Vaxiion has developed several methods of converting recombinant bacterial minicells (rBMCs) into targeted drug delivery products. In general, these can be separated into two basic targeting strategies; non-antibody-based targeting & antibody-based targeting approaches. These two functionalization methodologies combine to allow for rapid, simple and versatile design of BMC-based targeted delivery products.
Targeted Drug Delivery with Recombinant Bacterial Minicells (rBMCs)
Antibody Targeted rBMCs
Antibody-based targeting of rBMCs to tumor or other cells is mediated by the surface display of antibodies or common antibody derivatives, such as single chain antibodies. Vaxiion has developed several methodologies for functionalizing the surface of rBMCs with targeting antibodies. In one approach, antibodies and antibody derivatives are physically attached to the surface of rBMCsto make them targeting competent. Physical attachment methods include chemical cross-linking, the use of bi-specific antibodies and antibody derivatives, and the attachment of Fc-containing antibodies and antibody derivatives to rBMCs containing the Fc-binding portion of Protein A or Protein G on their surfaces. As an alternative to the physical attachment of antibodies to rBMCs, Vaxiion has also engineered a host of different recombinant membrane anchored fusion proteins capable of displaying functional single chain antibody fragments on the rBMC surface.
Non-Antibody Targeted rBMCs
Given its extreme simplicity, one of Vaxiion's preferred approaches to conferring targeting properties to our rBMC products is to engineer through recombinant expression the display of non-antibody targeting proteins on the rBMC surface. One example of this includes the expression and display of heterologous bacterial adhesin and invasin protein family members. Adhesins and invasins are bacterial cell-surface proteins capable of targeting specific mammalian surface proteins with antibody-like specificity and affinity. In some instances, the mammalian cell-surface targets of bacterial adhesins and invasins are tumor-specific, as is the case with our lead product, VAX014, whose surface is decorated with the dual-specific alpha3beta1 (α3β1) and alpha5beta1 (α5β1) integrin-targeting protein, Invasin, from Yersinia pseudotuberculosis.