1. Introduction

Figure 1. Schematic of ADC structure and functionality with potential for high-scale engineering and specific cell targeting and destruction. A) Antibody binding to antigens with high specificity and internalization of the complex. B) Schematic overview of linker structure with binding of antibody to the cytotoxic payload. C) Revealing how toxicity occurs through payload internalization, linker cleavage, and molecular activities inducing cell death. D) Different immune effector functions induced by the Fc region engage cells and induce cellular responses based on the payload mechanism[3].

Figure 1. Schematic of ADC structure and functionality with potential for high-scale engineering and specific cell targeting and destruction. A) Antibody binding to antigens with high specificity and internalization of the complex. B) Schematic overview of linker structure with binding of antibody to the cytotoxic payload. C) Revealing how toxicity occurs through payload internalization, linker cleavage, and molecular activities inducing cell death. D) Different immune effector functions induced by the Fc region engage cells and induce cellular responses based on the payload mechanism[3].

Figure 2. An overview of ADC structure, with monoclonal antibody regions, a stable linker, and a potent cytotoxic payload that delivers specificity and toxicity to cancer cells[4].

Figure 2. An overview of ADC structure, with monoclonal antibody regions, a stable linker, and a potent cytotoxic payload that delivers specificity and toxicity to cancer cells[4].

2. Methods

Figure 3. A systematic approach to review with methods in accordance with PRISMA guidelines. This involves reports excluded due to irrelevance to our study, a lack of pharmacological data, or out of scope interventions. No Automation tools were used and databases utilized include Drugbank, Pubmed, Google Scholar, and Medline[38,39].

Figure 3. A systematic approach to review with methods in accordance with PRISMA guidelines. This involves reports excluded due to irrelevance to our study, a lack of pharmacological data, or out of scope interventions. No Automation tools were used and databases utilized include Drugbank, Pubmed, Google Scholar, and Medline[38,39].

3. ADC Engineering Approaches

3.1. Antigen Binding

ADCs target specific antigens on cancer cells, including HER2, trop2, nectin4, and EGFR in solid tumors, and CD19, CD22, CD33, CD30, BCMA, and CD79b in hematological malignancies(blood cancers and malignancies)[6]. The targeting of these antigens ensures that the cytotoxic payload is delivered directly to cancer cells, minimizing damage to healthy cells. Additionally, some ADCs are designed to target components of the tumor microenvironment, such as the vasculature or stroma, which can also contribute to the efficacy of the treatment[7]. In the development of Antibody-Drug Conjugates (ADCs), the selection of the target antigen on tumor cells is a critical step, acting as the guiding beacon for the ADCs to accurately identify and target tumor cells[4]. This choice is pivotal because it dictates how the cytotoxic payloads are delivered into the cancer cells, commonly via mechanisms such as endocytosis. The ideal target antigen for ADC therapy should have a high expression specifically on tumor cells, with little to no presence in normal tissues, to minimize the risk of off-target effects and maximize the safety of the treatment. These antigens should be located on the surface or extracellular part of the tumor cells, making them accessible to the circulating ADCs[7]. Additionally, the target antigens should not be secretory to prevent undesirable ADC binding outside the tumor sites, which could reduce the efficacy of tumor targeting and raise safety concerns. Moreover, it is advantageous if these antigens can be internalized upon binding with the ADC, as this facilitates the entry of the ADC-antigen complex into the cancer cells, followed by the appropriate intracellular transport and release of the cytotoxic payload[4,6,7]. The ongoing research in oncology and immunology has broadened the horizons for ADC target antigens, extending beyond conventional tumor cell antigens to targets within the tumor microenvironment, such as the stroma and vasculature. This expansion in target selection is based on the emerging evidence that targeting these areas can significantly enhance the effectiveness of ADCs. For instance, targeting the matrix within the tumor environment could disrupt the concentration of growth factors vital for cancer cell survival, which often relies on angiogenesis and matrix factors. Targeting these more genetically stable cells in the tumor microenvironment also presents a potential strategy to mitigate the risk of mutation-induced drug resistance. This evolution in the approach to targeting reflects a more comprehensive strategy in ADC development, aiming to encompass a broader range of elements within the tumor microenvironment for more effective cancer therapy. With greater knowledge of Antigen targets and network interactions of downstream protein effects, these antigen-binding sites can be changed or manipulated to mitigate the downstream symptomatic effects of these highly cytotoxic drugs. Through a rigorous engineering approach of monoclonal antibody selection for highly specific interactions primarily with cancer tumor cells, a higher efficacy and safety profile can be reached for these drugs[4,7,8].

