Lipid nanoparticles and methods of manufacture and use thereof

A lipid nanoparticle (LNP) comprising:

• (a) an ionizable cationic lipid:
• or a salt thereof;
• (b) cholesterol;
• (c) 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC);
• (d) PEG 2000-dipalmitoyl-glycerol (DPG-PEG2K);
• and
• (e) a lipid-immune cell targeting group conjugate comprising the compound of formula distearoyl-phosphatidylethanolamine (DSPE)-polyethylene glycol (PEG)-antibody conjugate, wherein the DSPE is covalently coupled to the antibody via a linker comprising PEG,
• wherein the antibody is an immunoglobulin single variable domain (ISVD) that specifically binds to human CD8alpha, comprising complementarity-determining regions 1 (CDR1), 2 (CDR2), and 3 (CDR3) of an ISVD having the sequence of SEQ ID NO:
• 169,
• wherein the LNP encapsulates an mRNA, and the mRNA encodes a polypeptide comprising a chimeric antigen receptor (CAR),
• wherein the CAR comprises an antibody that specifically binds to human CD22,
• wherein the antibody that specifically binds to human CD22 is an anti-CD22 ScFv, and
• wherein the anti-CD22 ScFv comprises a CDR1, a CDR2, and a CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:
• 523, and a CDR1, CDR2, and a CDR3 of a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:
• 524.