Building and Characterizing Antibody-Targeted Lipidic Nanotherapeutics

Merrimack Pharmaceuticals, Cambridge, Massachusetts, USA.
Methods in enzymology (Impact Factor: 2.09). 01/2012; 502:139-66. DOI: 10.1016/B978-0-12-416039-2.00007-0
Source: PubMed


Immunoliposomes provide a complementary, and in many instances advantageous, drug delivery strategy to antibody-drug conjugates. Their high carrying capacity of 20,000-150,000 drug molecules/liposome, allows for the use of a significantly broader range of moderate-to-high potency small molecule drugs when compared to the comparably few subnanomolar potency maytansinoid- and auristatin-based immunoconjugates. The multivalent display of 5-100 antibody fragments/liposome results in an avidity effect that can make use of even moderate affinity antibodies, as well as a cross-linking of cell surface receptors to induce the internalization required for intracellular drug release and subsequent activity. The underlying liposomal drug must be effectively engineered for long circulating pharmacokinetics and stable in vivo drug retention in order to allow for the drug to be efficiently delivered to the target tissue and take advantage of the site-specific bioavailability provided for by the targeting arm. In this chapter, we describe the rationale for engineering stable immunoliposome-based therapeutics, methods required for preparation of immunoliposomes, as well as for their physicochemical and in vivo characterization.

Download full-text


Available from: Zhaohua Huang, Sep 09, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics international conferences, and the 2011 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 5-8, 2011 in San Diego, CA. The meeting drew ~800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a preview to the main events, a pre-conference workshop held on December 4, 2011 focused on antibodies as probes of structure. The Antibody Engineering Conference comprised eight sessions: (1) structure and dynamics of antibodies and their membrane receptor targets; (2) model-guided generation of binding sites; (3) novel selection strategies; (4) antibodies in a complex environment: targeting intracellular and misfolded proteins; (5) rational vaccine design; (6) viral retargeting with engineered binding molecules; (7) the biology behind potential blockbuster antibodies and (8) antibodies as signaling modifiers: where did we go right, and can we learn from success? The Antibody Therapeutics session comprised five sessions: (1)Twenty-five years of therapeutic antibodies: lessons learned and future challenges; (2) preclinical and early stage development of antibody therapeutics; (3) next generation anti-angiogenics; (4) updates of clinical stage antibody therapeutics and (5) antibody drug conjugates and bispecific antibodies.
    Full-text · Article · Mar 2012 · mAbs
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multivalent interactions of biological molecules play an important role in many biochemical events. A multivalent ligand comprises of multiple copies of ligands conjugated to scaffolds, allowing the simultaneous binding of multivalent ligands to multiple binding sites or receptors. Many research groups have successfully designed and synthesized multivalent ligands to increase the binding affinity, avidity and specificity of the ligand to the receptor. A multimeric ligand is a promising option for the specific treatment of diseases. In this review, the factors affecting multivalent interactions, including the size and shape of the ligand, geometry and an arrangement of ligands on the scaffold, linker length, thermodynamic, and kinetics of the interactions are discussed. Examples of the multivalent ligand applications for therapeutic delivery are also summarized.
    No preview · Article · Oct 2012 · Therapeutic delivery
  • Chapter: References

    No preview · Chapter · Jan 2013
Show more