Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors
| Autor: | Robert Wesolowski, Maryam B. Lustberg, Jay Overholser, Bhuvaneswari Ramaswamy, Christina Wu, Tanios Bekaii-Saab, Pravin T. P. Kaumaya, Lai Wei, Daniel H. Ahn, Amir Mortazavi, Jeffrey M. Fowler |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Maximum Tolerated Dose Receptor ErbB-2 medicine.medical_treatment Oleic Acids Article Cohort Studies 03 medical and health sciences 0302 clinical medicine Adjuvants Immunologic Trastuzumab Neoplasms Internal medicine Tumor Cells Cultured medicine Humans Mannitol Aged Cell Proliferation Aged 80 and over B-Lymphocytes business.industry Immunogenicity Immunotherapy Middle Aged medicine.disease Vaccination Regimen Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis Vaccines Subunit Epitopes B-Lymphocyte Female Immunization Pertuzumab business Adjuvant Progressive disease medicine.drug |
| Zdroj: | Clin Cancer Res |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-18-3997 |
| Popis: | Purpose: This first-in-human phase I study (NCT 01417546) evaluated the safety profile, optimal immunologic/biological dose (OID/OBD), and immunogenicity of the combination of two peptide B-cell epitope vaccines engineered to represent the trastuzumab- and pertuzumab-binding sites. Although trastuzumab and pertuzumab have been approved for clinical use, patients often develop resistance to these therapies. We have advanced a new paradigm in immunotherapy that focuses on humoral responses based on conformational B-cell epitope vaccines. Patients and Methods: The vaccine is comprised of two chimeric HER-2 B-cell peptide vaccines incorporating a “promiscuous T-cell epitope.” Patients were immunized with the vaccine constructs emulsified with nor-muramyl-dipeptide adjuvant in a water-in-oil Montanide ISA 720VG vehicle. Eligible patients with metastatic and/or recurrent solid tumors received three inoculations every 3 weeks. Results: Forty-nine patients with a median of 4 prior lines of chemotherapy received at least 1 vaccination. Twenty-eight patients completed the 3 vaccination regimens. Six patients received 1 six-month boost after the regimen, and one patient received 7 six-month boosts. No serious adverse reactions or dose-limiting toxicities were observed. The vaccine was well tolerated with dose level 2 as the recommended phase II dose. The most common related toxicity in all patients was injection-site reactions (24%). Two patients had a partial response, 14 had stable disease, and 19 had progressive disease. Conclusions: The study vaccine is safe, exhibits antitumor activity, and shows preliminary indication that peptide vaccination may avoid therapeutic resistance and offer a promising alternative to monoclonal antibody therapies. |
| Databáze: | OpenAIRE |
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