DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for angioimmunoblastic T-cell lymphoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAngioimmunoblastic T-cell lymphoma maps to a 46-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 angioimmunoblastic t-cell lymphoma 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
ras homolog family member A (RHOA) — RHOA 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 5C4M · 1.3 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Angioimmunoblastic T-cell lymphoma is a rare subtype, making up 1% to 2% of non-Hodgkin's lymphomas. The neoplastic cells overexpress the chemokine CXCL13 and several genes characteristic of follicular helper T cells, and vascular endothelial growth factor-A is also highly expressed. Epstein-Barr virus and B cell dysregulation are implicated in the disease's pathogenesis, but their mechanistic roles remain largely unknown. Prognosis with traditional chemotherapy has been poor.
In a retrospective study of 20 patients treated between 2005 and 2010, median age was 55.9 years. All received CHOP regimen combined with other treatments such as DICE, ESHAP, Hyper-CVAD or autologous stem cell transplantation. Median survival was 20.2 months (range 5 to 69 months). Disease-free survival at 1, 2, and 3 years was 67%, 33%, and 11% respectively. Eight patients (40%) had sustained remission, surviving 63, 47, 27, 24, 24, 12, 5, and 1 months at the time of follow-up. Most patients were older with many complications during chemotherapy, resulting in easy relapse even when symptoms were alleviated early.
Novel therapeutic strategies including immunomodulation with cyclosporine and angiogenesis inhibition with bevacizumab have shown early promise. A phase 1 clinical trial (ChiCTR1800017440) is evaluating neoantigen-activated haploidentical T cell therapy for relapsed or refractory peripheral T-cell lymphoma. In 2017, one elderly patient with refractory angioimmunoblastic T-cell lymphoma treated with this approach achieved long-term complete remission. The trial aims to assess safety and tolerability.
What is still missing are larger prospective trials with consistent patient stratification, sufficient funding to move early-phase observations into randomised controlled studies, and a clearer understanding of which patients are most likely to benefit from each experimental approach. The 11% three-year disease-free survival with conventional chemotherapy underscores the need for better options, but no single agent or cell therapy has yet demonstrated reproducible efficacy across a broad patient population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Hematology · 2007 · 128 citations
Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications
AbstractPURPOSE OF REVIEW: Angioimmunoblastic T cell lymphoma is a complex lymphoproliferative disorder. While recent evidence suggests that the Epstein-Barr virus and B cell disregulation are implicated in the disease's pathogenesis, their mechanistic roles remain largely unknown. The prognosis with traditional chemotherapy has been poor, but improved understanding of the disease's pathobiology has led to several promising novel therapeutic strategies. RECENT FINDINGS: The recent finding of overexpression of the chemokine CXCL13 by the neoplastic cells of angioimmunoblastic T cell lymphoma suggests that it is derived from follicular helper T cells. In addition, gene-expression profiling has demonstrated overexpression of several genes characteristic of follicular helper T cells. Vascular endothelial growth factor-A is also highly expressed. Novel therapeutic strategies including immunomodulation with agents like cyclosporine and angiogenesis inhibition with drugs such as bevacizumab are being investigated, and show early promise in this disease. SUMMARY: Diseases such as angioimmunoblastic T cell lymphoma can help illuminate the biology of the normal immune system. Significant progress has been made in understanding the biology of angioimmunoblastic T cell lymphoma. This has paved the way for the development of new therapeutic strategies and these have shown interesting results.
Advances in Anatomic Pathology · 2002 · 48 citations
Angioimmunoblastic T-cell Lymphoma
AbstractAngioimmunoblastic T-cell lymphoma (AIL-TCL) is a rare subtype of lymphoma, making up only 1% to 2% of nonHodgkin's lymphomas; however, it accounts for a major subset of peripheral T-cell lymphomas. Angioimmunoblastic T-cell lymphoma has clinical and pathologic features that set it apart from other B- and T-cell lymphomas. More recent studies have delineated the immunophenotypic and genetic features of this unusual lymphoma, and have tentatively identified the cell of origin of this neoplasm.
Frontiers in Oncology · 2022 · 5 citations · open access
A phase I dose-escalation study of neoantigen-activated haploidentical T cell therapy for the treatment of relapsed or refractory peripheral T-cell lymphoma
AbstractPeripheral T-cell lymphoma (PTCL) is a type of highly heterogeneous non-Hodgkin lymphoma with a poor prognosis and lack of effective targeted therapies. Adoptive T-cell therapy has been successfully used in the treatment of B-cell malignancies. We first used adoptive transfer of haploidentical T cells activated by patient-specific neoantigens in vitro to treat an elderly patient with refractory angioimmunoblastic T-cell lymphoma (AITL) in 2017, and the patient achieved long-term complete remission (CR). Here we report on early results from this first-in-human phase 1 clinical trial that aims to assess the safety and tolerability of neoantigen-activated haploidentical T cell therapy (NAHTC) for relapsed/refractory PTCL. Clinical trial registration http://www.chictr.org.cn/index.aspx , identifier [ChiCTR1800017440].
Clinical analysis of 20 patients with angioimmunoblastic T-cell lymphoma
AbstractObjective To improve the diagnosis efficiency of patients with angioimmunoblastic T-cell lymphoma (AILT) by analyzing the clinical characteristics and curative effect of AILT. Methods Retrospective studies were used on clinicopathological features,immunophenotypes,treatment and survival of 20 angioimmunoblastic T-cell lymphoma patients,who were collected between January 2005 and January 2010 of Beijing Military General Hospital. Results In the 20 patients receiving chemotherapy,the median age was 55.9 years old.All of the 20 had lymph nodes and 11 of whom were accompanied with B group of symptoms,which were confirmed by lymph node biopsy and T cell antigen CD3, CD45Ro positive expression in all the patients. ALL of the patients received the CHOP regimen and combining with other treatment such as DICE,ESHAP, Hyper-CVAD or autologous hematopoietic stem cell transplantation. A follow-up by 5 to 69 months showed that median survival was 20.2 (5-69) months and 1,2,and 3-year disease free survival (DFS) were 67 ％,33 ％,and 11％ respectively.8 patients of the group (40 ％) with a sustained remission (CCS) respectively survived 63,47,27,24,24,12,5,1 months so far.Conclusion Most patients were older with many complications during chemotherapy, which resulted in easy relapse, and even the symptoms were alleviated at the early stage of the chemotherapy. IPI prognostic index is more important with long-term survival in AITL.Therefore further studies are required to improve the outcome.
Key words:
Immunoblastic lymphadenopathy; Treatment outcome; Disease-free survival
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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