Figure 4. An overview of mechanistic action of ADCs from blood circulation to apoptotic activities. Each ADC will bind to different receptors on the cell surface and be internalized with different mechanisms. After internalization, there are several pathways of cell destruction including DNA or microtubule interference causing cell destruction potential[4].

Figure 4. An overview of mechanistic action of ADCs from blood circulation to apoptotic activities. Each ADC will bind to different receptors on the cell surface and be internalized with different mechanisms. After internalization, there are several pathways of cell destruction including DNA or microtubule interference causing cell destruction potential[4].

3.4. Cytotoxic Payload Specifications

In the realm of cancer therapy, antibody-drug conjugates (ADCs) represent a significant advancement, with the cytotoxic payload being the critical component responsible for the destruction of cancer cells upon internalization. These payloads, due to the limited efficiency of ADC delivery to tumor sites, demand high potency, often reflected in IC50 values ranging in the nanomolar to picomolar scale. ADCs typically utilize various cytotoxic agents, broadly categorized into tubulin inhibitors, DNA damaging agents, and the emerging class of immunomodulators. Tubulin inhibitors, like auristatin and maytansinoid derivatives, disrupt cell division by targeting microtubule functions. DNA damaging agents, including calicheamicin and pyrrolobenzodiazepines, induce lethal DNA damage in cancer cells. The newest category, immunomodulators, aims to stimulate the immune system, thereby enhancing tumor regression and sustained anti-tumor immunity, with TLR and STING agonists being notable examples. A promising development in this area is ISACs (immunestimulating antibody conjugates), which merge precise antibody targeting with the immunomodulatory impact of small molecule payloads, exemplified by BDC-1001 and CRD5500[7–9].

The incorporation of novel payloads with unique mechanisms is expanding ADC applications, potentially offering enhanced efficacy and reduced side effects in cancer treatment. Notably, ADCs have a significantly larger molecular weight than conventional cytotoxic drugs, which may restrict their tumor penetration efficiency. The research underscores that only a fraction of administered ADCs reach tumor cells, thus emphasizing the necessity for potent payloads in ADC design. Delivery of these payloads hinges on the internalization of the ADC-antigen complex, either via antigen-dependent endocytosis or antigenindependent pinocytosis. Following internalization, the complex is transported to endosomes or lysosomes, where payloads are released, depending on the nature of their linkers and the specific intracellular environment. Importantly, some ADCs exhibit a ”bystander effect,” impacting neighboring cancer cells that lack the target antigens. This effect is particularly vital for ADCs aimed at tumors with varied antigen expression and relies on the ability of the released payload to permeate cell membranes, favoring nonpolar over polar molecules due to their higher likelihood of cell membrane crossing[6,8,9].

Traditional payloads are primarily chemotherapeutic drugs, microtubule inhibitors, and DNAdamaging elements. However, with relatively low therapeutic indexes, these drugs can be optimized or other investigational pathways could be investigated to mitigate these side effects, therefore optimizing payload capabilities. Currently, payloads consist of mechanisms involving microtubule targeting, Maytansinoids, Auristatin, Eribulin, Tubulysins, Cryptophycins, EG5 inhibitors, DNA targeting payloads, Enediyne, Topoisomerase I inhibitors, PBD, Duocarmycins, RNA targeting payloads, Thailanstatin, Amatoxins, immune ADC payloads, toll-like receptor agonists, STING agonists, and Glucocorticoid receptor modulators all with differing therapeutic indices. Several new alternative payloads are being investigated across different classes with highly prominent pathways being bcl-xL inhibitors, NAMPT inhibitors, Carmaphycins, PROTAC payloads, NIRPIT drug payloads, and dual payload combination therapies. Moreover, the development of a PDC or peptide drug conjugate has greater advantages like lower molecular weight, higher tumor penetration, high biocompatibility, lower manufacturing costs, and greater uniformity across synthesization[8].

Figure 5. This figure outlines current cytotoxic payload capabilities, with potential expansionary investigations into RNA inhibition, and immunologicaloriented payloads, along with several other potential advancements. Optimizing the payload can lead to future mitigations of side effects and greater apoptotic potential within cancer cells[8].

