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Peptide vaccine

About: Peptide vaccine is a research topic. Over the lifetime, 1750 publications have been published within this topic receiving 45160 citations.


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TL;DR: A synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma and, on the basis of immunologic assays, 91% of patients could be successfully immunized with this peptide.
Abstract: The cloning of the genes encoding cancer antigens has opened new possibilities for the treatment of patients with cancer. In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma. On the basis of immunologic assays, 91% of patients could be successfully immunized with this synthetic peptide, and 13 of 31 patients (42%) receiving the peptide vaccine plus IL-2 had objective cancer responses, and four additional patients had mixed or minor responses. Synthetic peptide vaccines based on the genes encoding cancer antigens hold promise for the development of novel cancer immunotherapies.

1,842 citations

Journal ArticleDOI
TL;DR: The multiple antigen peptide system provided a general, but chemically unambiguous, approach for the preparation of carrier-bound antigens of predetermined and reproducible structure and might be suitable for generating vaccines.
Abstract: A convenient and versatile approach to the direct synthesis of a peptide-antigen matrix by the solid-phase method is described. The approach is called the multiple antigen peptide system (MAP) and it utilizes a simple scaffolding of a low number of sequential levels (n) of a trifunctional amino acid as the core matrix and 2n peptide antigens to form a macromolecule with a high density of peptide antigens of final Mr 10,000. The MAP model chosen for study was an octa-branching MAP consisting of a core matrix made up of three levels of lysine and eight amino terminals for anchoring peptide antigens. The MAP, containing both the core matrix and peptides of 9-16 amino acids, was prepared in a single synthesis by the solid-phase method. Six different MAPs elicited specific antibodies in rabbits and mice, of which five produced antibodies that reacted with their corresponding native proteins. In rabbits, the sera had a considerably higher titer of antibodies than sera prepared from the same peptides anchored covalently to keyhole limpet hemocyanin as carrier. Thus, the MAP provided a general, but chemically unambiguous, approach for the preparation of carrier-bound antigens of predetermined and reproducible structure and might be suitable for generating vaccines.

1,351 citations

Journal ArticleDOI
TL;DR: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine andInterleukin-2 than with interleuk in-2 alone.
Abstract: Background Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. Methods We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end p...

801 citations

Journal ArticleDOI
TL;DR: Findings indicate that the CD40–CD40 ligand pair can act as a 'switch', determining whether naive peripheral CTLs are primed or tolerized, and support the clinical use of CD40-stimulating agents as components of anti-cancer vaccines.
Abstract: The outcome of antigen recognition by naive CD8+ cytotoxic T lymphocytes (CTLs) in the periphery is orchestrated by CD4+ T-helper cells, and can either lead to priming or tolerization. The presence of T-helper cells favors the induction of CTL immunity, whereas the absence of T-helper cells can result in CTL tolerance. The action of T helper cells in CTL priming is mediated by CD40–CD40 ligand interactions. We demonstrate here that triggering of CD40 in vivo can considerably enhance the efficacy of peptide-based anti-tumor vaccines. The combination of a tolerogenic peptide vaccine containing a minimal essential CTL epitope with an activating antibody against CD40 converts tolerization into strong CTL priming. Moreover, CD40 ligation can provide an already protective tumor-specific peptide vaccine with the capacity to induce therapeutic CTL immunity in tumor-bearing mice. These findings indicate that the CD40–CD40 ligand pair can act as a 'switch', determining whether naive peripheral CTLs are primed or tolerized, and support the clinical use of CD40-stimulating agents as components of anti-cancer vaccines.

525 citations

Journal ArticleDOI
TL;DR: It is demonstrated that both HLA-A2-restricted breast and ovarian tumor-specific cytotoxic T lymphocytes recognize shared antigenic peptides derived from the oncogene product of HER2/neu, which is overexpressed in 30-40% of all breast and Ovarian cancers.
Abstract: The identification of antigenic peptides presented on the tumor cell surface by HLA class I molecules and recognized by tumor-specific cytotoxic T lymphocytes may lead to a peptide vaccine capable of inducing protective cellular immunity. We demonstrate that both HLA-A2-restricted breast and ovarian tumor-specific cytotoxic T lymphocytes recognize shared antigenic peptides. At least one of these peptides is derived from the oncogene product of HER2/neu, which is overexpressed in 30-40% of all breast and ovarian cancers. T cells sensitized against this nine-amino acid sequence demonstrate significant recognition of HLA-A2+, HER2/neu+ tumors. Since 50% of the tumor-cell population is HLA-A2+ and many different tumors express HER2/neu, this peptide may be widely recognized and have many clinical applications.

508 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023136
2022111
2021119
2020156
201987
2018101