DELIVERY OF MONOCLONAL ANTIBODIES FROM MICROENCAPSULATED CELLS
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Date
2020
Authors
Ashimova, A.
Hortelano, G.
Journal Title
Journal ISSN
Volume Title
Publisher
International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana
Abstract
Monospecific immunoglobulins (monoclonal antibodies, MAb) of therapeutic interest have received
significant attention since their development by Milstein and Kohler in 1975. The exquisite specificity of
MAb, or the ability to bind exclusively to its target makes it a very promising tool in medical diagnosis
and therapy. A large number of MAbs have been licensed and are used in the clinic today, particularly as
anticancer agents. Nonetheless, the very high cost associated to the production and purification of MAbs
is a significant challenge to their successful commercialization, since a treatment can cost upwards of
$100,000 per patient. Since MAb purification is the greatest technical and economic challenge this proposal
aims at exploring a novel strategy for the sustained and constant delivery of MAbs. The microcapsules
are produced with electrostatic bead generation of the hydrogel alginate, which after gelation are
cross-linked with cationic poly-L-lysine to produce stable microcapsules that are 200-400 micrometers in
diameter. In addition to the polymer, the choice of judicious cells suitable for encapsulation is critical for
the success of the proposed strategy. The microcapsules are permeable to IgG and nutrients, but not to
immune cells. As a result of the immune isolation the enclosed allogeneic cells are not rejected, making
tissue matching unnecessary for the treatment. This proposal is aimed at investigating the potential of
encapsulated myoblasts and MSC cells to produce –and secrete- clinically relevant levels of monoclonal
antibodies (MAbs) aimed at preventing tumor growth such as epidermal growth factor receptor (EGFR)
as well as MAb against CD-20, to deplete tumorigenic B lymphocytes. Both MAbs have been proved efficacious
in patients with carcinoma and lymphoma cancers, respectively. If successful, encapsulated cells
will deliver constant, sustained clinically relevant amounts of functional MAb, making antibody delivery
cost-effective. This novel strategy could have wide applications in the treatment of medical conditions
such as various types of cancer and autoimmune diseases, which are already treated with monoclonal
antibodies.
Description
Keywords
cell encapsulation, microcapsule, monoclonal antibodies, alginate, therapeutic delivery, Research Subject Categories::MEDICINE