Research we fund

Most of the Hairy Cell Leukemia variant patients do not respond to conventional therapies. They develop resistance to the chemotherapy drugs and we will investigate why this happens. Our data shows that a protein called BAFF is playing a key role in providing additional survival advantages to these patient cells to resist therapies. We will develop new treatment methods by targeting this protein in order to make these patients sensitive to therapy and to improve clinical outcome.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by clonal proliferation of abnormal myeloid precursors and poor prognosis despite advances in treatment. Recent work using Rapid Extracellular Antigen Profiling (REAP) has shown that autoantibody responses can correlate with disease outcomes and immune dysregulation in cancer.

We will leverage a large, clinically annotated AML biobank containing patient demographics, genetic mutations, treatment history, and outcomes to identify autoantibody  patterns associated with survival and clinical phenotypes.

CD7-CAR T cells with CD7-PEBL represents an innovative technology that enables the production of CAR T cells able to escape the fratricide for the treatment of relapsed/refractory T-ALL. At Bambino Gesù Children’s Hospital, in collaboration with Prof. Campana (Singapore), we have tested the safety of these CAR T cells in children/young adults with relapsed/refractory T-ALL obtaining promising results, in terms of both safety and efficacy. We now aim to activate a Phase 2 multicenter study to further explore the efficacy of this approach.

In February 2026, TAP made an equity investment in Wugen to "Support Clinical Development of Sofi-Cel in Relapsed/Refractory T-ALL/T-LBL."

Wugen is a clinical-stage biotechnology company focused on developing next-generation, allogeneic CAR-T cell therapies for cancer. Wugen’s proprietary gene-editing platform is designed to overcome key limitations of first-generation cell therapies, enabling scalable, off-the-shelf treatments with biologics-like cost of goods margins.

Soficabtagene Geleucel (Sofi-cel) is an allogeneic, off-the-shelf, CD7-targeted CAR-T cell therapy engineered to overcome the technological challenges of harnessing CAR-T cells to treat T-cell cancers. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T cell receptor alpha constant (TRAC) genes, thereby preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host disease (GvHD). Sofi-cel is manufactured using healthy donor-derived T cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting. Sofi-cel is currently being evaluated in a global pivotal clinical trial for relapsed or refractory T-ALL/T-LBL (NCT06514794).

Sofi-cel has received Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. FDA and Priority Medicines (PRIME) Scheme designation in the European Union for the treatment of relapsed or refractory T-ALL/T-LBL. RMAT and PRIME designations provide increased agency support to expedite the development and review of promising therapies for patients in need.

In September 2025, TAP made an equity investment in Crossbow Therapeutics to "Support Clinical Development of CBX-250 in Relapsed/Refractory AML, MDS and CMML."

Crossbow Therapeutics is a biotechnology company determined to improve the lives of people with cancer by unlocking the therapeutic potential of T-cell receptor (TCR)-mimetic antibodies. The company’s T-Bolt™ therapies are next-generation, easily assembled immunotherapies directed with high precision at previously unreachable cancer cell targets.

CBX-250 is the first candidate developed through Crossbow’s T-Bolt™ platform, a portfolio of novel TCE molecules that uniquely target peptide-loaded human leukocyte antigen (pHLA) complexes on tumor cells, using antibodies that mimic T-cell receptors (TCR-mimetics). Specifically, CBX-250 targets a cathepsin G pHLA complex, abundantly expressed on leukemic cells, but not normal cells. 

The Phase 1, open-label, dose-escalation CROSSCHECK-001 study is the first clinical trial for Crossbow and the T-Bolt™ platform (NCT06994676). The study is evaluating the safety, tolerability, and preliminary clinical activity of CBX-250 in patients aged 12 years and older with relapsed or refractory acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (HR- MDS), and chronic myelomonocytic leukemia (CMML).

Follicular lymphomas (FL) are a diverse group of B-cell cancers with unpredictable clinical outcomes. Current treatment strategies are hindered by the heterogeneity of FL, which stems from differences in genetic mutations, immune microenvironments (MEs), and stepwise progression, as well as a lack of preclinical models that accurately reflect the human disease. The "ERADICATE Follicular Lymphoma" (E-FL) Consortium brings together world-leading experts in artificial intelligence (AI), therapeutic modeling, experimental therapeutics, and immunology to address these challenges. Preliminary studies indicate that FL arises from distinct clonal precursor cells that create unique immunological niches, evolve through diverse trajectories, and exhibit specific biological dependencies. The E-FL Consortium’s integrated projects aim to identify and characterize these CPCs, their MEs, and the genetic and immune factors driving FL progression. Four projects will investigate the origins of FL CPCs, the role of clonal evolution in tumor heterogeneity, novel therapeutic targets, and mechanisms of immunotherapy resistance. Supported by two scientific hubs for data integration and biomarker development, the consortium will generate actionable insights to guide precision therapies and early intervention strategies. Deliverables include publicly available FL datasets, predictive biomarkers, novel experimental models, and therapeutic tools to improve outcomes and quality of life for FL patients.

The combination of hypomethylating agents (HMA) and venetoclax (Ven) is a standard of care to treat acute myeloid leukemia (AML). However, HMA+Ven is not curative, and most patients will ultimately relapse without effective treatment options available thereafter. Our institution has discovered a novel AML target and pioneered the development of a best-in-class chimeric antigen receptor T cell therapy (CART64) for patients who have relapsed after HMA+Ven treatment. We now propose to demonstrate safety and effectiveness of CART64 in a phase 1, first-in-human, clinical trial in patients with advanced AML and high-risk myelodysplastic syndromes (HR-MDS).

While many immunotherapy studies in children with leukemia focus on establishing early responses, this project studies what life is like, and what health and social challenges are experienced, in those who survive their leukemia long-term. Using data from over 700 patients across many hospitals, we aim to identify factors that predict long-term remission, side effects, and quality of life. We will also collect patient-reported experiences to better understand survivorship and improve care. 

This grant proposal aims to uncover inherited resilience to clonal hematopoiesis (CH) and myeloid malignancies (MyMs). Our pilot work has identified a regulatory variant that significantly protects from CH/MyM through downregulation of MSI2 levels in human hematopoietic stem cells (HSCs). We seek to perform rigorous mechanistic studies to identify an RNA network that regulates human HSCs and is modulated through genetic variation to protect them from CH/MyMs.

Mutations in the RNA splicing factor gene SRSF2 occur in 25% of patients with MDS, 50% of patients with chronic myelomonocytic leukemia (CMML), and 25% of AML patients over the age of 65.

We recently developed a cell therapy directed against abnormal proteins on the surface of cells expressing mutant SRSF2. This proposal aims to improve this new form of immunotherapy and extend its benefit to the largest number of patients with myeloid blood cancers.