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US 2026/0258355 A1Published application
Engineered Expression of Cell Surface and Secreted Sialidase by CAR T Cells for Increased Efficacy in Solid Tumors
AssigneesThe Trustees of the University of Pennsylvania, The United States of America as represented by the Department of Veterans Affairs
InventorsAvery D. Posey, Tiffany King
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Abstract
The present disclosure provides modified immune cells or precursors thereof (e.g. modified T cells) comprising a chimeric cell surface sialidase or a variant sialidase precursor protein. Compositions and methods of treatment are also provided.
Claims29
1-28. (canceled)
A method of treating cancer in a human subject in need thereof, the method comprising:
- administering to the human subject an effective amount of a human immune cell comprising a chimeric cell surface sialidase enzyme, the chimeric cell surface sialidase enzyme comprising:
- (a) an extracellular domain comprising a sialidase selected from the group consisting of Neu1, Neu2, Neu3, and Neu4,
- (b) a heterologous transmembrane domain;
- (c) an intracellular costimulatory signaling domain comprising an intracellular 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;
- and
- (d) an intracellular signaling domain comprising an intracellular signaling domain of a human CD3 zeta chain (CD3z), FcγRIII, FcεRI, 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.
3 more elements
The method 42, wherein the hinge domain comprises a hinge of CD8a.
A method of treating cancer in a human subject in need thereof, the method comprising:
- administering to the human subject an effective amount of a human immune cell comprising a chimeric cell surface sialidase enzyme, the chimeric cell surface sialidase enzyme comprising:
- (i) an amino acid sequence comprising a sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:10, 21, or 38;
- or (ii) an amino acid sequence encoded by a nucleic acid sequence comprising a sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:1, 19, or 40.
Dependencies are inferred from the claim text.