Table 1.
Potential clinical trial opportunities—single agents based on IOTN investigators' research
| Agent | Category | Indication | Potential combination therapies | Reference |
|---|---|---|---|---|
| DR-18 (decoy resistant IL-18 binding protein) | Immune checkpoint | All solid tumors | —a | (36) |
| Bempegaldesleukin, a CD122-preferential IL-2 pathway agonist | Immune checkpoint | All solid tumors | Immune checkpoint blockade + radiation therapy | (25) |
| CD-19 reactive CAR-T cells with NR4A-triple knockout | Adoptive cell therapy | Solid tumors | NR4A inhibition + immune checkpoint inhibition | (9) |
| Anti-HER2 CAR-T (CD8-positive) cells | Adoptive T-cell therapy with chimeric receptors | HER2-expressing tumors | —a | (11) |
| Orthogonal IL-2 receptor extracellular domain fused with IL-9 receptor for intracellular domain for CAR-T cells | Adoptive cell therapy | Solid tumors | —a | (13) |
| Anti-BTN3A1 antibodies (clone CTX-2026) | Solid tumors | Adoptive cellular therapy and immune checkpoint | (27) | |
| PD-L1 × CD3 bispecific antibody | Immune checkpoint | Solid tumors | Potentially combined with cellular therapy and BTN3A1 antibody, as well | (37) |
| SynNotch-CAR-T cells | Adoptive cell therapy | Glioblastoma | Novel delivery method, can be combined with immune checkpoint inhibitor and cellular therapy | (12) |
| B7-H3 CAR-T cells | Novel delivery method | Glioblastoma | —a | (28) |
| C/EBP homologous protein inhibition of CD8-positive T cells | Adoptive cell therapy | Ovarian, breast, and other solid tumors | —a | (38) |
| Two novel variant TGF-β receptors that couple the TGF-β–dominant negative receptor to intracellular signaling domains, mediating NK cell activation, 1) NKA: DNAX-activation protein 12 and 2) NKCT: synthetic Notch-like receptor | Adoptive cell therapy | Neuroblastoma | Combined with standard checkpoint inhibitors or novel checkpoint pathways described previously | (39) |
| CDN-Mn2+ particle (metalloimmunotherapy) | Vaccine | Solid tumors | —a | (40) |
| Nanoparticle STING agonist: a pH-sensitive polymer bearing a 7-member ring with a tertiary amine | Vaccine and immune activation | Solid tumors | Combined with checkpoint inhibitor therapy (anti–PD-1) | (41) |
| Combined theranostic alkylphosphocholine analog 90Y-NM600 with moderate-dose (12-Gy) external beam radiation therapy | Radioimmunotherapy | Virtually any tumor any location | —a | (26) |
| Four shared frameshift peptide neoantigens (Nacad [FSP-1], Maz [FSP-1], Senp6 [FSP-1], Xirp1 [FSP-1]) | Immunoprevention vaccine approach | Patients with Lynch syndrome to prevent gastrointestinal malignancies | —a | (42) |
| Genetic transfer of T-cell receptor from neoantigen-specific T-cell clones into peripheral blood T cells was conducted to generate neoepitope-specific T cells | Vaccine | Ovarian and other solid tumors | —a | (43) |
| Neoantigen vaccine for identified tumor specific gene-gene fusion transcripts | Vaccine | Osteosarcomas and other solid tumors | —a | (44) |
| Multifunctional bacterial membrane-coated nanoparticle composed of an immune-activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups + radiation | Radioimmunotherapy | Solid tumors | —a | (45) |
| CD8 T cells engineered with the CXCR6-CXCL16 axis | Vaccine and adoptive cellular therapy | Ovarian and other solid tumors | —a | (15) |
| Macroporous alginate gels loaded with granulocyte-macrophage colony-stimulating factor for concentrating dendritic cells, CpG oligonucleotides, and a doxorubicin-iRGD conjugate | Vaccine and chemoimmunotherapy | Breast and other solid tumors | —a | (46) |
| Glycan-dependent T-cell recruiters targeting tumor-associated carbohydrate antigens | Bispecific proteins and CAR-T cells | Solid and liquid tumors | Checkpoint inhibitors, multiple glycan-dependent T-cell recruiters | Unpublished (lab of Dr Demetriou) |
a
No value given because a single immunotherapy. CAR = chimeric antigen receptor; IL = interleukin; NK = natural killer; PD-1 = programmed cell death 1 protein; PD-L1 = programmed cell death 1 ligand 1; TGF-β = tyrosine kinases transforming growth factor β.