Use of a stromal antigen to deliver cell-based cancer therapy to a solid tumor
AssigneeThe Regents of the University of California
InventorsWendell A. LIM, Gregory ALLEN
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Abstract
Provided herein is a cytotoxic immune cell that is primed by and/or whose cytotoxicity within the tumor microenvironment is enhanced by binding to a stromal marker, e.g., Fibroblast Activation Protein Alpha (FAP). In some embodiments, the cells may contain a protein circuit that contains at least two components, wherein one of the components binding-triggered transcriptional switch that is activated by binding to the stromal marker. The second component may be a nucleic acid encoding an immune receptor (e.g., a chimeric antigen receptor or TCR) that is activated by binding to a cancer-specific antigen and/or a pro-inflammatory cytokine.
Claims18
An engineered immune cell comprising a molecular circuit comprising the following components:
- (a) an anti-stromal marker binding-triggered transcriptional switch (BTTS) and one or both of:
- (b) a nucleic acid encoding a pro-inflammatory protein, and
- (c) a nucleic acid encoding an immune receptor that is activated by binding to an antigen listed in Table 1 on a cancer cell;
- wherein the stromal marker is:
- (i) FAP (Fibroblast Activation Protein Alpha), (ii) PDPN (Podoplanin), (iii) CDH11 (Cadherin 11), (iv) PDGFR (Platelet-derived growth factor) or (v) LRRC15 (Leucine Rich Repeat Containing protein 15), and
- wherein binding of the BTTS to the stromal on the surface of a stromal cell activates expression of the pro-inflammatory protein of (b) and/or the immune receptor of (c).
An engineered immune cell comprising the following components:
- (a) an anti-stromal marker BTTS;
- (b) a nucleic acid encoding a pro-inflammatory protein,
- wherein the stromal marker is:
- (i) FAP (Fibroblast Activation Protein Alpha), (ii) PDPN (Podoplanin), (iii) CDH11 (Cadherin 11), (iv) PDGFR (Platelet-derived growth factor) or (v) LRRC15 (Leucine Rich Repeat Containing protein 15), and
- wherein binding of the BTTS to the stromal marker on the surface of a stromal cell activates expression of the pro-inflammatory protein of (b);
- and
- (c) an immune receptor that is activated by binding to an antigen listed in Table 1 on a cancer cell, wherein expression of the immune receptor is constitutive in the cell.
Dependencies are inferred from the claim text.