Research Terms
Currently, there are limited therapies available to treat people with refractory cancers like acute myeloid leukemia (AML), non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). To solve this problem, University of Florida scientists discovered that blood vessels are sanctuary sites for leukemia. The scientists demonstrated that leukemia cells within the vascular niche are resistant to traditional chemotherapy like cytarabine. To solve the problem of refractory, vascular-associated leukemia, they developed a high throughput screening (HTS) assay to screen 31 million compounds that selectively killed AML cells embedded within an endovascular niche. A hit compound was discovered and was further optimized by deconvolution. The compound is cytotoxic to cell lines and primary specimens of AML, NSCLC and TNBC patients. The compound is non-toxic to normal hematopoietic cells, endothelial cells, and fibroblastic stromal cells. Extensive proteomic testing shows the compound binding a splicing factor. In vivo AML xenografting shows that the compound significantly remits leukemia compared to cytarabine control. New genetic knock-down models of AML, NSCLC, and TNBC have been created to dissect the molecular mechanisms of depleting the target. The investigators seek commercial entities to develop this compound into a new class of drugs for the treatment of cancer.
Small molecules for treating cancer
After a unique HTS of leukemia cells embedded within an endovascular niche, a hit compound was identified and optimized by deconvolution. Additionally, the hit compound is toxic to leukemia stem cells and non-toxic to normal hematopoietic and stromal cells. Proteomic testing identified a splicing factor as the compound’s target. The compound has drug-like properties and in vivo efficacy better than chemotherapy control. New genetic knock-down models were also created to further elucidate the mechanism of action.
This antiviral agent stimulates patients’ own immune system against malignant cells to cause disease regression. Cancer remains one of the most costly and challenging diseases to treat, particularly in hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). While older patients often see remission rates of 40 to 60%, only 5 to 15% will have prolonged remission or cures. Patients with relapse or refractory AML have poor long-term survival, with a median overall survival of 6 months. In MDS, only 40 to 50% of patients achieve remission with a hypomethylating agent (HMA), and nearly all patients will suffer from disease relapse, with a survival time of 5.6 months. Standard treatment options often rely on intensive chemotherapy, stem cell transplantation, or targeted biologics, many of which are poorly tolerated by older patients or those with relapsed or refractory disease. As a result, patients frequently experience limited survival, high toxicity, and few viable therapeutic alternatives.
The economic burden associated with these cancers is substantial. The global oncology therapeutics market exceeded $200 billion in 2024 and is projected to grow steadily as cancer incidence rises worldwide. Within this space, hematologic malignancies represent a multi-billion dollar segment, driven by high treatment costs, prolonged care, and repeated lines of therapy. Despite this investment, outcomes for relapsed AML and MDS remain poor, creating strong demand for more effective, lower-toxicity, and cost-efficient treatments. At the same time, immuno-oncology has become one of the fastest-growing areas in cancer therapeutics, with the global cancer immunotherapy market valued at over $120 billion in 2024 and expected to grow at a double-digit compound annual growth rate. However, many current immunotherapies are expensive, require complex manufacturing, or fail to benefit significant subsets of patients, limiting their broad clinical impact.
Researchers at the University of Florida have repurposed abacavir, a widely used FDA-approved drug, as a precision cancer immunotherapy for addressing both the clinical and economic limitations of existing therapies. Rather than developing a new molecular entity, this strategy leverages a known drug with an established safety profile to selectively activate anti-tumor immune responses in genetically defined patient populations. By combining drug repurposing with precision immunotherapy, the antiviral agent offers the potential to significantly reduce development cost, accelerate clinical translation, and expand treatment options for patients with high unmet need cancers such as AML and MDS.
A precision immunotherapy method for treating AML and MDS by administering abacavir to patients expressing specific HLA alleles either as a standalone therapy or in combination with existing cancer treatments
This antiviral agent is based on the interaction between abacavir and specific human leukocyte antigen (HLA) molecules, particularly HLA B*57:01. Abacavir, an FDA-approved drug for HIV treatment, is known to bind selectively to certain HLA proteins, altering how antigens are presented on the surface of cells. This altered presentation triggers activation of CD8? cytotoxic T cells, a key component of the immune system responsible for killing abnormal cells. In standard clinical use, abacavir-induced immune activation is avoided due to the risk of hypersensitivity reactions. In contrast, this invention strategically repurposes and controls this immune response to promote immune-mediated destruction of cancer cells. By leveraging the drug–HLA interaction, the technology enables a precision immunotherapy approach that targets genetically defined patient populations while minimizing unintended immune effects.
The invention further defines cancer-specific dosing regimens and treatment schedules that differ from antiviral use and are optimized for oncology applications such as AML and MDS. Patients are selected based on HLA genotype, enabling predictable therapeutic response and compatibility with companion diagnostic testing. This approach may be used as a standalone therapy or combined with existing cancer treatments to enhance overall clinical effectiveness.
