Table 1.
Examples of next-generation antibody modalities for GPCRs and ion channels
| Target class | Modality | Organization | Indication | Stage |
|---|---|---|---|---|
| GPCRs | ||||
| FZD10 | ADC (90Y) | Oncotherapy Science | Synovial sarcoma | Phase 1 |
| LGR5 × EGFR | BS (with ADCC) | Merus | Metastatic CRC | Phase 1 |
| SSTR2 × CD3 | BS | Xencor | NET/GIST | Phase 1 |
| GPRC5D × CD3 | BS (duobody) | Genmab/Janssen | Myeloma | Phase 1 |
| CCR7 | ADC | Novartis | CLL | Phase 1 |
| GPR20 | ADC | Daiichi Sankyo | GIST | Phase 1 |
| CXCR4 | Alternative scaffold—iBody | AdAlta | Fibrosis | Phase 1 |
| CCR4 | Diabody immunotoxin | MGH/Harvard University | Cancer | Preclinical |
| CXCR4 | ADC | John Hopkins | AML | Preclinical |
| LGR5 | ADC (89Zr) | Texas Therapeutics Institute | CRC (and immunoPET) | Preclinical |
| PAC1 × CGRP-R | BS | Amgen | Migraine | Preclinical |
| CXCR5 × CD3 | BS | Max-Delbrück-Center of Molecular Medicine | Cancer | Preclinical |
| Calcitonin R | ADC | Monash | GBM | Preclinical |
| GLP-1R × GCG | BS | Calibr | Metabolic diseases | Preclinical |
| SSTR4 | Peptide–Ab conjugate | Peptide Logic | Pain | Preclinical |
| EMR1 | CAR-T | Humanigen | Eosinophilic leukemia | Preclinical |
| GnRH | CAR-T | Protheragen | Ovarian, prostate, pancreatic cancer | Preclinical |
| GPRC5D | CAR-T | MSK/Juno Therapeutics | Myeloma | Preclinical |
| CB1 × AT1 | BS | Ichan School of Medicine | Liver fibrosis | Discovery |
| CCR5 | Biparatopic | Scripps Research Institute | HIV | Discovery |
| CCR5 × HIV envelope | BS/TS | Scripps Research Institute | HIV | Discovery |
| GABAB × TfR | BS | Denali | Alzheimer’s disease | Discovery |
| Ion channels | ||||
| P2X7 | Nanobody | Univ Med Centre Hamburg | Autoimmune | Preclinical |
| nfP2X7 | CAR-T | Biosceptre | Hematological malignancies | Discovery |
| Solid tumors | Discovery | |||
| Kv10.1 | Nanobody–TRAIL fusion | Max Planck Institute | Cancer | Discovery |
| Kv2.1 | Nanobody | Institut Pasteur Tunis | Cancer | Discovery |
| TRPV4 | i-Body | AdAlta | Fibrosis | Discovery |
| Kv1.3 | Knot-Body | Maxion Therapeutics | Autoimmune | Discovery |
| Nav1.7 | Ab–GPTx1 peptide conjugate | Amgen | Pain | Discovery |
| Ab–JzTx-V peptide conjugate | Amgen | Pain | Discovery | |
These encompass a wide variety of bispecific formats, ADCs, CAR-T and antibodies with an engineered activity, such as peptide–antibody conjugates. BS, bispecific; TS, trispecific; Ab, antibody; CRC, colorectal cancer; NET, neuroendocrine tumor; GIST, gastrointestinal stromal tumor; CLL, chronic lymphocytic leukemia; AML, adult acute myeloid leukemia; ImmunoPET, Immuno-positron emission tomography; GBM, glioblastoma.