Figure 5. This figure outlines current cytotoxic payload capabilities, with potential expansionary investigations into RNA inhibition, and immunologicaloriented payloads, along with several other potential advancements. Optimizing the payload can lead to future mitigations of side effects and greater apoptotic potential within cancer cells[8].

3.5. Mechanisms and Effector Functions

Antibody-drug conjugates (ADCs) play a dual role in cancer therapy, serving as precision-guided ”biological missiles”[2] that offer specific targeting capabilities coupled with potent effects in killing cancer cells. This approach notably improves the therapeutic window and diminishes off-target side effects. The primary mechanism of ADCs involves several crucial steps. Initially, the monoclonal antibody (mAb) component binds to antigens specifically expressed on cancer cells, followed by the internalization of the ADC through endocytosis. This process transitions from early endosomes to late endosomes, and ultimately to fusion with lysosomes.

Within the lysosomes, cytotoxic payloads are released via chemical or enzyme-mediated mechanisms, targeting vital cellular components such as DNA or microtubules and leading to cell death or apoptosis. If the payload can cross cell membranes, it may also induce a bystander effect, thereby enhancing the ADC’s efficacy by affecting neighboring cancer cells. In addition to direct cytotoxicity, ADCs exert anticancer effects through various mechanisms. These include Antibody-Dependent Cellular Cytotoxicity (ADCC), where the antibody’s Fab segment binds to cancer cell antigens, and the Fc segment interacts with immune effector cells, resulting in direct cell killing. Antibody-dependent cellular Phagocytosis (ADCP) involves immune cells, particularly macrophages, engulfing cancer cells coated with ADCs, aiding in tumor clearance. Complementdependent cytotoxicity (CDC) is triggered when antibodies on cancer cell surfaces activate the complement system, leading to cell lysis. Furthermore, ADCs can inhibit downstream signaling pathways essential for cell survival and proliferation, such as the inhibition of signal transduction pathways like PI3K or MAPK by the antibody component in T-DM1, which targets HER2 receptors, ultimately inducing apoptosis. Overall, ADCs utilize a multifaceted strategy in combating cancer, combining the targeted delivery of cytotoxic payloads with immune-mediated mechanisms and inhibition of critical signaling pathways in cancer cells. This comprehensive approach underscores the versatility and effectiveness of ADCs in cancer therapy[2,6,7].

Figure 6. A general overview of mechanisms of ADCs for killing cancer cells(Upper-Right); CDC, ADCC, ADCC effects of eliciting antitumor immunity(Lower Left); Antibody component retains activity profile and can interfere with target functionality, dampening downstream signaling, inhibiting tumor growth(Lower Right)[2].

Figure 6. A general overview of mechanisms of ADCs for killing cancer cells(Upper-Right); CDC, ADCC, ADCC effects of eliciting antitumor immunity(Lower Left); Antibody component retains activity profile and can interfere with target functionality, dampening downstream signaling, inhibiting tumor growth(Lower Right)[2].

4. ADC Drug Classifications and Review

4.1. Adcetris(Brentuximab Vedotin)

Brentuximab vedotin, marketed under the brand name ADCETRIS, stands as a pivotal intravenous antibody-drug conjugate (ADC) particularly effective against CD30-positive cancer cells, with a significant impact on classical Hodgkin lymphoma (HL). Brentuximab vedotin is a chimeric immunoglobulin G1 antibody-drug conjugate targeting CD30, linked to monomethyl auristatin E (MMAE) through a protease-cleavable linker. It effectively induces apoptotic death in CD30-expressing tumor cells by binding to their surface[9]. This ADC has shown high objective response rates in patients with relapsed or refractory CD30-positive HL, evidenced by clinical trials and real-world applications, including scenarios where retreatment is necessary[9]. From a pharmacokinetic perspective, data derived from phase 1 trials and population analysis involving 314 patients revealed that brentuximab vedotin and its antibody component share similar profiles. Its maximum serum concentrations are usually reached near the end of a 30-minute infusion, while MMAE peaks between 1 to 3 days later[10]. Dose-proportional exposure and minimal accumulation over multiple doses were noted, with steady-state achieved within 21 days of each 3-week dose. MMAE exposure declines to about 50-80 percent with continued administration. Notably, as a consolidation therapy following autologous hematopoietic stem cell transplant (ASCT), brentuximab vedotin has substantially extended progression-free survival compared to a placebo, with these benefits persisting during extended follow-up periods[9,11,12].

