Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells
Abstract
Immuno-oncotherapy is a highly promising therapeutic strategy that relies on the ability of cancer cells to present specific antigenic epitopes at their surfaces. Because they proliferate rapidly, cancer cells frequently accumulate genetic variants, including premature termination codons. In this study, we investigated the potential of 2,6-diaminopurine (DAP), a potent translational-readthrough-inducing molecule, to elicit an antitumor immune response. Readthrough-resulting proteins following DAP treatment can be displayed at the cell surface by the major histocompatibility complex, thus potentially enhancing immune recognition. This was demonstrated using a construct encoding FIREFLY LUCIFERASE interrupted by a UGA stop codon and fused at its C terminus with the SL8 antigenic peptide. Furthermore, in vivo exposure to DAP promotes the recruitment of immune effector cells, including T lymphocytes, macrophages, and natural killer cells, to the tumor microenvironment. These findings suggest that DAP and potentially other translational readthrough-inducing molecules hold promise as novel candidate drugs for antitumor therapy.
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BibTeX
@article{pacheco2026exploring,
title = {{Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells}},
author = {Carmen Sandoval Pacheco and Alice Leroy and Mehdi Derhourhi and Tristan Cardon and Catherine Leroy and Nathalie Jouy and Emmanuelle Com and Blandine Guevel and Roland P Bourette and Julie Carrard and Daniela Barros and Belinda Duchêne and Bénédicte Toussaint and Philippe Froguel and Nicolas Jonckheere and Thierry Chassat and Isabelle Van Seuningen and Régis Lavigne and Charles Pineau and Philippe Pierre and Fabrice Soncin and Michel Salzet and Amélie Bonnefond and Fabrice Lejeune},
journal = {Molecular Therapy},
year = {2026},
month = nov,
doi = {10.1016/j.ymthe.2025.09.024},
url = {https://hal.science/hal-05849952v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells
AU - Carmen Sandoval Pacheco
AU - Alice Leroy
AU - Mehdi Derhourhi
AU - Tristan Cardon
AU - Catherine Leroy
AU - Nathalie Jouy
AU - Emmanuelle Com
AU - Blandine Guevel
AU - Roland P Bourette
AU - Julie Carrard
AU - Daniela Barros
AU - Belinda Duchêne
AU - Bénédicte Toussaint
AU - Philippe Froguel
AU - Nicolas Jonckheere
AU - Thierry Chassat
AU - Isabelle Van Seuningen
AU - Régis Lavigne
AU - Charles Pineau
AU - Philippe Pierre
AU - Fabrice Soncin
AU - Michel Salzet
AU - Amélie Bonnefond
AU - Fabrice Lejeune
PY - 2026
DA - 2026/11/03
JO - Molecular Therapy
DO - 10.1016/j.ymthe.2025.09.024
UR - https://hal.science/hal-05849952v1
AB - Immuno-oncotherapy is a highly promising therapeutic strategy that relies on the ability of cancer cells to present specific antigenic epitopes at their surfaces. Because they proliferate rapidly, cancer cells frequently accumulate genetic variants, including premature termination codons. In this study, we investigated the potential of 2,6-diaminopurine (DAP), a potent translational-readthrough-inducing molecule, to elicit an antitumor immune response. Readthrough-resulting proteins following DAP treatment can be displayed at the cell surface by the major histocompatibility complex, thus potentially enhancing immune recognition. This was demonstrated using a construct encoding FIREFLY LUCIFERASE interrupted by a UGA stop codon and fused at its C terminus with the SL8 antigenic peptide. Furthermore, in vivo exposure to DAP promotes the recruitment of immune effector cells, including T lymphocytes, macrophages, and natural killer cells, to the tumor microenvironment. These findings suggest that DAP and potentially other translational readthrough-inducing molecules hold promise as novel candidate drugs for antitumor therapy.
SN - 1525-0016
SN - 1525-0024
ER -