Formulation and evaluation of oral microparticulate ovarian cancer vaccines
Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University, College of Pharmacy and Health Sciences, Atlanta, GA 30341, USA. Vaccine
(Impact Factor: 3.62).
06/2012; 30(38):5675-81. DOI: 10.1016/j.vaccine.2012.05.073
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.
Available from: Lien Lybaert
[Show abstract] [Hide abstract]
ABSTRACT: For the development of effective anti-cancer vaccines, tumor associated antigens need to be internalized by antigen presenting cells alongside specific co-stimulatory signals. Interestingly, relative to soluble antigens, nano- and micro-particulate antigens are much better presented to CD8 T cells, a crucial step in the induction of cytotoxic T cells that can eliminate malignant cells. In this regard, a generic strategy to encapsulate cancer cell derived proteins into a particulate delivery system would be of high interest. Here we present a versatile approach to incorporate cancer cell proteins into polymeric capsules using the cells themselves as templates for layer-by-layer assembly of complimentary interacting species. After coating, the cells are killed by hypo-osmotic treatment leading to bio-hybrid capsules loaded with cell lysate. Particular focus is devoted in this work on choosing the optimal coating components and conditions to maximize cell membrane integrity during the coating process, minimize pre-mature protein release and achieve optimal encapsulation of cell lysate upon lysis of the cells. To further underline the generic nature of our approach, we demonstrate that heat shock proteins, important immune-activators, can be induced and encapsulated into the bio-hybrid capsules.
[Show abstract] [Hide abstract]
ABSTRACT: Recent advances in cancer immunotherapy have significantly improved patient life expectancy, either prophylactically or by active treatment of existing malignancies. Effective immune response by host innate and adaptive immune systems can be generated by targeting critical elements of these immune systems which include antigenpresenting cells (APC), toll-like receptors (TLR), and natural killer (NK) cells, as well as specific tumor sites which display tumor specific tumor-associated antigens. One of the major hurdles in the development of therapeutic cancer vaccines arises from the various immunosuppressive mechanisms powered by tumor cells including down-regulation of immunoresponsive antigens and cytokines. Significant strides have been made in the last decade in the identification of specific tumor receptors and tumor-specific tissue-associated antigens. Gaining a deeper level of understanding of the mechanisms by which various effectors meditate immune response and the interplay between various components of innate and adaptive immune systems has spurred research in this field. This review will discuss the innovative approaches for design and active targeted delivery of vaccines to cancers and solid tumors. Delivery systems investigated for this purpose predominantly fall into two main categories; namely biological and physical systems. Biological vaccine delivery systems include bacterial ghosts, plasmid DNA, modified dendritic cells (DCs), whole cells and tumor cell lysates, and modified viral vectors etc. Physical delivery systems include nanoparticulate and nanocolloidal systems as liposomes, polymerosomes, dendrimers, etc. The efficiency of targeting by both types of systems can be further improved by surface modification by antibodies and ligands to effectively target the appropriate tumor target.
[Show abstract] [Hide abstract]
ABSTRACT: Recent years have witnessed the development and advancement of many nonparenteral biologics and vaccines for human use. This chapter discusses various nonparenteral routes of administration. The oral route of administration is the most preferred and patient compliant method of them all. Transdermal, buccal, and pulmonary routes are also discussed. We have developed novel technologies using nanoparticles and microparticles to deliver vaccines by the oral and transdermal route of administration. These new technologies enable the formulation of vaccine particles containing vaccine antigens, without loss of their biological activity during the formulation process. Also, multiple antigens, targeting ligands and adjuvants can all be encapsulated within the same particle. When administered orally, these particles are designed to withstand the acidic environment of the stomach and are targeted to the Peyer's patches and the gut-associated mucosal immune system. Because these vaccines are particulate in nature, they are readily taken up by phagocytic antigen presenting cells (APCs), such as M cells, dendritic cells, and macrophages in the Peyer's patches of the intestines, resulting in a strong immune response and antibody production. Of particular interest is the fact that the particles release the antigen in a slow and sustained manner over a prolonged time period, intracellularly into APCs, resulting in strong mucosal and systemic immunity after oral administration, without the need for added adjuvants that are typically present in current vaccine preparations. Because no needles are required for oral vaccines, this method of vaccine delivery is inexpensive and suitable for mass vaccination in the developing world as well as for the developed world. This chapter discusses studies conducted on a wide array of vaccines, including infectious disease vaccines and cancer vaccines. This method of vaccine delivery enables the delivery of a wide spectrum of vaccines for prophylactic and therapeutic use, including oral and transdermal vaccines for cancer such as human papillomavirus, melanoma, ovarian, breast, and prostate with encouraging results. With respect to cancer therapy, a comparison is made between the conventional cancer therapy and immunotherapy. With a wide range of nanocarriers available for delivery of biologics, vaccines, and cancer therapies, nanotechnology not only has gained the well-deserved limelight but has also attracted the attention of regulatory bodies, although it presents certain challenges that must be considered before marketing such nanocarriers.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.