Vaccination against Her-2/neu, with focus on peptide-based vaccines.

Immunotherapy has been a milestone in combatting cancer, by complementing or even replacing classic treatments like surgery, chemotherapy, radiation, and anti-hormonal therapy. In 15%-30% of breast cancers, overexpression of the human epidermal growth factor receptor 2 (Her-2/neu) is associated with more aggressive tumor development. Passive immunization/immunotherapy with the recombinantly produced Her-2/neu-targeting monoclonal antibodies (mAbs) pertuzumab and trastuzumab has been shown to effectively treat breast cancer and lead to a significantly better prognosis. However, allergic and hypersensitivity reactions, cardiotoxicity, development of resistance, lack of immunological memory which results in continuous application over a long period, and cost-intensiveness are among the drawbacks associated with this treatment. Furthermore, intrinsic or acquired resistance is associated with the application of therapeutic mAbs, leading to the disease recurrence. Conversely, these drawbacks could be potentially overcome by vaccination, i.e. an active immunization/immunotherapy approach by activating the patient's own immune system to target cancer, along with inducing immunological memory. This review aims to summarize the main approaches investigated and undertaken for the production of Her-2/neu vaccine candidates, with the main focus on peptide-based vaccines and their evaluation in clinical settings.

Immunoregulatory T cell epitope peptides for the treatment of allergic disease.

Allergic diseases are type 2 inflammatory reactions with an increasing worldwide prevalence, making the search for new therapeutic options pertinent. Allergen immunotherapy is the only disease-modifying approach for allergic rhinitis, though it can result in systemic reactions. Recently, peptide immunotherapy (PIT), involving T-cell epitope peptides that bind to major histocompatibility complexes, have been developed. It is speculated that they can induce T helper cell type 2 anergy, Treg cell upregulation or immune deviation. Promising results in cat dander, honeybee venom, Japanese cedar pollen, grass pollens, ragweed and house dust mite clinical trials have shown safety, efficacy and tolerability to PIT. Hence, PIT may hold the potential to change the treatment algorithm for allergic rhinitis.

Lay abstract Allergen immunotherapy is the only disease-modifying treatment option for patients with chronic allergic rhinitis, typically featuring formulations to promote the development of immune tolerance. Although effective, the use of whole allergen has been found to promote unintended IgE crosslinking, resulting in local and systemic adverse effects. To overcome such limitations, the use of T-cell epitope peptides in allergen immunotherapy has been explored with hopeful outcomes. Compared with allergen immunotherapy, peptide immunotherapy is quicker, safer and more efficacious, making it quite promising. Although peptides for pet dander, honeybee venom, pollen and house dust mite allergies have been developed, more extensive research is necessary to prior to widespread usage.

Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8+ T Cell Epitopes.

Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for influenza peptide antigens, as shown by the induction of peptide-specific CD8+ T cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived GILGFVFTL peptide (GIL), formulated with WIV. By screening various concentrations of GIL and WIV, we found that both components contributed to the GIL-specific T cell response. Whereas co-localization of the peptide antigen and WIV adjuvant was found to be important, neither physical association between peptide and WIV nor fusogenic activity of WIV were relevant for the adjuvant effect of WIV. We furthermore show that WIV may adjuvate T cell responses to a variety of peptides, using pools of either conserved wild-type influenza peptides or chemically altered peptide ligands. This study shows the potential of WIV as an adjuvant for influenza peptides. The simple formulation process and the solid safety record of WIV make this an attractive adjuvant for T cell peptides, and may also be used for non-influenza antigens.