The safety profile of brentuximab vedotin has been deemed acceptable in both controlled trials and realworld settings. In March 2018, the FDA approved Adcetris (brentuximab vedotin) for treating adult patients with previously untreated stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. This approval broadened its therapeutic use, adding to its existing approvals for Hodgkin’s lymphoma post-relapse or post-stem cell transplantation, systemic anaplastic large cell lymphoma after other treatments failed, and primary cutaneous ALCL following unsuccessful treatments. Lymphoma originates in the lymphatic system, with Hodgkin lymphoma having two main types, most commonly the classical type characterized by ReedSternberg cells. The ECHELON-1 study showed Adcetris combined with chemotherapy improved efficacy compared to previous standards, notably eliminating the highly toxic agent bleomycin from the regimen, signifying significant advancement in treatment. The most common manageable adverse events include peripheral sensory neuropathy and neutropenia. Given the limited range of treatment options available for relapsed or refractory HL, brentuximab vedotin emerges as a vital therapeutic choice. It is especially relevant for patients who have not responded to high-dose chemotherapy/ASCT or those who have undergone multiple prior chemotherapy treatments. Furthermore, its use as post-ASCT consolidation therapy offers a promising option for highrisk patients, underscoring its significance in the landscape of HL treatment[10–12].

Figure 7. Mechanism of action of Brentuximab Vedotin in CD-30 positive tumor cell. 1)Adcetris binds to the CD30 membrane target receptor. 2) drug complex internalized by a lysosome and enzymes cleave the linker between monoclonal antibody and cytotoxic payload MMAE. 3) MMAE is released within the cell where it binds to tubulin inducing apoptosis[11].

Figure 7. Mechanism of action of Brentuximab Vedotin in CD-30 positive tumor cell. 1)Adcetris binds to the CD30 membrane target receptor. 2) drug complex internalized by a lysosome and enzymes cleave the linker between monoclonal antibody and cytotoxic payload MMAE. 3) MMAE is released within the cell where it binds to tubulin inducing apoptosis[11].

4.2. Kadcyla(Trastuzumab Emtansine)

Breast cancer (BC) is a common disease globally and presents substantial public health challenges. Recent advances in molecular biology and immunotherapy have led to targeted treatments based on specific patient and disease profiles[10]. A key element in BC pathophysiology is the overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), which is also a critical biomarker for therapy selection. Trastuzumab, a recombinant igG1 humanized monoclonal antibody that targets HER2, was the first biologic drug approved for treating HER2-positive BC and continues to be a cornerstone of therapy, even with the emergence of other anti-HER2 agents like pertuzumab and lapatinib. However, issues such as cardiotoxicity and resistance to treatment have been noted, and there remains a lack of consistent resolution on various therapeutic aspects in existing literature. Therefore, a thorough review of trastuzumab is necessary to equip clinicians with vital information regarding its pharmacokinetics, pharmacodynamics, clinical usage, and ongoing setbacks/ symptomatic responses[10,13].

HER2, part of the tyrosine kinase receptor family, is essential in both normal and malignant breast tissues, activated through dimerization with other HER family members like HER1 (EGFR), HER3, and HER4, rather than ligand-binding. In breast cancer (BC), 15-30 percent of cases exhibit HER2 overexpression, categorizing them as HER2-positive, a subtype linked to increased tumorigenicity due to constant activation of downstream signaling pathways. This overexpression is associated with a more aggressive BC phenotype, marked by rapid tumor growth, early metastasis, and reduced survival rates. Trastuzumab, a monoclonal antibody targeting HER2, has revolutionized HER2-positive BC treatment but is contingent on HER2 overexpression. Determining HER2 status, crucial in BC management, is conducted through immunohistochemical analysis or in situ hybridization, with borderline cases retested to guide treatment decisions, highlighting the importance of understanding and accurately assessing HER2 in tailoring effective breast cancer therapies[13,14].

Figure 8. Mechanism of action of Trastuzumab Emtansine. This drug has an ADCC induction profile undergoing antibody-dependent cellular cytotoxicity. It binds to subdomain IV of the HER2 receptor, leading to receptor-mediated internalization with concurrent endosomal/lysosomal intake and linker degradation releasing DM1-containing cytotoxic catabolites[13].

