DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for aggressive NK-cell leukemia — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAggressive NK-cell leukemia maps to a 44-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for aggressive nk-cell leukemia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
NRAS proto-oncogene, GTPase (NRAS) — NRAS is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Aggressive NK-cell leukaemia is a rare malignancy with a median survival of a few months and is usually resistant to cytotoxic agents. A 2011 case report describes an 18-year-old male who obtained complete remission after two lines of combination chemotherapy, but no standard treatment has emerged from the literature. No controlled trials of any therapy for this specific disease have been reported in the abstracts provided.
The remaining abstracts concern NK-cell therapy for relapsed or refractory acute myeloid leukaemia (AML), not aggressive NK-cell leukaemia. In a 2024 phase I trial, 12 patients with refractory AML (median 5 prior therapies, median bone marrow blasts 47%) received fludarabine/cytarabine followed by six infusions of haploidentical NK cells expanded with mbIL-21 feeder cells. No toxicity or graft-versus-host disease was observed. Seven patients (58.3%) achieved complete remission with or without count recovery; median time to best response was 48 days. Five responders proceeded to a haploidentical transplant from the same donor. After a median follow-up of 52 months, 1-year overall survival for the entire group was 41.7%, 57.14% for responders, and 60% for those who received transplant. A 2018 report from two phase I trials using the same NK-cell platform in 13 patients with AML/MDS/CMML (median 4 prior therapies) reported an overall marrow remission rate of 85% (11 of 13 evaluable patients achieved <5% blasts). One patient died before day 30 from pre-existing liver toxicity, and two patients had residual CNS disease despite marrow remission.
A 2025 systematic review protocol for NK-cell therapy in relapsed/refractory AML states that the research question is structured to evaluate overall survival, serious adverse events, progression-free survival, treatment-related mortality, and response rates, but no results from that review are provided. No abstract reports NK-cell therapy being tested in aggressive NK-cell leukaemia.
What is missing: any clinical trial of NK-cell therapy specifically for aggressive NK-cell leukaemia; any prospective data on survival or response in that disease beyond single case reports; and any evidence that the promising results seen in AML would translate to this distinct NK-cell malignancy. Funding for a dedicated trial, appropriate patient stratification by KIR genotype or other biomarkers, and a trial design that accounts for the rarity and rapid progression of the disease are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Hematology · 2024 · 32 citations · open access
Results of a phase I trial with Haploidentical <scp>mbIL</scp>‐21 ex vivo expanded <scp>NK</scp> cells for patients with multiply relapsed and refractory <scp>AML</scp>
AbstractAbstract Natural killer (NK)‐cells have potent anti‐tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 patients (median age 60 years) with refractory AML (median 5 lines of prior therapy, median bone marrow blast count of 47%) with fludarabine/cytarabine followed by 6 infusions of NK‐cells expanded from haploidentical donors using K562 feeder cells expressing membrane‐bound IL21 and 4‐1BBL. Patients received 10 6 –10 7 /kg/dose. No toxicity or graft‐versus‐host disease (GVHD) was observed and MTD was not reached. Seven patients (58.3%) responded and achieved a complete remission (CR) with/without count recovery. Median time to best response was 48 days. Five responding patients proceeded to a haploidentical transplant from the same donor. After a median follow‐up of 52 months, 1‐year overall survival (OS) for the entire group was 41.7%, better for patients who responded with CR/CRi (57.14%), and for patients who responded and underwent transplantation (60%). Persistence and expansion of donor‐derived NK‐cells were identified in patients' blood, and serum IFNγ levels rose concurrently with NK cell infusions. A higher count‐functional inhibitory KIR was associated with higher likelihood of achieving CR/CRi. In conclusion, we observed a significant response to ex vivo expanded NK‐cell administration in refractory AML patients without adverse effects.
Case Reports in Hematology · 2011 · 7 citations · open access
Treatment of Aggressive NK-Cell Leukemia: A Case Report and Review of the Literature
AbstractAggressive NK-cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. The disease is usually resistant to cytotoxic agents, and no treatment has emerged as the standard of care for these patients. We report a case of an 18-year-old male who obtains complete remission following two lines of combination chemotherapy. We describe in details our regimens for induction chemotherapy and perform a review of existing literature concerning treatment of aggressive NK-cell leukemia.
Initial results of two phase I trials delivering mbIL-21 ex vivo expanded haploidentical NK cells after fludarabine/cytarabine for patients with relapsed/refractory myeloid leukemias.
