Table 1:
Cell surface receptors expressed on tumor cells and within the tumor microenvironment that have been or have the potential to be* utilized in stem cell-delivered cell surface receptor targeting therapies and their respective targeting agents. Cell surface receptors with differential or unique expression on the surface of tumor cells or cells of the tumor microenvironment are attractive targets for cell surface receptor targeting therapies. *Stem cell (SC) delivered anti-tumor receptor targeting agents have not yet been explored for this receptor type. Abbreviations: TNFR – tumor necrosis factor receptor, DR4/5 – death receptor 4/5, EGFR – epidermal growth factor receptor, IFNAR - Interferon-α/β cell surface receptor complex, GPCR – G protein coupled receptor, BnR – Bombesin receptor, SSTR – somatostatin receptor, ET – endothelin receptors, FR – folate receptor, TfR – transferrin receptor, FGFR – fibroblast growth receptors, TRAIL - Tumor necrosis factor-related apoptosis inducing ligand, oHSV – oncolytic herpes simplex virus, TSP – thrombospondin, scFV- single chain variable fragment, BC – breast cancer, UC – uterine cancer, NB – neuroblastoma, GBM – glioblastoma, NK – natural killer AML – acute myeloid leukemia, ALL – acute lymphoblastic leukemia, LC – lung cancer, OC – ovarian cancer.
| Receptor type | SC delivered anti-tumor targeting agent | Expression in tumor cells and cells of the tumor microenvironment | References |
|---|---|---|---|
| TNFRs | |||
| Death receptors 4 and 5 (DR4/5) | TRAIL | Expressed in non-malignant and malignant cells, suggested to be expressed at higher levels in malignant cells | 120,121 |
| CD137/4–1BB | CD137/4–1BB ligand (CD137L/4–1BBL) | Expressed on T cells | 86 |
| EGFRs | |||
| EGFRvIII | EGFR targeting antibodies or nanobodies (ENb) | Expressed only in glioma, novel variant | 80 |
| EGFR2/HER2 | anti-HER2 antibodies (trastuzaumab) | Overexpressed in BC, gastric, cervical, UC, gallbladder and testicular cancers, bladder carcinomas, and extrahepatic cholangiocarcinomas | 122 |
| Nectin-1 | oHSV | Expressed in neurons, as well as a variety of cancers including NB, GBM, and squamous cell carcinoma. Often predicative of oHSV susceptibility. | 123,124 |
| IFNAR | Type I interferons (IFNα, IFNβ) | Expressed on a variety of tumor cells (fibrosarcoma, cervical, colon, and lung carcinoma, etc.) and immune cells (T cells, NK cells, and dendritic cells) | 64–66,125 |
| CD36 | TSP | Expressed on endothelial cells,present in highly vascularized tumors such as GBM | 62 |
| CD20 | anti-CD20 antibodies (rituximab, scFv–CD20) | Exclusively expressed in B cell precursors, mature B cells, and B cell lymphoma (Hodgkin’s and non-Hodgkin lymphoma) | 84 |
| CD33 | anti-CD33 antibodies (gemtuzumab ozogamicin (Mylotarg), anti- CD33–anti-CD3 bsAb) |
Overexpressed on of the majority of AML cells | 87 |
| CD19 | anti-CD19 antibodies (blinatumomab, anti-CD3–antiCD19 TandAb) | Expressed in B-precursor ALL and B cell lymphoma | 87 |
| CD3 | anti-CD3 antibodies (anti-CD33–anti-CD3 bsAB, TandAb, blinatunmomab, anti-CD3scFv) | Expressed on T cells | 86 |
| GPCRs | |||
| BnR | * | Expressed in GBM, NB, non-small cell and small cell LC (novel receptor), intestinal, thymic, gastrointestinal, lung, and bronchial carcinoid tumors, OC, pancreatic, prostate, BC, head and neck, colon, UC, and renal cancers, Ewing sarcoma, pituitary tumors | 126,127 |
| SSTRs | * | Expressed in small cell LC, prostate, BC, gastric cancers, neuroendocrine tumors, colorectal and hepatocellular carcinoma | 128 |
| ET | * | Expressed in melanoma | 129,130 |
| Integrins | |||
| ανβn (ex ανβ3) | * | Expressed in activated endothelial cells and tumor cells (U87MG GBM cells) | 131,132 |
| α−3 | * | Expressed in OC and BC, and melanoma | 133 |
| FR (α, β, γ) | * | Expressed in OCand BC, endometrial and renal cell carcinomas, lung andenocarcinomas and mesotheliomas | 134 |
| TfRs | |||
| TfR1 (CD71) | * | Overexpressed in glioma and GBM, expressed in BC and OC | 135–137 |
| FGFRs | * | Alterations in expression in BC, bladder, prostate, LC, and haematological malignancies | 138 |