Formulation and In Vivo Evaluation of Particulate Breast Cancer Vaccine

Abstract

Purpose: This research work concentrates on formulating two particulate breast cancer vaccines, which are further evaluated in vivo using two murine breast cancer models. As breast cancer continues to be the most fatal cancer among women throughout the world, there is an immediate need to develop a vaccine to combat it. Considering the potential of particulate delivery vehicles to impart robust systemic as well as mucosal immune response, they have been explored not only against infectious diseases but also against cancer.

In this project we take advantage of these micron sized particulate delivery vehicles to target immune cells and to initiate immune response against breast cancer antigens, Also, these particles have been fabricated in such a manner that they can be administered via patient-compliant routes of administration including oral and intraepidermal delivery.

Research methodology: We have explored various polymers to optimize two enteric protected particulate delivery systems with desired physical properties making them susceptible to particle uptake and there by leading to anticipated immune response. These particles have been evaluated carefully for their size, charge, surface morphology, release profiles, cyto-toxicity and particle uptake by various in vitro studies. Further the particle uptake of vaccines by the M (microfold) cells in the Peyer's patches of the small intestine when given orally is studied extensively along with characterization of microchannels created to deliver the microparticulate vaccine. Also, the vaccine efficacy was evaluated in vivo in female mice model using the two marine breast cancer cell lines which mimic the progression of breast cancer as seen in humans, The vaccine was administered via oral, intraepidermal and sub-cutaneous routes resulting in immune response against the breast cancer antigens used in the vaccine.

Results and Conclusion: The vaccinated animal had sugnificantly smaller tumor volumes than the control animals, as seen after challenging the animal upon termination of treatment. Immune responses in all the animals were monitored to gauge the role of humoral and cellular immunity in generating protection by several in vitro and ex vivo studies. Promising results from these two prophylactic particulate breast cancer vaccine studies have advanced our laboratory to explore a therapeutic breast cancer vaccine. These particulate delivery systems possess the potential of entering the clinical trials and mimicking the real-time situation where patient's own tumor cells extracted after a surgery can serve as the source of antigens for an individualized particulate vaccine.