Dialdehydes as immunostimulatory adjuvants and cross-linkers for producing immunogenic preparations and generating pressure and cross-linked treated cells for enhancing and augmenting the immune response against cancers, tumors and pathogenic diseases

摘要

The invention describes a method of preincubating cells with dialdehydes, preferably a 2',3'-nucleoside or nucleotide dialdehyde as cross-linkers, prior to modifying the cell membrane components of the preincubated cells by exposure to hydrostatic pressure to produce potent immunogenic preparations. The pressure and crosslinker treatment of cells is termed PCL-modification. Preincubation PCL-modification allows the dialdehyde to serve as both a cross-linker of membrane components and a source of monoaldehyde groups on the cell surface, thus providing adjuvanting and costimulatory function to the cells. Also provided are immunogenic compositions comprising dialdehyde and antigen for augmenting and enhancing the immune response to a specific antigen. A reversible covalent chemical bond is formed between the dialdehyde component and the antigen component via one monoaldehyde of the dialdehyde. The other monoaldehyde can react with a biological response molecule or adjuvant for slow or prolonged release and enhancement of the immune response after immunization. Further provided are potent immunogens and immune response stimulators produced by PCL-treatment of antigen-presenting cells (APC) that have been pulsed or co-cultured with cancer, tumor or infected cell-associated antigens. The PCL-modified, antigen-pulsed APC can be used in immunogenic preparations and vaccines to increase immunogenicity and elicit vigorous cell-mediated responses and TH1 cytokine production. These cells can also be used with proliferated, antigen-specific T cells in immunogenic preparations and vaccines and in immunoadoptive therapies to treat and prevent cancers, tumors and infection. Biological response molecules, e.g., immunostimulatory cytokines, lymphokines and growth factors, can be coupled to the PCL-treated, antigen-pulsed compositions and APC to further enhance and augment the immune response.