Table 1.
Drug conjugates approved by the FDA
| Drug name | Drug type | Mechanism | Indication | Year of FDA approval |
|---|---|---|---|---|
| SGN-35 | ADC | SGN-35 binds specifically to CD30-positive tumor cells and releases the cytotoxic drug MMAE within the target cells [396–399] | Hodgkin lymphoma, large cell lymphoma | 2011 |
| T-DM1 | ADC | T-DM1 retains the effect of trastuzumab and inhibits HER2 receptor signaling while inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and inhibiting HER2 extracellular domain shedding in HER2-overexpressing human breast cancer cells [400, 401] | Breast cancer | 2013 |
| Inotuzumab ozogamicin | ADC | When the antibody binds to the CD22 receptor on the surface of B cells, the drug exerts a strong cytotoxic effect on CD22+ B-cell lymphoma [402–405] | Acute lymphoblastic leukemia | 2017 |
| Moxetumomab pasudotox | ADC | Internalization of moxetumumab pasudotox-tdfk leads to ribosylation of extension factor 2 ADP, inhibition of protein synthesis and apoptotic cell death [406–409] | Relapsed or refractory hairy cell leukemia | 2018 |
| Polatuzumab vedotin | ADC | Chemotherapy drugs bind specifically to the protein CD79b on the surface of B cells and release it into the B cells, thereby inhibiting cell division and inducing cell apoptosis [137, 410–412] | Diffuse large B-cell lymphoma | 2019 |
|
Enfortumab vedotin |
ADC | The anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to cells expressing Nectin-4, subsequent internalization of the ADC-Nectin-4 complex, and release of MMAE through proteolytic cleavage [270, 413–418] | Urothelial cancer | 2019 |
| T-DXd | ADC | T-DXd connects antibodies and chemotherapeutic drugs through special connectors. The antibody part can accurately locate cancer cells, deliver the chemotherapeutic drugs to the cancer cells, and accurately kill cancer cells. At the same time, it can kill adjacent tumor cells through transmembrane action [419–422] | Breast cancer | 2019 |
| Sacituzumab govitecan | ADC | Sacituzumab govitecan can deliver chemotherapeutic drugs directly to the tumor cell microenvironment by combining antibodies with TROP-2 antigen expressed on most breast cancer cells [423–427] | Triple-negative breast cancer | 2020 |
| Belantamab mafodotin | ADC | Belantamab mafodotin blmf exerts antitumor activity on multiple myeloma cells. It can kill tumor cells through MMAF-induced apoptosis, antibody-dependent cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADCP) [73, 428–432] | Relapsed or refractory multiple myeloma | 2020 |
| Cetuximab saratolacan | ADC | Cetuximab saratolacan can bind to the epidermal growth factor receptor on the surface of tumor cells, prevent the receptor from binding to other ligands, inhibit the activity of tyrosine kinases, and reduce the transmission of proliferation signals to tumor cells [433] | Head and neck cancer | 2020 |
| Gemtuzumab ozogamicin | ADC | Gemtuzumab ozogamicin is a CD33 antibody drug conjugate (ADC) that, when combined with other enhanced chemotherapy regimens, can reduce disease recurrence and increase the survival of AML patients [50, 434–438] | Acute myeloid leukemia | 2020 |
| Loncastuximab tesirine-lpyl | ADC | When loncastuximab binds to CD19, the linker is degraded by proteases and releases SG3199 within tumor cells. The released SG3199 can bind to small DNA grooves, forming highly cytotoxic DNA strand cross-linking, which subsequently induces tumor cell death [436, 439–441] | Large B-cell lymphoma | 2021 |
| RC48 | ADC | RC48 targets HER2 antigen on the surface of tumor cells, accurately identifying and killing tumor cells, and can cause widespread antigen release to other metastatic lesions [442–444] | HER2+ gastric carcinoma | 2021 |
