Phase I trial of Lipovaxin-MM, a novel dendritic cell-targeted liposomal vaccine for malignant melanoma
| Autor: | Tessa Gargett, Paul Rolan, Joseph G. Altin, Antonio Ferrante, Michael P. Brown, Ines Atmosukarto, Katharine M. Gosling, M. Nazim Abbas, Christopher R. Parish, Jason D. Price, Andrew Ruszkiewicz |
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| Přispěvatelé: | Gargett, Tessa, Abbas, M Nazim, Rolan, Paul, Price, Jason D, Gosling, Katharine M, Ferrante, Antonio, Ruszkiewicz, Andrew, Atmosukarto, Ines IC, Altin, Joseph, Parish, Christopher R, Brown, Michael P |
| Rok vydání: | 2017 |
| Předmět: |
liposomes
0301 basic medicine Adult Male Cancer Research medicine.medical_specialty Skin Neoplasms Anemia Immunology Dose-Response Relationship Immunologic DC-SIGN Gastroenterology Cancer Vaccines 03 medical and health sciences Lethargy 0302 clinical medicine vaccine Internal medicine melanoma Immunology and Allergy Medicine Humans dendritic cells Adverse effect Melanoma Aged biology business.industry Immunogenicity clinical trial Dendritic Cells Middle Aged medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cohort Toxicity Liposomes biology.protein Female Antibody business Progressive disease |
| Zdroj: | Cancer immunology, immunotherapy : CII. 67(9) |
| ISSN: | 1432-0851 |
| Popis: | Introduction: In this phase I study using a 3 + 3 dose escalation design, the safety, dose-limiting toxicity (DLT), immunogenicity and efficacy of intravenous Lipovaxin-MM—a multi-component dendritic cell-targeted liposomal vaccine against metastatic melanoma—was investigated. Methods: Twelve subjects with metastatic cutaneous melanoma were recruited in three cohorts. Patients in Cohort A (n = 3) and Cohort B (n = 3) received three doses of 0.1 and 1 mL of Lipovaxin-MM, respectively, every 4 weeks. Patients in Cohort C (n = 6) received four doses of 3 mL vaccine weekly. Immunologic assessments of peripheral blood were made at regular intervals and included leukocyte subsets, cytokine levels, and Lipovaxin-MM-specific T-cell and antibody reactivities. Tumor responses were assessed by RECIST v1.0 at screening, then 8 weekly in Cohorts A and B and 6 weekly in Cohort C. Results: Of a total of 94 adverse events (AEs) reported in ten subjects, 43 AEs in six subjects were considered to be possibly or probably vaccine-related. Most (95%) vaccine-related AEs were grade 1 or 2, two (5%) grade 3 vaccine-related AEs of anemia and lethargy were recorded, and higher grade AEs and DLTs were not observed. No consistent evidence of vaccine-specific humoral or cellular immune responses was found in post-immunization blood samples. One patient had a partial response, two patients had stable disease, and the remaining patients had progressive disease. Conclusions: Lipovaxin-MM was well tolerated and without clinically significant toxicity. Immunogenicity of Lipovaxin-MM was not detected. Partial response and stable disease were observed in one and two patients, respectively. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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