Z. Ma ◽  
J. Schlaak ◽  
M. Roggendorf ◽  
...  

Immunity ◽  
2006 ◽  
Vol 24 (5) ◽  
pp. 643-656 ◽  
Author(s):  
Yukai He ◽  
Jiying Zhang ◽  
Cara Donahue ◽  
Louis D. Falo

2002 ◽  
Vol 20 (11) ◽  
pp. 2624-2632 ◽  
Author(s):  
Mary L. Disis ◽  
Theodore A. Gooley ◽  
Kristine Rinn ◽  
Donna Davis ◽  
Michael Piepkorn ◽  
...  

PURPOSE: The HER-2/neu protein is a nonmutated tumor antigen that is overexpressed in a variety of human malignancies, including breast and ovarian cancer. Many tumor antigens, such as MAGE and gp100, are self-proteins; therefore, effective vaccine strategies must circumvent tolerance. We hypothesized that immunizing patients with subdominant peptide epitopes derived from HER-2/neu, using an adjuvant known to recruit professional antigen-presenting cells, granulocyte-macrophage colony-stimulating factor, would result in the generation of T-cell immunity specific for the HER-2/neu protein. PATIENTS AND METHODS: Sixty-four patients with HER-2/neu–overexpressing breast, ovarian, or non–small-cell lung cancers were enrolled. Vaccines were composed of peptides derived from potential T-helper epitopes of the HER-2/neu protein admixed with granulocyte-macrophage colony-stimulating factor and administered intradermally. Peripheral-blood mononuclear cells were evaluated at baseline, before vaccination, and after vaccination for antigen-specific T-cell immunity. Immunologic response data are presented on the 38 subjects who completed six vaccinations. Toxicity data are presented on all 64 patients enrolled. RESULTS: Ninety-two percent of patients developed T-cell immunity to HER-2/neu peptides (stimulation index, 2.1 to 59) and 68% to a HER-2/neu protein domain (stimulation index range, 2 to 31). Epitope spreading was observed in 84% of patients and significantly correlated with the generation of a HER-2/neu protein–specific T-cell immunity (P = .03). At 1-year follow-up, immunity to the HER-2/neu protein persisted in 38% of patients. CONCLUSION: The majority of patients with HER-2/neu–overexpressing cancers can develop immunity to both HER-2/neu peptides and protein. In addition, the generation of protein-specific immunity, after peptide immunization, was associated with epitope spreading, reflecting the initiation of an endogenous immune response. Finally, immunity can persist after active immunizations have ended.


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