Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia
Abstract
:1. Introduction
2. Identification of Most Immunogenic Peptides from NPM1-Mutated Protein
3. Cytolytic Activity of NPM1-Mutated-Specific T Cells in Ex Vivo Assays
4. Clinical Significance of NPM1-Mutated-Specific Immune Responses in AML Patients
5. NPM1-Mutated-Specific T-Cell Responses in Allogeneic HSCT Setting
6. Exploiting Genetic Engineering of T Cells against NPM1-Mutated AML Cells
7. Immune-Checkpoint Inhibitors and Novel Therapeutic Approaches in NPM1-Mutated AML
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AML | acute myeloid leukemia |
HSCT | hematopoietic stem cell transplantation |
DLI | donor lymphocyte infusion |
NPMc | nucleophosmin1 with abnormal cytoplasmic delocalization |
CAR-T | chimeric antigen receptor-T |
TCR | T-cell receptor |
HLA | human leukocyte antigen |
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Reference | Amino Acid Sequences | Position | NPM1 Mutation Types | HLA Binding Restriction | Peptide Identification |
---|---|---|---|---|---|
Liso et al., 2008 [15] | CLAVEEVSL (9-mer) AIQDLCLAV (9-mer) | 288–296 283–291 | A/D/G/H A/D/G/H | A*02:01 A*02:01 | in silico and in vitro |
Greiner et al., 2012 [16] | AIQDLCLAV (9-mer) AIQDLCVAV (9-mer) | 283–291 283–291 | A/D/G/H C | A*02:01 A*02:01 | in silico and ex vivo |
Kuzelova et al., 2015 [18] | LAVEEVSL (8-mer) QEAIQDLCLAV (11-mer) AVEEVSLRK (9-mer) LAVEEVSLR (9-mer) QEAIQDLCL (9-mer) | 289–296 281–291 290–298 289–297 281–289 | A/D/G/H A/D/G/H A/B/C/D/G/H/J A/D/G/H A/D/G/H | C*03:03/C*03:04/B*35:03 B*37:01/B*49:01/B*40:02 A*11:01 A*68:01 B*40:01 | in silico |
Ruecker-Braun et al., 2016 [24] | AIQDLCLAV (9-mer) | 283–291 | A/D/G/H | A*02:01 | ex vivo |
Kuzelova et al., 2018 [25] | CLAVEEVSL (9-mer) DLCLAVEEV (9-mer) AIQDLCLAV (9-mer) | 288–296 286–294 283–291 | A/D/G/H A/D/G/H A/D/G/H | A*02:01 A*02:01 A*02:01 | in silico |
Forghieri et al., 2019 [19] | LAVEEVSLR (9-mer) AVEEVSLRK (9-mer) CLAVEEVSLRK (11-mer) | 289–297 290–298 288–298 | A/D/G/H A/B/C/D/G/H/J A/D/G/H | AVEEVSLRK known to have in silico binding affinity for HLA-A*02:01/A*03:01/ A*11:01/A*68:01 | ex vivo |
van der Lee et al., 2019 [20] | CLAVEEVSL (9-mer) VEEVSLRK (8-mer) AVEEVSLR (8-mer) AVEEVSLRK (9-mer) CLAVEEVSLRK (11-mer) | 288–296 291–298 290–297 290–298 288–298 | A/D/G/H A/B/C/D/G/H/J A/B/C/D/G/H/J A/B/C/D/G/H/J A/D/G/H/J | A*02:01 - - A*03:01/A*11:01 A*03:01/A*11:01 | in vitro, ex vivo and in vivo (murine model) |
Narayan et al., 2019 [21] | AVEEVSLRK (9-mer) C(Cys)LAVEEVSL (9-mer) | 290–298 288–296 | A/B/C/D/G/H/J A/D/G/H | A*03:01/A*11:01/A*31:01/ A*66:01/A*68:01/A*30:01 A*02:01 | in silico and in vitro |
Xie et al., 2020 [4] | AIQDLCLAV (9-mer) | 283–291 | A/D/G/H | A*02:01 | in vitro and in vivo (mouse model) |
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Forghieri, F.; Riva, G.; Lagreca, I.; Barozzi, P.; Bettelli, F.; Paolini, A.; Nasillo, V.; Lusenti, B.; Pioli, V.; Giusti, D.; et al. Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia. Int. J. Mol. Sci. 2021, 22, 9159. https://doi.org/10.3390/ijms22179159
Forghieri F, Riva G, Lagreca I, Barozzi P, Bettelli F, Paolini A, Nasillo V, Lusenti B, Pioli V, Giusti D, et al. Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia. International Journal of Molecular Sciences. 2021; 22(17):9159. https://doi.org/10.3390/ijms22179159
Chicago/Turabian StyleForghieri, Fabio, Giovanni Riva, Ivana Lagreca, Patrizia Barozzi, Francesca Bettelli, Ambra Paolini, Vincenzo Nasillo, Beatrice Lusenti, Valeria Pioli, Davide Giusti, and et al. 2021. "Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia" International Journal of Molecular Sciences 22, no. 17: 9159. https://doi.org/10.3390/ijms22179159