Results of the First Phase I Clinical Trial of the Novel Ii-Key Hybrid Preventive HER-2/<i>neu</i>Peptide (AE37) Vaccine

Holmes, Jarrod P.; Benavides, Linda C.; Gates, Jeremy D.; Carmichael, Mark G.; Hueman, Matthew T.; Mittendorf, Elizabeth A.; Murray, James L.; Amin, Asna; Craig, Dianna; Hofe, Eric von; Ponniah, Sathibalan; Peoples, George E.

doi:10.1200/jco.2007.15.7842

Cited by 133 publications

(100 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…54 The modified MHC class II Ii-Key/HER-2/ neu(776-790) epitope hybrid peptide also has been applied as a preventive vaccine in a phase 1 clinical trial in disease-free patients with lymph node-negative breast cancer. 48 Surprisingly, the Ii-Key-modified vaccine produced enhanced immunologic responses even in the absence of an immunoadjuvant. 48 Currently, we are using the Ii-Key/HER-2/neu(776-790) hybrid peptide in a phase 1 trial of patients with HER-2/neu-positive prostate cancer.…”

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 99%

“…48 Surprisingly, the Ii-Key-modified vaccine produced enhanced immunologic responses even in the absence of an immunoadjuvant. 48 Currently, we are using the Ii-Key/HER-2/neu(776-790) hybrid peptide in a phase 1 trial of patients with HER-2/neu-positive prostate cancer. Only grade 1 toxicity has been observed in 10% of patients, whereas the majority of patients have achieved increased immunologic responses to the vaccine in vivo, measured as delayed-type hypersensitivity, and in vitro (as determined with the IFNc-based enzyme-linked immunospot assay).…”

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 99%

“…[45][46][47] All of the aforementioned studies paved the way for clinical trials of AE37 in patients with breast cancer. 48,49 Large Tumors Induce Strong Immunosuppression: The Concept of Vaccinating During the Early Stages of Tumor Formation It has been demonstrated that bulky tumors generate strong tolerizing conditions within their microenvironment that limit effective immunotherapy. Such conditions can lead to escape from immunosurveillance by allowing the cancer to become immunoresistant.…”

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 99%

See 2 more Smart Citations

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.

show abstract

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 99%

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 99%

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 99%

See 1 more Smart Citation

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, the results of the first phase I clinical trial, with the hybrid anti-HER2 AE37 peptide, have been published [31]. This vaccine is composed of the MHC-II peptide of HER2 (aa 776-779) alone (AE36) or fused on the C-terminal part with a sequence of 4 aa (LRMK) called ''li-Key'' (AE37).…”

Section: Multi-peptide Vaccinesmentioning

confidence: 99%

“…Today, protein-, peptide-, DNA-and antiidiotype (Id) antibody-based vaccines have been developed with great specificity and without toxicity [28,29]. These strategies include the alteration of the immunogenicity of naturally occurring peptides, the use of novel immunoadjuvants, CTLA-4 blockade, T-regulatory cell depletion and the use of a unique delivery system [30][31][32]. [35] have demonstrated in a preclinical model that combined administration in mice of HER2/neu-specific mAb and an HER-2/neu-expressing, GM-CSF-secreting whole tumor cell vaccine enhanced the induction of neu-specific CD8 ?…”

Section: Introductionmentioning

confidence: 99%

Anti-HER2 vaccines: new prospects for breast cancer therapy

Ladjemi

Jacot

Chardès

et al. 2010

Cancer Immunol Immunother

118

View full text Add to dashboard Cite

Each year, breast cancer accounts for more than 400,000 new cancer cases and more than 130,000 cancer deaths in Europe. Prognosis of nonmetastatic breast cancer patients is directly related to the extent of the disease, mainly nodal spreading and tumor size, and to the molecular profile, particularly HER2 over-expression. In patients with HER2-over-expressing tumors, different studies have shown cellular and/or humoral immune responses against HER2 associated with a lower tumor development at early stages of the disease. These findings have led to the hypothesis that the generation of an anti-HER2 immune response should protect patients from HER2-over-expressing tumor growth. Taken together with the clinical efficiency of trastuzumab-based anti-HER2 passive immunotherapy, these observations allowed to envisage various vaccine strategies against HER2. The induction of a stable and strong immunity by cancer vaccines is expected to lead to establishment of immune memory, thereby preventing tumor recurrence. However, an immunological tolerance against HER2 antigen exists representing a barrier to effective vaccination against this oncoprotein. As a consequence, the current challenge for vaccines is to find the best conditions to break this immunological tolerance. In this review, we will discuss the different anti-HER2 vaccine strategies currently developed; considering the strategies having reached the clinical phases as well as those still in preclinical development. The used antigen can be either composed of tumoral allogenic cells or autologous cells, or specific to HER2. It can be delivered by dendritic cells or in a DNA, peptidic or proteic form. Another area of research concerns the use of antiidiotypic antibodies mimicking HER2.

show abstract

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

et al. 2020

View full text Add to dashboard Cite

Co‐assembling vaccines composed of a lipidated HER2‐derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam3CSK4, α‐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, α‐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.

show abstract

Results of the First Phase I Clinical Trial of the Novel Ii-Key Hybrid Preventive HER-2/neuPeptide (AE37) Vaccine

Cited by 133 publications

References 36 publications

A new era in anticancer peptide vaccines

A new era in anticancer peptide vaccines

Anti-HER2 vaccines: new prospects for breast cancer therapy

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

Contact Info

Product

Resources

About