Harnessing prophylactic vaccines for targeted cancer immunotherapy by phage-guided delivery of cognate antigens to tumors
Issued Date
2026-11-01
Resource Type
ISSN
01429612
eISSN
18785905
Scopus ID
2-s2.0-105038649192
Journal Title
Biomaterials
Volume
334
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomaterials Vol.334 (2026)
Suggested Citation
Waramit S., Suwan K., Küçük A., Benjathummarak S., Cencioni M.T., Ashfield R., Gay L., Draper S.J., Hajitou A. Harnessing prophylactic vaccines for targeted cancer immunotherapy by phage-guided delivery of cognate antigens to tumors. Biomaterials Vol.334 (2026). doi:10.1016/j.biomaterials.2026.124286 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116805
Title
Harnessing prophylactic vaccines for targeted cancer immunotherapy by phage-guided delivery of cognate antigens to tumors
Corresponding Author(s)
Other Contributor(s)
Abstract
Immunotherapies hold great promise for cancer treatment, yet only a small fraction of patients respond to current approaches. We introduce a strategy that redirects pre-existing, vaccine-induced immunity to recognize and eliminate tumors. This method employs newly engineered phage-derived nanoparticles that achieve multilayered tumor specificity through ligand-mediated cell entry, transcriptional targeting, and the delivery of non-mammalian antigens absent from healthy tissues. By leveraging established immune memory, this platform enables highly specific and potent antitumor responses.We validated this concept using a malaria vaccine prototype for redirecting pathogen-specific immunity toward cancer. Specifically, we exploited the malaria epitope Pb9 (SYIPSAEKI), delivered by phage selectively to tumors in mice previously immunized with the Ad.ME-TRAP vaccine. In vitro, Pb9-expressing tumor cells were selectively recognized and destroyed by immune cells from immunized mice, accompanied by robust interferon-γ and tumor necrosis factor-α production. In vivo, systemic administration of the phage nanocarrier achieved highly selective Pb9 expression in tumors while sparing healthy organs. This tumor-restricted expression induced infiltration of antigen-specific cytotoxic T cells and natural killer cells, activation of pro-inflammatory pathways, and apoptosis within tumors. Interestingly, the combination of Ad.ME-TRAP immunization and phage-mediated Pb9 gene delivery led to complete tumor regression in a substantial proportion of animals, with durable long-term cures in over 40% of treated mice.These findings demonstrate a versatile immunotherapeutic strategy that redirects pre-existing vaccine-induced immune responses toward tumors using phage-derived, tumor-selective vectors. Beyond the malaria model, this platform offers a broadly applicable approach for repurposing preventive vaccines into safe and effective cancer immunotherapies.