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Formulation and evaluation of oral microparticulate ovarian cancer vaccines
Suprita A Tawde1, Lipika Chablani, Archana Akalkotkar
1Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University, College of Pharmacy and Health Sciences, Atlanta, GA 30341, USA.
Abstract:
Ovarian cancer is the fifth most leading cause of cancer related deaths in women in the US. Customized immunotherapeutic strategies may serve as an alternative method to control the recurrence or progression of ovarian cancer and to avoid severe adverse effects of chemotherapy. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared with the use of a spray dryer. These particles were designed for oral delivery using enteric polymers such as methacrylic copolymer, Eudragit(®) FS30D and hydroxyl propyl methyl cellulose acetate succinate. These particles were targeted for uptake via microfold cell (M-cell) in Peyer's patches of small intestine using M-cell targeting ligand, Aleuria aurantia lectin. The interleukins (ILs) such as IL-2 and IL-12 were added to the vaccine formulation to further enhance the immune response. The particles obtained were of 1.58±0.62 μm size with a charge of 12.48±2.32 mV. The vaccine efficacy was evaluated by administering the particles via oral route to C57BL/6 female mice. At the end of vaccination, mice were challenged with live tumor cells. Vaccinated mice showed significant (around six-fold) retardation of tumor volume in comparison to non-vaccinated animals for 3 weeks after the tumor challenge (p<0.001). The serum IgG antibody levels were found to be elevated in case of vaccinated animals in comparison to non-vaccinated group (p<0.05). Analysis of IgG1 titers (indicative of Th2 response) and IgG2a titers (indicative of Th1 response) showed a mixed Th1 and Th2 immune response in case vaccine alone and Th2 response in case of vaccine with interleukins group. Moreover, CD8+ T-cell, CD4+ T-cell and B-cell populations in different lymphatic organs were elevated in case of vaccinated mice. Thus, whole cell lysate vaccine microparticles formulated by spray drying could trigger humoral as well as cellular immune response when administered orally. Such vaccine could potentially be an effective treatment for patients with residual tumor or high tumor-relapse probability.
Insights
This study developed an oral microparticle vaccine using ovarian cancer cells to effectively reduce tumor growth in mice. The spray-dried vaccine stimulated both cellular and humoral immune responses, offering a promising new treatment for ovarian cancer.
Area of Science:
- Immunology
- Oncology
- Materials Science
Background:
- Ovarian cancer is a leading cause of cancer deaths in women.
- Chemotherapy for ovarian cancer can cause severe side effects.
- Immunotherapy offers a potential alternative for managing ovarian cancer recurrence and progression.
Purpose of the Study:
- To develop and evaluate an oral microparticle vaccine for ovarian cancer.
- To utilize whole cell lysate from ID8 murine ovarian cancer cells.
- To enhance immune response through targeted delivery and cytokine addition.
Main Methods:
- Spray-dried microparticles were formulated using enteric polymers (Eudragit® FS30D, HPMCAS).
- Particles were targeted for microfold cell (M-cell) uptake using Aleuria aurantia lectin.
- Interleukins (IL-2, IL-12) were incorporated to boost immune response.
- Vaccine efficacy was assessed in C57BL/6 mice challenged with ID8 tumor cells.
Main Results:
- Vaccinated mice showed a significant six-fold retardation in tumor volume compared to controls (p<0.001).
- Elevated serum IgG antibody levels were observed in vaccinated mice (p<0.05).
- A mixed Th1/Th2 immune response was induced by the vaccine alone, with a Th2 bias when interleukins were added.
- Increased populations of CD8+ T-cells, CD4+ T-cells, and B-cells were found in lymphatic organs of vaccinated mice.
Conclusions:
- Spray-dried whole cell lysate microparticles effectively induce oral administration of humoral and cellular immunity.
- This oral vaccine strategy shows potential for treating residual ovarian cancer or preventing relapse.
- Targeted delivery and adjuvant incorporation enhance the immunotherapeutic potential of whole cell vaccines.