Figure 8. Mechanism of action of Trastuzumab Emtansine. This drug has an ADCC induction profile undergoing antibody-dependent cellular cytotoxicity. It binds to subdomain IV of the HER2 receptor, leading to receptor-mediated internalization with concurrent endosomal/lysosomal intake and linker degradation releasing DM1-containing cytotoxic catabolites[13].

Trastuzumab emtansine, a hydrophilic molecule, operates by binding to the HER2 receptor’s subdomain IV and undergoing receptor-mediated internalization via endocytosis[15]. It follows the endosomallysosomal pathway, where it degrades to release DM1-containing cytotoxic catabolites. DM1, a positively charged molecule linked to lysine, disrupts microtubule assembly, leading to cell cycle arrest and apoptotic death. This drug maintains the antitumor efficacy of trastuzumab, with a similar affinity for HER2-expressing cells. It not only mediates antibody-dependent cell-mediated cytotoxicity but also hinders HER2 extracellular domain shedding and blocks HER3 phosphorylation, thereby impeding the PI3K pathway. Targeting HER2-positive cells selectively, trastuzumab emtansine is more potent than trastuzumab alone. Additionally, it disrupts epithelial-to-mesenchymal transition and reduces the clonogenic potential of cancer stem cells. Resistance to trastuzumab emtansine can develop, potentially due to the upregulation of multi-drug resistance transporters or increased expression of EGFR and other receptors[13–15].

4.7. Mylotarg (Gemtuzumab Ozogamicin)

Gemtuzumab ozogamicin (GO), an antibody-drug conjugate targeting CD33 linked to the toxin calicheamicin, was initially FDA-approved in 2000 for CD33+ acute myeloid leukemia (AML). However, it was withdrawn due to efficacy concerns and increased hepatotoxicities, including hepatic venoocclusive disease (VOD), as observed in the SWOG0106 study. Subsequent research, including the ALFA-0701 study, showed that lower, fractionated doses of GO combined with standard chemotherapy (SC) led to improved survival and reduced toxicities. A meta-analysis across five phase 3 studies confirmed these benefits, with a 3 mg/m2 dose associated with lower hepatoxicity than the 6 mg/m2 dose, culminating in GO’s 2017 reapproval for treating CD33+ AML[13]. Gemtuzumab ozogamicin, a recombinant humanized IgG4 kappa antibody conjugated with calicheamicin, a cytotoxic antitumor antibiotic derived from Micromonospora echinospora ssp. calichensis targets the CD33 antigen found on leukemic myeloblasts in most acute myeloid leukemia (AML) patients. About 50 percent of the antibody carries 4-6 moles of calicheamicin per mole of antibody, focusing on inhibiting growth and inducing cell death in cancerous cells. Initially approved by the FDA in 2000 for CD33-positive AML in the first relapse in patients 60 years or older not suited for cytotoxic chemotherapy, it was withdrawn in 2010 due to safety concerns and insufficient clinical benefit. However, following reassessment and adaptation of dosing regimens, it was reapproved in 2017 for adults with newly diagnosed CD33-positive AML, in combination with chemotherapy or as monotherapy, and for patients aged 2 years and older with relapsed or refractory CD33-positive AML[13,26].

Figure 9. A representative example of Mylotarg molecularly with Gemtuzumab monoclonal antibody bound with a linker to small molecule N-acetyl calicheamicin. This follows a similar pattern of ADC structures represented through a monoclonal antibody bound to a linker and cytotoxic component[25].

Figure 9. A representative example of Mylotarg molecularly with Gemtuzumab monoclonal antibody bound with a linker to small molecule N-acetyl calicheamicin. This follows a similar pattern of ADC structures represented through a monoclonal antibody bound to a linker and cytotoxic component[25].

