Recombinant antibody cytokine fusion proteins
OwnerStephen D. Gilliesinventor
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Abstract
Immunoconjugates for the selective delivery of a cytokine to a target cell are disclosed. The fusion proteins are comprised of an immunoglobulin heavy chain having a specificity for the target cell, such as a cancer or virus-infected cell, and a cytokine, such as lymphotoxin, tumor necrosis factor alpha, interleukin-2, or granulocyte-macrophage colony stimulating factor, joined via its amino terminal amino acid to the carboxy-terminus of the immunoglobulin. Nucleic acid sequences encoding these fusion proteins and methods of their preparation by genetic engineering techniques are also disclosed.
Claims21
A recombinant immunoglobulin (Ig) chain comprising:
- an Ig heavy chain and a cytokine which elicits a cytokine-specific biological response by a cell bearing a receptor for said cytokine, said Ig heavy chain comprising an N-terminal variable region specific for a cell bearing a cell surface antigen;
- and, CH1 and CH2 domains, said Ig heavy chain being joined at its carboxy-terminus by a peptide bond to the amino terminal amino acid of the cytokine.
A cytokine immunoconjugate comprising:
- (a) a recombinant immunoglobulin (Ig) heavy chain having an N-terminal variable region specific for a cell bearing a cell surface antigen of a cancer cell or a virus-infected cell, a constant region comprising CH1 and CH2 domains, and a cytokine joined to the carboxy-terminus of said constant region by a peptide bond, wherein said cytokine elicits a cytokine-specific biological response by a cell bearing a receptor for said cytokine;
- and
- (b) an Ig light chain having a variable region specific for said cell surface antigen, said Ig heavy and light chains forming together a functional antigen-binding site, such that said immunoconjugate displays both antigen-binding specificity and cytokine biological activity.
Dependencies are inferred from the claim text.