Engineered expression of cell surface and secreted sialidase by CAR T cells for increased efficacy in solid tumors

A modified immune cell or precursor cell thereof, comprising a chimeric cell surface sialidase (neuraminidase) enzyme comprising:

• (a) an extracellular portion comprising a sialidase (neuraminidase), wherein the sialidase is selected from the group consisting of Neu1, Neu2, Neu3, and Neu4,
• (b) a heterologous transmembrane domain capable of tethering the extracellular portion to a cell surface;
• and
• (c) an intracellular region comprising a costimulatory signaling domain and an intracellular signaling domain;
• wherein the intracellular signaling domain comprises a cytoplasmic signaling domain of a human CD3 zeta chain (CD3z), FcγRIII, FcsRI, a cytoplasmic tail of an Fc receptor, an immunoreceptor tyrosine-based activation motif (ITAM) bearing cytoplasmic receptor, TCR zeta, FcR gamma, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, or CD66d;
• and
• wherein the costimulatory signaling domain comprises a costimulatory domain of a protein in the TNFR superfamily, CD28, 4-1BB, OX40, PD-1, CD7, LIGHT, CD83L, DAP10, DAP12, CD27, CD2, CD5, ICAM-1, LFA-1, Lck, TNFR-I, TNFI-II, Fas, CD30, CD40, ICOS, NKG2C, or B7-H3.