4.10. Zynlonta(Loncastuximab Tesirine)

CD19, a key antigen in B-cell malignancies, presents an ideal target for antibody-drug conjugates (ADCs), particularly in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common subtype of B-cell non-Hodgkin lymphoma. Standard front-line treatment is R-CHOP resulting in a cure 60-65% of the time. Many patients that are r/r have poor prognoses, necessitating alternative therapies as approximately 40% of frontline treatments fail. Loncastuximab tesirine, a novel ADC comprising a humanized igG1, anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer warhead, was approved by the FDA in 2021 for r/r DLBCL after two or more systemic therapies[34]. It works by binding to CD19 on B-cells, facilitating internalization and release of the cytotoxic payload SG3199, which forms DNA crosslinks, leading to cell death. This drug has exhibited the bystander-killing effect meaning it also induces cell death in neighboring CD19Cells showing potentially high therapeutic efficacy. This therapy addresses the critical need for effective treatments in r/r DLBCL, where standard therapies and CAR T-cell options have limitations in efficacy, safety, and accessibility[34].

Loncastuximab Tesirine shows antitumor activity against malignant B-cells, but higher exposure during the first therapy cycle is associated with an increased occurrence of Grade 2 adverse reactions. Administered intravenously, loncastuximab tesirine has a Cmax of 2995 g/L in Cycle 1 and 3155 g/L in Cycle 2, with an AUC ranging from 15,245 to 22,823 g*day/L. Its average distribution volume is around 7.11 liters, and while protein binding data are lacking, the antibody part is broken down into peptides, and SG3199 is metabolized by CYP3A4/5. SG3199’s excretion pathways in humans are not fully understood but are believed to be minimally renal. The halflife of loncastuximab tesirine-lpyl ranges from 7.06 to 12.5 days, with its clearance decreasing over time. However, higher doses can lead to increased toxicity and potential discontinuation of the drug[34–36].

Figure 10. Mechanism of action of Loncastuximab Tesirine. Lonca binds to the CD19 antigen on the tumor cell surface the ADC is internalized and the cytotoxic payload is released with free PBD dimers binding the minor groove of cell DNA causing apoptosis[35].

Figure 10. Mechanism of action of Loncastuximab Tesirine. Lonca binds to the CD19 antigen on the tumor cell surface the ADC is internalized and the cytotoxic payload is released with free PBD dimers binding the minor groove of cell DNA causing apoptosis[35].

