Chimeric antibodies for delivery of antigens to selected cells of the immune system

Abstract

Antibody molecules specific for surface structures of antigen presenting cells that have been modified to include an antigen moiety at a specific site therein to produce novel conjugate antibody molecules are disclosed. These conjugate molecules are produced by genetic modification of genes encoding light and heavy chains of the surface structure specific antibody, and expression in mammalian cells to produce the conjugate antibody. The conjugate antibody retained specificity for antigen presenting cells and contained the antigen moiety. The conjugate antibody molecules deliver the antigen to antigen presenting cells to produce an enhanced immune response to a host immunized therewith. The conjugate antibody molecules and nucleic acid molecules encoding them are useful as antigens and as immunogens in diagnostic and prophylactic applications.

Description

[0001] The present invention is concerned with novel recombinant antibody molecules genetically modified to contain an antigen moiety for the purpose of delivery of the antigen moiety to antigen-presenting cells of the immune system.BACKGROUND OF INVENTION[0002] Current theories of immunology suggest that, in order to provide a potent antibody response, an antigen must be seen by both B cells, which subsequently develop into the antibody producing cells, and also by helper T-cells, which provide growth and differentiation signals to the antigen specific B-cells. Helper T-cells recognize the antigen on the surface of antigen-presenting cells (APC) in association with Class II major histocompatibility complex (MHC) gene products.[0003] There are significant advantages in using proteins and peptides derived from proteins of infectious organisms as part of subunit vaccines. The search for such suitable subunits constitutes a very active area of both present and past research. Advances i...

AI Technical Summary

Problems solved by technology

However, a major stumbling block to the use of such materials as vaccines has been the relatively poor in-vivo immunogenicity of most protein subunits and peptides.

However, the only currently licensed adjuvants for use in humans are aluminum hydroxide and aluminum phosphate, collectively termed alum, which is limited in its effectiveness as a potent adjuvant.

14 to 17), to achieve targeting to APC's; however, most of these latter studies involve in-vitro experiments and lack animal data.

There are some inherent disadvantages with such chemical coupling techniques, such as yields (about 20%) and also the variability factor between different preparations.

There is also no adequate control on the amounts of coupled peptide as well as the exact location of the reaction.

Additionally, further purification is usually required and, therefore, losses in material can be significant.

The common problems encountered in bacterial expression systems include expression as inclusion bodies which require solubilization and refolding with extensive product losses.

The expression of whole antibody is presently not possible in E. coli and, therefore, the monovalent Fab may not have the requisite affinity for in-vivo targeting.

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