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Altered CD8(+) T-cell responses when immunizing with multiepitope peptide vaccines
Steven A Rosenberg1, Richard M Sherry, Kathleen E Morton
1Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. SAR@nih.gov
Journal of Immunotherapy (Hagerstown, Md. : 1997)
|March 15, 2006
Summary
Combining cancer vaccine peptides separately enhances immune response. Mixing peptides in one emulsion reduces effectiveness, suggesting altered reactivity due to inflammation or competition.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Cancer vaccines often combine multiple peptides to improve efficacy.
- The immunological effects of combining self/tumor antigens in vaccines are not fully understood.
Purpose of the Study:
- To investigate the immunologic consequences of combining two distinct melanoma peptides (gp100 and tyrosinase) in different vaccine formulations.
- To compare the immune responses generated by separate versus combined peptide emulsions in patients at high risk for melanoma recurrence.
Main Methods:
- Two sequential clinical trials were conducted involving patients receiving either separately emulsified or co-emulsified gp100:209-217(210M) and tyrosinase:368-376(370D) peptides.
- Immune responses were assessed using cryopreserved lymphocytes evaluated via tetramer, enzyme-linked immunospot, and in vitro sensitization boost assays.
Main Results:
- Separate injection of peptides resulted in robust reactivity to gp100 but less to tyrosinase.
- Co-emulsification and single-site injection led to a significant decrease in gp100 reactivity and an enhancement of tyrosinase reactivity.
Conclusions:
- Mixing peptides in a single vaccine emulsion can negatively alter antipeptide immune responses compared to separate injections.
- Potential mechanisms for altered reactivity include localized inflammation or competitive binding to MHC molecules.