Research we fund

Innovations in gene engineering have made it possible to reprogram immune cells to attack specific targets on cancer cells, allowing the first adoptive cellular immunotherapies, known as CAR T cells, to be approved by the FDA for the treatment B lymphoblastic leukemia. A similar approach is currently under development for AML, but in contrast to B-ALL, there is no leukemia-specific target which would be amenable to targeting by immune cells without incurring severe adverse effects. Here, we aim to modify normal bone marrow stem cells used for allogeneic transplantation to make them resistant to CAR-T cells, thus enabling targeting proteins essential for tumor survival without the risk of severe toxicity on the healthy tissue counterpart.

This proposal examines the use of CD19-directed chimeric antigen receptor (CD19-CAR) T cell immunotherapy to treat adults aged 55 years or older who have acute lymphoblastic leukemia (ALL) that is in remission following induction therapy (i.e., “first remission”). In this clinical trial, we will infuse the CD19-CAR T cells early in the treatment sequence, which may prevent the leukemia from returning without additional therapy. This clinical trial aims to give us a better understanding of CD19-CAR T cell safety and activity when given during first remission, with the goal of improving the very poor outcomes of older adults with ALL.

On the basis that T-cell acute lymphoblastic leukemia (T-ALL) cells overexpress IL-7 receptor (IL7R), which promotes chemotherapy resistance and relapse, we developed IL7R-targeted chimeric antigen receptor (CAR) T cells with low- and high-affinity single-chain variable fragments (scFvs). Following extensive investigation, we established the antitumor efficacy of low-affinity IL7R CAR against T-ALL cells in vitro, in vivo and against patients’ T-ALL blasts using their own T cells transduced with IL7R CAR. With data establishing tumor specificity and antitumor efficacy, and a novel manufacturing method of ‘natural selection’ to seamlessly manufacture a large number of IL7R CAR T cells from patients with T-ALL, we are now proceeding with Investigational New Drug studies to initiate a phase I clinical trial in 2025 Q4.

We aim to determine if rigorous assessment of quality of life (QOL) can help with treatment decisions for hairy cell leukemia (HCL). We will first analyze a robust HCL patient database to understand QOL trajectories among patients before they need initial treatment or relapse, as well as among specific subgroups such as those who are younger (75), and those who or working. We will then then utilize a patient-driven consensus process to determine which QOL instruments most accurately reflect experiences when facing treatment or re-treatment. Finally, we will engage 30 HCL patients nearing treatment or re-treatment, measure QOL, and provide results for discussion with providers, measuring feasibility and preliminary impact of this approach.

We will test the first fully oral, chemotherapy-free drug combination that simultaneously blocks two different key survival mechanisms in hairy cell leukemia. First, it blocks the genetic cause of the disease, i.e. the BRAF mutant gene, using the BRAF inhibitor drug vemurafenib. Second, it deprives leukemic cells of their intrinsic ability of resisting natural cell death (apoptosis) by blocking the apoptosis inhibitor BCL2 with the drug venetoclax. We have already tested in patients either drug alone, and found that both have some efficacy and each one has its distinct limitations. By combining them for a short period of time, we aim to develop an overall more effective treatment. Importantly, this approach is designed with patients in mind to also preserve their quality of life and lessen treatment-related social disruption.

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.

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 Allotera (formerly Wugen) to "Support Clinical Development of Sofi-Cel in Relapsed/Refractory T-ALL/T-LBL."

Allotera is a clinical-stage biotechnology company focused on developing next-generation, allogeneic CAR-T cell therapies for cancer. Allotera'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. Allotera 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 (NCT06994676) is the first clinical trial for Crossbow and the T-Bolt™ platform . 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 AML, high-risk MDS, CMML and CML.

CBX-663 is the second candidate developed through Crossbow’s T-Bolt™ platform. CBX-663 targets telomerase reverse transcriptase (TERT), a protein that drives tumor growth and is overexpressed in approximately 90% of all cancers.

The Phase 1, open-label, dose-escalation TelOscope-001 study (NCT07779798) is evaluating the safety, tolerability, and clinical activity of CBX-663 in patients with relapsed or refractory myeloid malignancies, advanced solid tumors, or recurrent or progressive glioblastoma multiforme.  

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.