Research Terms
This nanoparticle vaccine targets the slow-cycling, treatment-resistant, cancer stem cells to improve efficiency of anti-cancer drugs, thereby improving disease prognosis. Despite major developments in the field of anti-cancer therapies, tumor recurrence and metastasis after chemotherapy is still the major cause of cancer patient mortality. Although current RNA-lipid nanoparticle (NP) vaccines have shown promising results, they still remain encumbered by profound intra-tumoral and systemic immunosuppression. Because of the heterogeneity of cancer epitopes, a major challenge in the field of vaccine development is determining the best target. Studies carried out by our researchers at the University of Florida have demonstrated that recurrences in gliomas can be attributed to the subset of slowly dividing cells, resistant to conventional anti-cancer therapies. These slowly dividing cells exhibit enhanced tumorigenicity and infiltrative propensity. Hence, clinical strategies targeting this specific population of cancer cells holds great potential in improving therapeutic efficiency of drugs.
To address this issue of cancer recurrence, our scientists have developed a universal RNA-NP vaccine engineered with RNAs for epitopes specific to slow-cycling tumor cells, as well as a personalized RNA-NP vaccine engineered from RNA extracted from patient’s tumor biopsy. These vaccines are able to activate T-cell recognition of slow-cycling tumor-initiating stem cells mediating sustained anti-tumor activity in the mouse model of glioma.
Nanoparticle vaccine for either personalized or universal treatment of cancer
This therapeutic platform demonstrates the use of two different nanoparticle (NP) vaccines (personalized and universal) engineered with RNA derived from a specific subpopulation of slow-cycling, tumor-initiating stem cells. These immunomodulating vaccines are able to elicit T-cell response against slow-cycling, tumor-initiating cancer stem cells, leading to sustained anti-tumor activity. Researchers found that systemic administration of this vaccine primes the peripheral and intra-tumoral microenvironments for response to immunotherapy. These RNA-NPs localize to heart, lung, bone marrow, spleen, liver, kidney and subcutaneous/intracranial tumors. In immunologically resistant tumor models (i.e. B16F0, B16-F10, Lewis lung carcinoma) resistant to immune checkpoint inhibitors, these RNA-NPs activate the preponderance of systemic and intra-tumoral antigen presenting cells (characterized by co-expression of PD-L1 and CD86) for induction of anti-tumor immunity. Altogether, this therapeutic platform delivers specific sets of tumor RNA antigens purified from slow-cycling cancer stem cells to create personalized or universal vaccines.
This cancer vaccine activates antigen-presenting cells and induces anti-tumor immune system activity for the treatment of diffuse intrinsic pontine gliomas (DIPG). DIPG tumors originate in the pons, an area of the brainstem controlling vital body functions such as breathing and heart rate. DIPG is the main type of brain tumor causing death in children, and it comprises 10-20 percent of all pediatric brain tumor cases. The widely spread nature and location of these tumors prevent early diagnosis, which greatly limits treatment options. Surgical resection is not possible due to the tumors’ location, and chemotherapy has not been successful at treating DIPG. Radiation therapy has been able to shrink tumor size, but this effect is typically short-lived and does not cure patients. Diagnosing patients with DIPG usually occurs between the ages of 5 and 9, and their median survival rate is 10-11 months.
Researchers at the University of Florida have developed a vaccine that treats DIPG by driving anti-tumor immunity. The global RNA therapeutics and vaccine market is expected to surpass $800 million by the end of 2029. This RNA vaccine delivers liposomal nanoparticles by intravenous injection that activate specific antigen-presenting cells to increase immunogenicity against DIPG. Improved survival rates in animal models have demonstrated the vaccine’s success.
An off-the-shelf vaccine for the treatment of diffuse intrinsic pontine glioma (DIPG)
This RNA vaccine targets a homogenously expressed diffuse intrinsic pontine glioma (DIPG) tumor antigen, allowing for widespread use without the need for customized treatment. The RNA renewably encodes specific DIPG antigens to continuously vaccinate the patient, increasing central memory T-cell levels for sustained anti-tumor immunity. A liposomal nanoparticle delivers the vaccine to prevent RNA degradation.
This cancer vaccine stimulates the production of antibodies against a cell surface antigen common to both melanoma and osteosarcoma tumors and works in conjunction with chemotherapy. Melanoma is an aggressive form of skin cancer that’s highly metastatic at later stages. Osteosarcoma is the most common form of bone cancer and also is highly metastatic. Beyond chemotherapy, which is only moderately effective and has numerous side effects, physicians may employ immunotherapies such as adoptive T-cell therapies to treat these and other cancers. Because T-cell therapies involve delivering live whole cells, administration must wait until after chemotherapy. Since cancers are typically able to evade destruction by the immune system, cancer vaccines aim to encourage the immune system to attack cancer cells by eliciting an immune response against tumor-specific antigens. However, developing effective cancer vaccines has proven challenging due to the difficulty of eliciting a robust and consistent immune response against "self" antigens. The global market for cancer vaccines is estimated to have over a 12% growth rate, reaching almost $12 billion by 2026.
Researchers at the University of Florida have developed a vaccine for melanoma and osteosarcoma cancers based on the tumor-specific antigen disialoganglioside (GD3). The nano-liposome composition of the vaccine enhances its stability and stimulates a robust response by both the innate and adaptive arms of the immune system, even during the administration of chemotherapy.
Cancer vaccine that targets GD3 antigen to treat melanoma and osteosarcoma
This nanolipo-GD3 vaccine enhances the production of antibodies that target tumor cells expressing the disialoganglioside (GD3) antigen. Both melanoma and osteosarcoma tumor cells express the antigen, thus potentially resulting in a single vaccine that effectively targets both of these common and hard to treat cancers. This cancer vaccine is an “off the shelf” immunotherapy, that is effective without requiring customization for each patient. The vaccine is able to stimulate an immune response even during a chemotherapy treatment regimen. UF’s scientists have demonstrated in dogs with melanoma that the vaccine improved survival by two- to three-fold with a course of four intradermal injections of the vaccine. Humans and dogs with melanoma have shared histopathologic and genetic features, especially in the oral mucosal forms, making dogs an ideal large animal translational model for this study. In the case of osteosarcoma, when the vaccine is given with standard of care the median survival is 552 days compared to 292-310 days for standard of care alone.
DEPARTMENT OF NEUROSURGERY PO BOX 100265 PO BOX 100265 GAINESVILLE, FL 32610-0265