Table 2.
Pipeline development: TCR-based therapy programs and their targets
| Company/institution | TCR program(s) (investigational) | Target | Indication(s) | Key features |
|---|---|---|---|---|
| Adaptimmune | ADP-A2M4 SPEAR T-cells | MAGE-A4 | Synovial Sarcoma | TCR (ADP-A2M4) targeting metastatic or inoperable (advanced) Synovial Sarcoma or MRCLS who have received prior chemotherapy and whose tumor expresses the MAGE-A4 tumor antigen. Evaluating urothelial (bladder) cancers, melanoma, head and neck cancer, ovarian cancer, NSCLC, esophageal cancer, gastric cancers, synovial sarcoma, and Myxoid Round Cell Liposarcoma (MRCLS). Adapted to mixed solid tumors secondary studies |
| Adaptimmune | ADP-A2M4CD8 SPEAR T-cell | MAGE-A4 | Solid Tumors | TCR (ADP-A2M4CD8) which also expresses the CD8α co-receptor alongside the engineered TCR that targets MAGE-A4. Preclinical data indicate that co-expression of CD8α may broaden the immune response against solid tumors and increase antitumor activity by leveraging CD4 + cells into CD8 + killer or cytotoxic T-cells while retaining their CD4 + helper function |
| Adaptimmune | ADP-A2M10 T-cell | MAGE-A10 | NSCLC, Melanoma, Bladder, Head and Neck | TCR (ADP-A2M10) targeting MAGE-A10 with potential ability to bind target peptides from multiple cancer types |
| Adaptimmune | ADP-A2AFP SPEAR T-cell | AFP | Hepatocellular Carcinoma | TCR (ADP-A2AFP) in SPEAR T-cell product which targets alpha-fetoprotein (AFP). Currently in Phase I clinical trial for the treatment of patients with hepatocellular carcinoma (liver cancer) |
| Bluebird Bio | MCC1 TCR | MCPyV | Merkel cell carcinoma | Autologous CD4 + and CD62L-expressing CD8 + T-cells expressing the high affinity T-cell receptor (TCR) A2-MCC1, specific for the human leucocyte antigen (HLA)-A02-restricted Merkel cell polyomavirus (MCPyV; MCV) viral oncoprotein. Final product is a cytotoxic T-lymphocyte (CTL) that targets tumor cells expressing the MCPyV viral oncoprotein. MCPyV viral oncoprotein is highly expressed in Merkel cell carcinoma (MCC) caused by MCPyV |
| Bluebird Bio/Medigene | MAGE-A4 TCR | MAGE-A4 | Solid Tumors/Melanoma | Autologous human T lymphocytes transduced with MAGE-A4 as a co-receptor-independent TCR. After isolation, transduction, expansion, and reintroduction, MAGE-A4-specific TCR gene-transduced T lymphocytes bind to tumor cells expressing MAGE-A4. Effecting mechanism both inhibiting growth and increased cell death for MAGE-A4-expressing tumor cells. MAGE-A4 is overexpressed by a variety of cancer cell types |
| Kite/Gilead Sciences | KITE-718 | MAGE-A3 and/or MAGE-A6 | Solid Tumors/Advanced Cancers | Genetically modified T-cells which target tumor cells that express MAGE-A3 and/or MAGE-A6 in patients with solid tumors with relapsed or refractory disease after a systemic standard of care treatment |
| Kite/Gilead Sciences | KITE-439 | HPV16 E6 and HPV16 E7 | Solid Tumors/Advanced Cancers | Genetically modified T-cells which target cells that express HPV16 + solid tumors in patients with relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and not amenable to locoregional definitive therapy |
| Kite/Gilead Sciences | KITE-439 | HPV16hat HOV | Solid Tumors/Advanced Cancers | Genetically modified T-cells which target cells that express HPV16 + solid tumors in patients with relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and not amenable to locoregional definitive therapy |
| Immatics | IMA201-101 | MAGE-A4/8 | Solid Tumors | ACTengine IMA201 genetically engineered T-cells (TCR-T) targeting MAGE-A4 or MAGE-A8 in patients with various solid tumors, including HNSCC, squamous NSCLC, subtypes of sarcoma and other solid tumor indications |
| Immatics | IMA202-101 | MAGE-A1 | Solid Tumors | ACTengine IMA202 genetically engineered T-cells (TCR-T) targeting MAGEA1 in patients with diverse solid tumors, including squamous NSCLC, hepatocellular carcinoma (HCC) and others |
| Immatics | IMA203-101 | PRAME | Solid Tumors | ACTengine IMA203 genetically engineered T-cells (TCR-T) targeting PRAME in patients with a broad range of solid tumor types, including uterine cancer, ovarian cancer, melanoma, subtypes of sarcoma, squamous NSCLC and others |
| Juno | JTCR016 | WT1 |
Stage III/IV NSCLC Mesothelioma |
Autologous CD8 + T-cells genetically-modified to express a high affinity WT1-specific T-cell receptor targeting tumors in patients with stage III-IV non-small cell lung cancer (NSCLC) or mesothelioma |
| TCR2 Therapeutics | TC-210 | Mesothelin | Ovarian Cancer, NSCLC, MPM, Cholangiocarcinoma | TCR-based adoptive therapy which targets mesothelin-positive solid tumors. Mesothelin is highly expressed in solid tumors and has a correlation with poor prognosis and tumorigenesis |
| Tmunity |
NY-ESO-1 TCR-T Triple Knockout TCR (NYCE) |
NY-ESO-1 | Melanoma/Synovial Sarcoma | TCR-based adoptive therapy (NYCE) targeting NY-ESO-1 with designated target-binding capacity in melanoma and synovial sarcoma tumor types |
| Tmunity | H3.3K27M TCR | H3.3K27M | Diffuse intrinsic pontine glioma | Human T-cells transduced with a TCR that specifically targets the H3.3.K27M epitope and kills HLA-A2 + H3.3.K27M + glioma cells both in vitro and in vivo |
| Ziopharm | Sleeping Beauty TCR-T Targeting Neoantigens |
NY-ESO-1 Personalized TCR-T (3 programs) |
Multiple Solid Tumors | Genetically modified TCR therapies that target neoantigens. Sleeping Beauty’s non-viral (transposon/transposase) gene transfer system is suited for developing genetically modified TCR therapies that target neoantigens because of its very rapid manufacturing capability |