Oral microparticulate vaccine for melanoma using M-cell targeting

Abstract

Cancer vaccines are limited in their use, because of their inability to mount a robust anti-tumor immune response. Thus, targeting M-cells in the small intestine, which are responsible for entry of many pathogens, will be an attractive way to elicit a strong immune response toward particulate antigens. Therefore, in the present investigation, we demonstrated that efficient oral vaccination against melanoma antigens could be accomplished by incorporating the antigens in an albumin-based microparticle with a ligand AAL (Aleuria aurantia lectin) targeted specifically to M-cells. The oral microparticulate vaccine effectively protected the mice from subcutaneous challenge with tumor cells in prophylactic settings. The animals were vaccinated with antigen microparticles having a size range of around 1-1.25 µm where one prime and four booster doses were administered every 14 days over 10 weeks of duration, followed by challenge with live tumor cells, which showed complete tumor protection after oral vaccination. With the inclusion of ligand in the microparticles, we observed significantly higher IgG titers (1565 μg/mL) as compared to the microparticle formulations without AAL (872 μg/mL). This data suggests that ligand loaded microparticles may have the potential to target antigens to M-cells for an efficient oral vaccination.

Trends in Nonparenteral Delivery of Biologics, Vaccines and Cancer Therapies

“…The mucosal route of entry and initiation of primary immune response is well established where pathogens and other invasive microbes enter the host system via regions in the small intestine. Bernadette et al 128 described a study wherein they formulated a novel prophylactic oral microparticulate vaccine composed of whole cell lysate for melanoma using the spray-drying technique. Surface morphology of microparticles evaluated by scanning electron microscopy (SEM) showed that the particles had a spherical surface with a size distribution of around 1 to 2 mm ( Figure 5.8).…”

Microneedle and mucosal delivery of influenza vaccines

“…M cells particularly adhere to microparticles and actively transport them into Peyer’s patches in intestines. Therefore, ligands targeting M cells, incorporated into microparticles would be a promising approach to increase the efficacy of uptake of oral vaccines in intestines [103,152]. Challenges in developing oral vaccination in humans include the requirement for higher doses of vaccines and lower efficacy in inducing systemic antibody responses [95] in contrast to studies in mice [101,112,153].…”

Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery

“…Langerhans cells are dendritic cells that activate T cells and induce a strong immune response and occupy around 20% of the skin's area. On the other hand, M-cells are the microfold cells, which act as sampling ports for any foreign entities encountered in the small intestine upon oral administration [18][19][20][21][22][23]. These M cells house various dendritic cells and immune cells in them.…”

“…Several others have mentioned their usage for oral sustained or controlled release delivery [31,32]. To target the vaccine formulation to M-cells in the Peyer's patches of the intestine upon oral delivery, M-cell targeting agent, Aleuria aurantia lectin (AAL) was used in the formulation [15,20,21]. In addition, immunostimulatory molecules such as IL-2 and IL-12 were added in order to enhance the overall potency of the formulated vaccines.…”