5. Discussion and Further Analysis

References

1. Khongorzul, P., Ling, C. J., Khan, F. U., Ihsan, A. U., & Zhang, J. (2020). Antibody–Drug Conjugates: A Comprehensive Review. Molecular Cancer Research, 18(1), 3–19. [CrossRef]
2. Fu, Z., Li, S., Han, S. et al. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Sig Transduct Target Ther 7, 93 (2022). [CrossRef]
3. Hoffmann, R. M., Coumbe, B. G. T., Josephs, D. H., et al. Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs). Oncoimmunology, 2017 Nov 20;7(3):e1395127. [CrossRef]
4. Peters, C., & Brown, S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep, 2015 Jun 12;35(4):e00225. [CrossRef]
5. Pharmaceutical Technology. (2023, January 6). Who are the leading innovators in antibody drug conjugates (ADC) cancer therapy for the pharmaceutical industry? https://www.pharmaceutical-technology.com/data-insights/.
6. Scott, L. J. (2017). Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Drugs, 77(4), 435–445. [CrossRef]
7. DrugBank. (n.d.). Brentuximab vedotin: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB08870.
8. Maximiano, S., Magalh˜aes, P., Guerreiro, M. P., & Morgado, M. (2016). Trastuzumab in the Treatment of Breast Cancer. BioDrugs, 30(2), 75–86. [CrossRef]
9. Dhillon, S. (2014). Trastuzumab emtansine: a review of its use in patients with HER2positive advanced breast cancer previously treated with trastuzumab-based therapy. Drugs, 74(6), 675–686. https://doi.org/10.1007/innovators-antibody-drug-conjugates-adc-cancers-4t0h2e6r5a-p0y1-4p-h0a2r0m1a-c0eutical.
10. Riccardi, F., Dal Bo, M., Macor, P., Toffoli, G. A comprehensive overview on antibodydrug conjugates: from the conceptualization to cancer therapy. Front Pharmacol, 2023 Sep 18;14:1274088. [CrossRef]
11. Shastry, M. et al. Rise of Antibody-Drug Conjugates: The Present and Future. Am Soc Clin Oncol Educ Book 43, e390094 (2023). [CrossRef]
12. Wang, Z., Li, H., Gou, L., Li, W., Wang, Y. Antibody–drug conjugates: Recent advances in payloads. Acta Pharmaceutica Sinica B, Volume 13, Issue 10, 2023, Pages 4025-4059. [CrossRef]
13. Zhao, M. K. (2017). Monoclonal Antibodies. In Reference Module in Life Sciences, Book chapter: Antibody drug Conjugates beyond cytotoxic payloads. Elsevier. https://www.sciencedirect.com/topics/neuroscience/antibody-drug-conjugate.
14. DrugBank. (n.d.). Trastuzumab: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB00072.
15. Markham, A. Belantamab Mafodotin: First Approval. Drugs. 2020 Oct;80(15):16071613. [CrossRef]
16. DrugBank. (n.d.). Belantamab mafodotin: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB15719.
17. Lee, J., & Park, Y. H. Trastuzumab deruxtecan for HER2+ advanced breast cancer. Future Oncol. 2022 Jan;18(1):7-19. [CrossRef]
18. DrugBank. (n.d.). Trastuzumab deruxtecan: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB14962.
19. Syed, Y. Y. Sacituzumab Govitecan: First Approval. Drugs. 2020 Jul;80(10):10191025. [CrossRef]
20. DrugBank. (n.d.). Sacituzumab Govitecan: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB12893.
21. Sehn, L. H., Herrera, A. F., Flowers, C. R., et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. [CrossRef]
22. Raqib, M. A., Haseeb, A., Shafique, M. A., et al. (2023) Advances in Polatuzumab Vedotin-PIIQ Therapy: A Review of Treatment Efficacy in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma, Pediatric Health, Medicine and Therapeutics, 14:, 323-331. [CrossRef]
23. Polivy. Available online: www.polivy.com/content/dam/gene/polivy/patient/en_us/rrdlbcl/pdfs/polivy-3l-patient-brochure.pdf Accessed 1 Apr. 2024.
24. Swaminathan, M., & Cortes, J. E. Update on the role of gemtuzumab-ozogamicin in the treatment of acute myeloid leukemia. Ther Adv Hematol. 2023 Feb 9;14:20406207231154708. [CrossRef]
25. DrugBank. (n.d.). Gemtuzumab ozogamicin: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB00056.
26. Al-Salama, Z. T. Inotuzumab Ozogamicin: A Review in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia. Targ Oncol, 13, 525–532 (2018). [CrossRef]
27. Yurkiewicz, I. R., Muffly, L., & Liedtke, M. Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Drug Des Devel Ther. 2018 Jul 24;12:2293-2300. [CrossRef]
28. DrugBank. (n.d.). Inotuzumab ozogamicin: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB05889.
29. Dhillon, S. Moxetumomab Pasudotox: First Global Approval. Drugs. 2018 Nov;78(16):1763-1767. [CrossRef]
30. DrugBank. (n.d.). Moxetumomab pasudotox: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB12688.
31. Ryan, C. (2023, January 13). AstraZeneca to Discontinue Moxetumomab Pasudotox in US for Hairy Cell Leukemia. OncLive. https://www.onclive.com/view/astrazeneca-to-discontinue-moxetumomab-pasudotox-in-u.
32. Medthority. (2023, January 14). AstraZeneca to discontinue selling Lumoxiti in the US due to low clinical uptake. Retrieved from https://www.medthority.com/news/2023/1/astrazeneca-to-discontinue-selling-lumoxiti-in-the-us.
33. Xu, B. Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Eur J Clin Pharmacol. 2022 May;78(5):707-719. [CrossRef]
34. Furqan, F., & Hamadani, M. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. Ther Adv Hematol. 2022 Mar 22;13:20406207221087511. [CrossRef]
35. DrugBank. (n.d.). Loncastuximab tesirine: Uses, Interactions, Mechanism of Action. Retrieved from https://go.drugbank.com/drugs/DB16222.
36. MarketsandMarkets. (2023). Antibody Drug Conjugates (ADC) Market by Product, Linker Type, Payload Type, Target, Disease, Region Global Forecast to 2028 (Report No. BT 8808). https://www.marketsandmarkets.com/Market-Reports/antibody-drug-conjugates-market-122857391.html.
37. Haddaway, N. R., Page, M. J., Pritchard, C. C., & McGuinness, L. A. (2022). PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis Campbell Systematic Reviews, 18, e1230. [CrossRef]
38. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372:n71. [CrossRef]