In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents.

In light of the unprecedented growth in internet usage, safeguarding data from unauthorized access has emerged as a paramount concern. Cryptography and steganography stand as pivotal methods for ensuring data security during transmission. This study introduces an innovative adaptive video steganography approach featuring three tiers of security for extracting concealed information, thereby facilitating secure communication. The embedding process operates within the spatial domain of cover video frames, enabling a remarkable hiding ratio of up to 28.125% (equivalent to 2.25 bits per pixel in payload) without compromising the quality of video frames. Users are afforded the flexibility to select between partial or full embedding capacity of CVF through the proposed adaptive control block (ACB). The chaotic key generator (CKG), which combines a logistic map and sine map, is employed to generate highly sensitive initial seeds for permutation order (PO), frame selection (FS), and random position for hiding (RPH), thereby ensuring three levels of security. Prior to transmission, both CVF and hidden data (SD) are encrypted using PO. Encrypted CVFs are then randomly selected using FS for embedding, with RPH employed during the embedding process. Subsequently, for transmitting the stego-video frame, embedded CVFs are decrypted using the same PO. Experimental results demonstrate the efficacy of the proposed approach, achieving an adaptive hiding ratio ranging from 7.1 to 28.125% (equivalent to 0.56 to 2.25 bits per pixel in payload) and maintaining a peak signal-to-noise ratio (PSNR) within the range of 50.25 to 62.05 dB.

Overloaded trucks have long posed a threat to the road safety. To assess truck payload more effectively, this study focus on tire temperature data obtained through infrared thermal imaging. It is feasible to analyse the payload by monitoring one single representative tire. Tire sidewall surface is the best area for data extraction. Truck overload caused significant increase of gas temperature in tires, as well as external temperature. The internal temperature can be calculated with real gas equation of state. By studying the relationship between internal gas temperature of tire and payload, it is demonstrated that monitoring the temperature of tire sidewall surface is an innovative, remote, and real-time method to assess the payload situation of moving trucks.

The conjugation reaction is the central step in the manufacturing process of antibody-drug conjugates (ADCs). This reaction generates a heterogeneous and complex mixture of differently conjugated sub-species depending on the chosen conjugation chemistry. The parametrization of the conjugation reaction through mechanistic kinetic models offers a chance to enhance valuable reaction knowledge and ensure process robustness. This study introduces a versatile modeling framework for the conjugation reaction of cysteine-conjugated ADC modalities-site-specific and interchain disulfide conjugation. Various conjugation kinetics involving different maleimide-functionalized payloads were performed, while controlled gradual payload feeding was employed to decelerate the conjugation, facilitating a more detailed investigation of the reaction mechanism. The kinetic data were analyzed with a reducing reversed phase (RP) chromatography method, that can readily be implemented for the accurate characterization of ADCs with diverse drug-to-antibody ratios, providing the conjugation trajectories of the single chains of the monoclonal antibody (mAb). Possible kinetic models for the conjugation mechanism were then developed and selected based on multiple criteria. When calibrating the established model to kinetics involving different payloads, conjugation rates were determined to be payload-specific. Further conclusions regarding the kinetic comparability across the two modalities could also be derived. One calibrated model was used for an exemplary in silico screening of the initial concentrations offering valuable insights for profound understanding of the conjugation process in ADC development.

Antibody-drug conjugates (ADCs) represent a promising cancer therapy modality which specifically delivers highly toxic payloads to cancer cells through antigen-specific monoclonal antibodies (mAbs). To date, 15 ADCs have been approved and more than 100 ADC candidates have advanced to clinical trials for the treatment of various cancers. Among these ADCs, microtubule-targeting and DNA-damaging agents are at the forefront of payload development. However, several challenges including toxicity and drug resistance limit the potential of this modality. To tackle these issues, multiple innovative payloads such as immunomodulators and proteolysis targeting chimeras (PROTACs) are incorporated into ADCs to enable multimodal cancer therapy. In this review, we describe the mechanism of ADCs, highlight the importance of ADC payloads and summarize recent progresses of conventional and unconventional ADC payloads, trying to provide an insight into payload diversification as a key step in future ADC development.

BACKGROUND: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs).
METHODS: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials.
RESULTS: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin\'s and lymphoma, Hodgkin\'s), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated.
CONCLUSIONS: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

Antibody-drug conjugates (ADCs) are an emerging class of anticancer agents that combine targeting antibodies with potent cytotoxic agents. Their molecular configuration allows for increased therapeutic efficacy and reduced adverse-effect profiles compared to monoclonal antibodies or cytotoxic chemotherapy alone. ADCs cause off-target toxicities through several mechanisms, including premature deconjugation of the cytotoxic agent in the serum and the presence of the targeted antigen on normal tissues. Given cutaneous adverse events comprise 31.3% of all-grade adverse events in clinical trials involving ADCs, dermatologists are increasingly called upon to manage the cutaneous toxicities caused by these drugs. In this review, we summarize known cutaneous toxicities of the ADCs that have been approved for use by the US Food and Drug Administration to date. Dermatologists can play a key role in recognizing cutaneous reactions associated with ADCs, contributing to guidelines for their management, and aiding during clinical trials to generate detailed morphologic and histopathologic descriptions of cutaneous toxicities caused by ADCs.

BACKGROUND: Antibody drug conjugates represent a promising class of antineoplastic agents comprised of a monoclonal antibody linked to a potent cytotoxic payload for targeted delivery of chemotherapy to tumors. Various antibody drug conjugates have demonstrated impressive efficacy in patients with metastatic urothelial carcinoma in clinical trials, leading to two FDA approved therapies and several other agents and combinations in clinical development.
METHODS: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens.
RESULTS: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable.
CONCLUSIONS: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.

Antibody-drug conjugates (ADCs) provide effective cancer treatment through the selective delivery of cytotoxic payloads to the cancer cells. They offer unparalleled precision and specificity in directing drugs to cancer cells while minimizing off-target effects. Despite several advantages, there is a requirement for innovations in the molecular design of ADC owing to drug resistance, cancer heterogeneity along the adverse effects of treatment. The review critically analyses ADC function mechanisms, unraveling the intricate interplay between antibodies, linkers, and payloads in facilitating targeted drug delivery to cancer cells. The article also highlights notable advancements in antibody engineering, which aid in creating highly selective and potent ADCs. Additionally, the review details significant progress in clinical ADC development with an in-depth examination of pivotal trials and approved formulations. Antibody Drug Conjugates (ADCs) are a ground-breaking approach to targeted drug delivery, especially in cancer treatment. They offer unparalleled precision and specificity in directing drugs to cancer cells while minimizing off-target effects. This review provides a comprehensive examination of the current state of ADC development, covering their design, mechanisms of action, and clinical applications. The article emphasizes the need for greater precision in drug delivery and explains why ADCs are necessary.

As the development of new biotherapeutics advances, increasingly sophisticated tandem mass spectrometry methods are needed to characterize the most complex molecules, including antibody drug conjugates (ADCs). Lysine-linked ADCs, such as trastuzumab-emtansine (T-DM1), are among the most heterogeneous biotherapeutics. Here, we implement a workflow that combines limited proteolysis with HCD-triggered EThcD and UVPD mass spectrometry for the characterization of the resulting middle-down large-sized peptides of T-DM1. Fifty-three payload-containing peptides were identified, ranging in mass from 1.8 to 16.9 kDa, and leading to the unambiguous identification of 46 out of 92 possible conjugation sites. In addition, seven peptides were identified containing multiple payloads. The characterization of these types of heterogeneous peptides represents an important step in unraveling the combinatorial nature of lysine-conjugated ADCs.