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In Vivo Assay for Detection of Antigen-specific T-cell Cytolytic Function Using a Vaccination Model
Published on: November 28, 2017
A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia
Ralf G Meyer1, Cedrik M Britten, Ulrike Siepmann
1III. Medizinische Klinik, Johannes Gutenberg-Universitaet, Langenbeckstrasse 1, 55116 Mainz, Germany.
Abstract:
A significant percentage of patients with stage II melanomas suffer a relapse after surgery and therefore need the development of adjuvant therapies. In the study reported here, safety and immunological response were analyzed after vaccination in an adjuvant setting with recombinant modified vaccinia virus Ankara carrying the cDNA for human tyrosinase (MVA-hTyr). A total of 20 patients were included and vaccinated three times at 4-week intervals with 5x10(8) IU of MVA-hTyr each time. The responses to the viral vector, to known HLA class I-restricted tyrosinase peptides, and to dendritic cells transfected with tyrosinase mRNA, were investigated by ELISpot assay on both ex vivo T cells and on T cells stimulated in vitro prior to testing. The delivery of MVA-hTyr was safe and did not cause any side effects above grade 2. A strong response to the viral vector was achieved, indicated by an increase in the frequency of MVA-specific CD4+ and CD8+ T cells and an increase in virus-specific antibody titers. However, no tyrosinase-specific T-cell or antibody response was observed with MVA-hTyr in any of the vaccinated patients. Although MVA-hTyr provides a safe and effective antigen-delivery system, it does not elicit a measurable immune response to its transgene product in patients with stage II melanoma after repeated combined intradermal and subcutaneous vaccination. We presume that modification of the antigen and/or prime-boost vaccination applying different approaches to antigen delivery may be required to induce an effective tyrosinase-specific immune response.
Insights
This study found that while MVA-hTyr is a safe adjuvant therapy for melanoma patients, it did not produce a tyrosinase-specific immune response. Further research into antigen modification or prime-boost strategies is needed for effective melanoma treatment.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Stage II melanoma patients often relapse post-surgery, necessitating effective adjuvant therapies.
- Recombinant Modified Vaccinia virus Ankara carrying human tyrosinase cDNA (MVA-hTyr) was investigated as a potential adjuvant therapy.
Purpose of the Study:
- To evaluate the safety and immunological response of MVA-hTyr vaccination in an adjuvant setting for stage II melanoma.
- To assess the induction of tyrosinase-specific T-cell and antibody responses post-vaccination.
Main Methods:
- Twenty patients with stage II melanoma received three MVA-hTyr vaccinations at 4-week intervals.
- Immune responses were analyzed using ELISpot assays, measuring T-cell responses to viral vectors, tyrosinase peptides, and dendritic cells.
- Virus-specific antibody titers were also quantified.
Main Results:
- MVA-hTyr vaccination was safe, with no side effects above grade 2.
- A robust immune response to the viral vector (MVA) was observed, including increased MVA-specific CD4+ and CD8+ T cells and antibody titers.
- No tyrosinase-specific T-cell or antibody responses were detected in any vaccinated patients.
Conclusions:
- MVA-hTyr serves as a safe antigen-delivery system but failed to elicit a measurable immune response against its transgene product (tyrosinase).
- Antigen modification or alternative prime-boost vaccination strategies may be necessary to achieve an effective tyrosinase-specific immune response in melanoma patients.
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