Background: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 protein boosting. In the present study, we evaluated the immunogenicity of different HER2 ex...

PURPOSE HER2/neu, a source of immunogenic peptides, is expressed in >75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed. EXPERIMENTAL DESIGN Patients were stratified by HER2/neu expression. Low expressors (n ...

We have previously generated antihuman HER2/neu-humanized IgG3 fused to interleukin-2 (IL-2), IL-12, or granulocyte macrophage colony-stimulating factor (GM-CSF) [monofunctional fusion proteins (mono-AbFP)] or fused to IL-2 and IL-12 or IL-12 and GM-CSF [bifunctional fusion proteins (bi-AbFP)]. These AbFPs retained cytokine and antigen-binding activities. We have now further characterized the A...

Abbreviations: APC: Antigen-Presenting Cell; DCs: Dendritic Cells; RECIST: Response Evaluation Criteria in Solid Tumors; HLA: Human Leukocyte Antigen; MDSCs: Myeloid-Derived Suppressor Cells; CTLs: Cytotoxic T Cells; GM-CSF: Granulocyte-Macrophage ColonyStimulating Factor; TGF: Transforming Growth Factor; IL: Interleukin ; VEGF: Vascular Endothelial Growth Factor; PGE2: Prostaglandin E2; PD-L1:...

The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2) antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF) to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational vari...

Adoptive T-cell therapy using chimeric antigen receptor–modified T cells (CAR-T therapy) has shown dramatic efficacy in patients with circulating lymphoma. However, eradication of solid tumors with CAR-T therapy has not been reported yet to be efficacious. In solid tumors, stroma destruction, due to MHC-restricted cross-presentation of tumor antigens to T cells, may be essential. However, CAR-T...

Adoptive T-cell therapy using chimeric antigen receptor-modified T cells (CAR-T therapy) has shown dramatic efficacy in patients with circulating lymphoma. However, eradication of solid tumors with CAR-T therapy has not been reported yet to be efficacious. In solid tumors, stroma destruction, due to MHC-restricted cross-presentation of tumor antigens to T cells, may be essential. However, CAR-T...

Correlative studies of clinical for hematological malignancies have implicated that less differentiated, CD8+-dominant CAR T cell products greater antitumor activity. Here, we investigated whether the differentiation status affects their activity in preclinical models solid tumors. We explored if different activation/expansion protocols, as well co-stimulatory domains construct, influence short...