Abstract7008 Background: NK cells play an important role in the control of malignancies but are ablated by high-dose chemotherapy. Thus, rapid recovery of NK cell number and function correlates with improved disease control. Haploidentical NK cells delivered after lymphodepleting chemotherapy can induce remission in patients with relapsed and/or refractory AML. Methods: We hypothesized that anti-leukemic activity could be increased without toxicity by adoptive transfer of expanded NK cells after reinduction with fludarabine, cytarabine, and G-CSF (FLAG), or mini-FLAG (4 days) for patients with low performance score. Haploidentical NK cell donors were selected by KIR ligand and/or KIR gene content. NK cells were expanded on feeder cells and cryopreserved in multiple aliquots. Patients received 3 NK-cell infusions per week for two weeks, beginning 3-10 days after chemotherapy. Response was assessed at day 30 after treatment. Parallel Phase I studies were opened using the same regimen and NK cell manufacturing platform at two centers (US and Brazil). Results: 13 patients have been treated to date, age 12-70 years (median 61y), with AML/MDS/CMML (11/1/1), having received 2-8 prior lines of therapy (median 4). 12 patients received 10^6 NK cells/kg/infusion, one received 5x10^6. One patient had no response and received other investigational therapy prior to formal disease assessment. One patient with pre-existing liver toxicity developed worsening hepatic dysfunction and died prior to day 30. Two patients achieved marrow remission but had residual CNS disease. The remaining 9 patients (69%) achieved < 5% blasts by morphology, with/without peripheral count recovery, for overall marrow remission rate of 85%. One patient progressively improved in MRD status by PCR over a 4-month period after treatment, suggesting ongoing immunologic anti-leukemic activity. Immune correlative studies will be presented at the meeting. Conclusions: Multiple infusions of cryopreserved expanded NK cells can be safely delivered after high-dose chemotherapy, with encouraging responses on this first dose level. Clinical trial information: NCT01787474.
Natural Killer Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia
AbstractThis systematic review aims to evaluate the efficacy and safety of natural killer (NK) cell therapy in patients with relapsed or refractory acute myeloid leukemia (AML). AML is the most common acute leukemia in adults and is associated with poor prognosis, especially in relapsed or refractory settings, where therapeutic options are limited and outcomes are generally unfavorable. The research question is structured according to the PICO framework: - Population (P): Individuals of any age, sex, or ethnicity diagnosed with relapsed or refractory AML. - Intervention (I): NK cell therapy used for adoptive immunotherapy, either in its native form or as a genetically modified construct (including CAR-NK). - Comparator (C): Standard treatments (such as chemotherapy, monoclonal antibodies, or stem-cell transplantation) or other drug therapies. - Outcomes (O): Primary outcomes include overall survival and serious adverse events. Secondary outcomes include progression-free survival, treatment-related mortality, complete and partial response rates, quality of life, and any adverse events.
Open Science Framework · 2025 · 0 citations · open access
Natural Killer Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia
AbstractThis systematic review aims to evaluate the efficacy and safety of natural killer (NK) cell therapy in patients with relapsed or refractory acute myeloid leukemia (AML). AML is the most common acute leukemia in adults and is associated with poor prognosis, especially in relapsed or refractory settings, where therapeutic options are limited and outcomes are generally unfavorable. The research question is structured according to the PICO framework: - Population (P): Individuals of any age, sex, or ethnicity diagnosed with relapsed or refractory AML. - Intervention (I): NK cell therapy used for adoptive immunotherapy, either in its native form or as a genetically modified construct (including CAR-NK). - Comparator (C): Standard treatments (such as chemotherapy, monoclonal antibodies, or stem-cell transplantation) or other drug therapies. - Outcomes (O): Primary outcomes include overall survival and serious adverse events. Secondary outcomes include progression-free survival, treatment-related mortality, complete and partial response rates, quality of life, and any adverse events.
Guoji shuxue ji xueyexue zazhi · 2015 · 0 citations
Research progress of cladribine in chronic lymphocytic leukemia
AbstractCladribine is a purine analogue, which is used in treatment of multiple sclerosis and hairy cell leukemia. Recently, more and more studies have shown that cladribine is a good anti-tumor choice for chronic lymphocytic leukemia (CLL). Clinical trials results show that either use alone or in combination with other drugs in patients with CLL, cladribine has shown good effect. This article focuses on the research progress of cladribine in CLL, in order to provide references for clinical medication in CLL treatment.
Key words:
Cladribine; Leukemia, lymphocytic, chronic, B-cell; Purine analog
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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