Abstract
Nucleophosmin1 (NPM1) is one of the most frequently mutated genes in AML, is often associated with a favorable prognosis and seems to be a suitable target structure for immunotherapeutic approaches. Other groups and ours described specific immune responses of CD8-positive T cells against immunogenic epitopes derived from the mutational region of NPM1 in AML patients (pts).In this extended immunological study, we investigated immune responses against the mutational epitope of NPM1 but also against other LAA in NPM1 mut compared to NPM1 wt pts. 30 AML pts were analyzed using FACS analysis, tetramer staining and colony forming immunoassays (CFI). 15 NPM1 mut and 15 NPM1 wt pts were investigated in CFI to detect CTL mediated immune responses against leukemic progenitor/stem cells (LPC/LSC). We also added immune checkpoint inhibitors to investigate whether these immune responses could be enhanced.Against the LAA PRAME-P3, WT1 and RHAMM-R3 we detected similar frequencies of T cell responses in CFI in NPM1 mut compared to NPM1 wt pts. Antigen specific immune responses were detected in CFI by comparing growth of patient cells alone with growth by addition of antigen specific CTL and calculating colony reduction.Comparing NPM1 mut/NPM1 wt pts many had an immune response to LAA, more than 50% of the pts in both cohorts exhibited an immune response against all epitopes.In NPM1 wt pts no responses were found against the NPM1 epitope as expected, whereas NPM1 mut patients showed a high frequency of immune responses in 10/15 NPM1 mut AML pts (67%) in CFI a reduction of colonies was detected.With the addition of anti-PD1 antibody to CFI we detected an increase of immune responses. For the LAA responses were similar comparing NPM1 mut/NPM1 wt.Compared to LAA, the epitope NPM1 showed a particularly strong immune response when the antibody anti-PD1 was added. All 15 NPM1 mut pts showed an immune response with anti-PD1, with a median reduction of colonies of 47%. 7 of 15 NPM1 mut pts showed a strong immune response against LPC/LSC in CFI with more than 50% reduction of colonies.The data suggest that especially NPM1 mut patients are suitable candidates for antibody therapy with the PD1 antibody. Combination with another immunotherapy such as an NPM1 specific vaccine would be a possibility. Even though no advantage in therapy with the anti-PD1 antibody has yet been shown in the overall AML collective, this therapy could be an option for patients with NPM1 mutated AML. DisclosuresGreiner: Bristol Myers Squibb: Other: Unspecified Relationship. Schneider: AbbVie: Current Employment. Schrezenmeier: Novartis: Honoraria; Apellis: Honoraria; Sanofi: Honoraria; Alexion, AstraZeneca Rare Disease: Honoraria, Other: Travel support, Research Funding; Roche: Honoraria.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have