Soluble antibody complexes for T cell or NK cell activation and expansion
This disclosure provides compositions and methods for the activation and expansion of human T cells or NK cells using soluble monospecific antibody complexes.
1. A method of activating human NK cells comprising culturing a sample containing human NK cells with a composition comprising at least one soluble monospecific complex, wherein each soluble monospecific complex comprises two antibodies or F(ab′) 2 fragments thereof which are linked and bind to the same antigen on the human NK cells,
wherein the at least one soluble monospecific complex comprises two anti-CD335 antibodies or F(ab′) 2 fragments thereof that bind a CD335 antigen on the human NK cells.
2. A method of activating human NK cells comprising culturing a sample containing human NK cells with a composition comprising at least two soluble monospecific complexes, wherein each soluble monospecific complex comprises two antibodies or F(ab′) 2 fragments thereof which are linked and bind to the same antigen on the human NK cells,
wherein a first soluble monospecific complex of the composition comprises two anti-CD335 antibodies or F(ab′) 2 fragments thereof that bind a CD335 antigen on the human NK, cells, and
wherein the composition further comprises a second soluble monospecific complex comprising two anti-CD2 antibodies or F(ab′) 2 fragments thereof that bind a CD2 antigen on the human NK cells.
3. The method according to claim 1 wherein each soluble monospecific complex is a tetrameric antibody complex.
4. The method according to claim 3 wherein the tetrameric antibody complex (TAC) is composed of two antibodies from a first animal species bound by two antibody molecules from a second animal species that bind to the Fc portion of the antibodies of the first animal species.
5. The method according to claim 1 , where the NK cell activation is enhanced NK cell proliferation compared to NK cells cultured in the absence of the soluble monospecific complex.
6. The method according to claim 1 , where the NK cell activation is enhanced cytokine production compared to NK cells cultured in the absence of the soluble monospecific complex.
7. The method according to claim 1 , where the NK cell activation is enhanced NK cell expansion compared to NK cells cultured in the absence of the soluble monospecific complex.
8. The method according to claim 2 wherein each soluble monospecific complex is a tetrameric antibody complex.
9. The method according to claim 8 wherein the tetrameric antibody complex (TAC) is composed of two antibodies from a first animal species bound by two antibody molecules from a second animal species that bind to the Fc portion of the antibodies of the first animal species.
10. The method according to claim 2 , where the NK cell activation is enhanced NK cell proliferation compared to NK cells cultured in the absence of the soluble monospecific complex.
11. The method according to claim 2 , where the NK cell activation is enhanced cytokine production compared to NK cells cultured in the absence of the soluble monospecific complex.
12. The method according to claim 2 , where the NK cell activation is enhanced NK cell expansion compared to NK cells cultured in the absence of the soluble monospecific complex.