Nucleic acid-containing lipid nano-particle and use thereof
The present invention provides a lipid nanoparticle containing the following (a) to (c): (a) a nucleic acid encoding a chimeric antigen receptor (CAR) or an exogenous T cell receptor (TCR); (b) a cationic lipid; and (c) a non-cationic lipid. The present invention also provides a CAR- or exogenous TCR-expressing immunocyte obtained by introducing the lipid nanoparticle into in vivo or ex vivo T cells, and an in vivo or ex vivo therapeutic approach using the immunocytes for disease such as cancer and the like.
1 . A medicament comprising a lipid nanoparticle, wherein the lipid nanoparticle comprises:
(a) a nucleic acid encoding a chimeric antigen receptor or an exogenous T cell receptor;
(b) a cationic lipid or a salt thereof, the cationic lipid being selected from the group consisting of compound 12 and compound 35:
and
(c) a non-cationic lipid, wherein a surface of the lipid nanoparticle has one or more ligands that target T cells and that provide increased expression of a chimeric antigen receptor or an exogenous T cell receptor encoded by a nucleic acid delivered by the lipid nanoparticle to the target T cells compared to the same lipid nanoparticle lacking the one or more ligands.
2 . The medicament according to claim 1 , wherein the medicament is a prophylactic or therapeutic drug for cancer.
3 . The medicament according to claim 1 , wherein the medicament introduces a chimeric antigen receptor or an exogenous T cell receptor gene into an in vivo T cell to induce an expression thereof.
4 . The medicament according to claim 1 , wherein the aforementioned nucleic acid is mRNA or DNA.
5 . The medicament according to claim 1 , wherein the aforementioned non-cationic lipid is phospholipid, cholesterol and/or PEG lipid.
6 . The medicament according to claim 1 , wherein the aforementioned ligands are comprising an antigen binding domain of one or more antibodies selected from the group consisting of an antibody against CD3, an antibody against CD4, an antibody against CD8 and an antibody against CD28.
7 . The medicament according to claim 1 , wherein the aforementioned ligands are comprising an antigen binding domain of an antibody against CD3 and/or an antibody against CD28.
8 . The medicament according to claim 1 , wherein the aforementioned cationic lipid is a compound 12:
or a salt thereof.
9 . The medicament according to claim 1 , wherein the aforementioned cationic lipid is a compound 35:
or a salt therof.
10 . The medicament according to claim 8 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD3.
11 . The medicament according to claim 9 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD3.
12 . The medicament according to claim 8 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD4.
13 . The medicament according to claim 9 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD4.
14 . The medicament according to claim 8 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD8.
15 . The medicament according to claim 9 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD8.
16 . The medicament according to claim 8 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD28.
17 . The medicament according to claim 9 , wherein the aforementioned ligand is comprising an antigen binding domain of an antibody against CD28.