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ghieri, Fabio; Riva, Giovanni; Lagreca, Ivana; Barozzi, Patrizia; Bettelli, Francesca; Paolini, Ambra; Nasillo, Vincenzo; Lusenti, Beatrice; Pioli, Valeria; Giusti, Davide; Gilioli, Andrea; Colasante, Corrado; Galassi, Laura; Catellani, Hillary; Donatelli, Francesca; Talami, Annalisa; Maffei, Rossana; Martinelli, Silvia; Potenza, Leonardo; Marasca, Roberto; Tagliafico, Enrico; Manfredini, Rossella; Trenti, Tommaso; Comoli, Patrizia; Luppi, Mario
International journal of molecular sciences, 09/2021, Letnik: 22, Številka: 17Journal Article
The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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