• Overian Cancer Microparticulate Vaccines: Effect of Routes of Administration

      Tawde, Suprita Ashok; College of Pharmacy
      Ovarian cancer is the most lethal gynecological cancer in the U.S. First-line treatment for advanced cancer involves surgery followed by chemotherapy. However, cancer relapses within short periods of time even after treatment. Therefore, alternative approach of immunotherapy is being investigated. We studied vaccination with microparticles containing the ovarian cancer antigens can prevent/retard ovarian cancer growth. Oral and transdermal routes are attractive modes of immunization because of their ease of administration and patient compliance. In this project we explored microparticulate system to target immune cells and to initiate response against ovarian cancer antigens via oral, subcutaneous and transdermal delivery. We selected a murine cell line which correlates closely to human cell line in terms of antigen expression and tumor formulation. We prepared the antigenic lysate and characterized it for the presence of a known antigen. We loaded micro-particulate delivery systems with the lysate. These particles were formulated with desired physical properties suitable for particle uptake and for anticipated immune response. In the present study, we demonstrate the efficacy of vaccine formulations wuth was evaluated in vivo in mouse tumor model, using the murine ovarian cancer cell line as a solid tumor model via oral, transdermal, subcutaneous and via combination of oral and transdermal routes. The tumor volumes upon challenge with live tumor cells were monitored in vaccinated animals and control animals. Humoral and cellular immune response in all the animals were monitored to determine the immune mechanism initiated by the vaccine microparticles. Encouraging results from these prophylactic particulate overian cancer studies provided the basis to design therapeutic study to mimic the real-time scenario where patients with residual tumors after a surgery are the recipients of such vaccine therapy. Further, to elucidate the role of M-cells in particle uptake once administered orally, we induced M-cells in murine models and administered microparticles loaded with a model antigen with and without immune adjuvant. The immune response generated via these vaccine particles in mice models with induced M-cells was compared to control animals, to determine whether particles followed the M-cell pathway for their uptake in order to trigger immune cells.