| Tisotumab vedotin-tftv | ADC | Tisotumab vedotin-tftv is the first TF-guided ADC 1 that works by binding to TFs expressed on solid tumors [445–447] | Cervical cancer | 2021 |
| MIRV | ADC | MIRV enters tumor cells through endocytosis by binding to FRa on the surface of the tumor cell membrane, releases the anti-microtubule drug DM4 under the action of enzymes in tumor cells, and induces cell cycle arrest and apoptosis by inhibiting tubulin polymerization and microtubule aggregation [59, 70, 448–451] | Ovarian cancer | 2022 |
| 111In-DTPA-octreotide | RDC | Octreotide is as a tumor-targeting peptide targeting the somatostatin (SST) receptor, and 111In is a payload that chelates with diethylene triaminopentaacetic acid [452, 453] | Diagnosis of SSTR-positive tumors | 1994 |
| 99mTc-EDDA | RDC | 99mTc-EDDA can be directly used for thyroid imaging or can react with a variety of chelating agents to produce different SPECT imaging agents for different nuclear medicine examination items [454–456] | Diagnostic thyroid imaging | 2013 |
| 68Ga-DOTATATE | RDC | 68Ga DOTATATE is a positron emission tomography (PET) radioactive tracer targeting somatostatin receptor type 2, which has been proven to be a reliable biomarker for meningioma [457–460] | Detection of neuroendocrine cancer | 2016 |
| 177Lu DOTATATE | RDC | 177Lu DOTATATE is a radiation therapy drug that works by binding to specific tumor-expressed somatostatin receptors. After binding to the receptor, the drug enters the cell and causes radiation damage to the tumor cells [461, 462] | Diagnosis of neuroendocrine cancer | 2018 |
| Detectnet | RDC | Detectnet is a positron emission tomography (PET) agent suitable for locating somatostatin receptor-positive neuroendocrine tumors (NETs) in adult patients | Diagnosis of neuroendocrine cancer | 2020 |
| 68 Ga-DOTATOC | RDC | Somatostatin receptor II has become the main target for imaging and treatment of these tumors, and 68 Ga DOTATOC is used in diagnostic imaging for the diagnosis and treatment of NETs [463, 464] | In conjunction with PET, diagnosis of somatostatin receptor-positive neuroendocrine tumors | 2020 |
| 68 Ga-PSMA-11 | RDC | 68 Ga-PSMA-11 PET/CT can be used to evaluate the therapeutic effect and observe the reduction in tumor lesions, especially the invasion of surrounding tissues and organs (rectum, bladder), which has great value in determining subsequent surgical indications [465–468] | Imaging for diagnosis of prostate cancer | 2020 |
| 64Cu DOTATATE | RDC | 64Cu DOTATATE is a radio-diagnostic agent used for positron emission tomography and computed tomography (PET/CT). It can label somatostatin receptor with nuclide to locate neuroendocrine tumors [468–471] | Locating neuroendocrine tumors | 2020 |
| Melflufen | PDC | Because of its high lipophilicity, melflufen can rapidly penetrate cancer cells, hydrolyze aminopeptidase, and effectively induce the intracellular capture of L-PAM to rapidly release alkylating agent into cancer cells [472, 473] | Multiple myeloma, ovarian cancer, breast cancer, acute myeloid leukemia, hematologic imaging | 2021 |
| Illuccix | RDC | The FDA approved Illuccix as a radiometric diagnostic agent with a 68 Ga- radiolabel for PSMA-PET imaging in patients with prostate cancer suspected of metastasis | Treatment of castration-resistant prostate cancer | 2021 |
| LOCAMETZ | RDC | The FDA approved Locametz as a radiometric diagnostic agent for positron emission tomography (PET) of PSMA-positive lesions [474] | Treatment of castration-resistant prostate cancer | 2022 |
| Pluvicto | RDC | The FDA approved Pluvicto for the treatment of PSMA-positive advanced prostate cancer after progression with hormone therapy or chemotherapy | Treatment of castration-resistant prostate cancer | 2022 |