Antibody‑drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small‑molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first‑generation ADC. Since then, at least 100 ADC‑related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization strategies for the next generation of drugs. Subsequently, experts have improved the first‑generation ADCs and have developed second‑generation ADCs such as ado‑trastuzumab emtansine. Second‑generation ADCs have higher specific antigen levels, more stable linkers and longer half‑lives and show great potential to transform cancer treatment models. Since the first two generations of ADCs have served as a good foundation, the development of ADCs is accelerating, and third‑generation ADCs, represented by trastuzumab deruxtecan, are ready for wide application. Third‑generation ADCs are characterized by strong pharmacokinetics and high pharmaceutical activity, and their drug‑to‑antibody ratio mainly ranges from 2 to 4. In the past decade, the research prospects of ADCs have broadened, and an increasing number of specific antigen targets and mechanisms of cytotoxic drug release have been discovered and studied. To date, seven ADCs have been approved by the FDA for lymphoma, and three have been approved to treat breast cancer. The present review explores the function and development of ADCs and their clinical use in cancer treatment.
Background: Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases. Purpose: To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients. Methods: Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies. Results: 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml. Conclusion: Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.
13 May 2023 in Archives of Dermatological Research
Background: Melasma is a chronic hypermelanosis requiring effective therapies. Methods: This prospective, randomized controlled trial evaluated intense pulsed light (IPL) and topical tranexamic acid (TXA) versus IPL with placebo. Thirty-three patients completed the 5-month study (group A: TXA + IPL, n = 17; group B: Placebo + IPL, n = 16). Outcome included VISIA analysis, modified Melasma Area and Severity Index (mMASI), skin melanin index (MI) and erythema index (EI) measurement. Results: At Month 5, both groups showed improved mMASI scores; however, group A demonstrated a significantly greater reduction than group B (−50.52% vs. −38.49%; mean difference −12.03%, 95% CI −23.74% to −0.32%; p < 0.05). Excellent improvement was achieved in 70.59% of Group A versus 25% of Group B. Furthermore, Group A exhibited a significant decrease in MI (−36.31%) compared to a negligible change in Group B (−1.28%), with a significant between-group difference (p = 0.02). VISIA analysis confirmed superior improvements in brown spots and texture for Group A (p < 0.05). No adverse events occurred. Conclusions: Combining topical TXA with IPL is a safe and significantly more effective treatment for melasma than IPL alone, offering superior pigment reduction without increased risks.