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Demarcated thresholds of tumor-specific CD8 T cells elicited by MCMV-based vaccine vectors provide robust correlates of protection.
Beyranvand Nejad, Elham Ratts, Robert B Panagioti, Eleni Meyer, Christine Oduro, Jennifer D Früh, Klaus van der Burg, Sjoerd H Arens, Ramon
Beyranvand Nejad, Elham
Ratts, Robert B
Panagioti, Eleni
Meyer, Christine
Oduro, Jennifer D
Früh, Klaus
van der Burg, Sjoerd H
Arens, Ramon
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2019-01-31
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Abstract
The capacity of cytomegalovirus (CMV) to elicit long-lasting strong T cell responses, and the ability to engineer the genome of this DNA virus positions CMV-based vaccine vectors highly suitable as a cancer vaccine platform. Defined immune thresholds for tumor protection and the factors affecting such thresholds have not well been investigated in cancer immunotherapy. We here determined using CMV as a vaccine platform whether critical thresholds of vaccine-specific T cell responses can be established that relate to tumor protection, and which factors control such thresholds. We generated CMV-based vaccine vectors expressing the E7 epitope and tested these in preclinical models of HPV16-induced cancer. Vaccination was applied via different doses and routes (intraperitoneal (IP), subcutaneous (SC) and intranasal (IN)). The magnitude, kinetics and phenotype of the circulating tumor-specific CD8 Immunization with CMV-based vaccines via the IP or SC route eliciting vaccine-induced CD8 This study highlight the effectiveness of CMV-based vaccine vectors, and shows that demarcated thresholds of vaccine-specific T cells could be defined that correlate to tumor protection. Together, these results may hold importance for cancer vaccine development to achieve high efficacy in vaccine recipients.
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J Immunother Cancer. 2019 Jan 31;7(1):25. doi: 10.1186/s40425-019-0500-9
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Article
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en
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2051-1426
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Attribution-NonCommercial-ShareAlike 4.0 International