History Of Chronic Dermatitis Research Articles

Abstract PS10-51: TAA013 a trastuzumab antibody drug conjugate phase I dose escalation study in recurrent her2 positive breast cancer

Abstract Background: A phase 1 dose escalation study of TAA013, an antibody drug conjugate linking trastuzumab to a cytotoxic small molecule, DM1, through an SMCC linker, in previously treated recurrent Her2 positive breast cancer patients. Material and Methods: This phase I study follows the traditional 3+3 design, dosing started at 0.6mg/kg, followed by 1.2, 2.4, 3.6, 4.8mg/kg, one intravenous infusion was given every 3 weeks, the initial infusion had to be over 90 minutes, infusion times were later shortened if treatment was well tolerated. The subsequent recommended dose would be expanded to include at least 10 patients. Patients were observed for dose-limiting toxicity (DLT) during a 21-day DLT observation period. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Maximum-tolerated dose (MTD) was defined as the highest dose level that resulted in a DLT in no more than 1 of 6 patients. Study endpoints included safety and tolerability, pharmacokinetic and immunogenicity parameter evaluation, with preliminary evaluation of efficacy. Results: The study enrolled 22 female patients with histologically confirmed Her-2 positive metastatic breast cancer, median age of 50yrs (25-67), median time from initial diagnosis to TAA013 dosing was 39 months (5-99), median prior treatment regimen was 4 (2-10), all had received trastuzumab for a mean of 8.2 months (2-10), alone or in combination with chemotherapy, other prior Her2 targeting drugs given included pertuzumab (2), lapatinib (7), and pyrotinib (8). All patients received at least 2 (median of 6 infusions, range of 1-15) infusions, except for the last 4.8mg/kg patient, but all patients passed the dose limiting toxicity (DLT) observation period of 21 days. There were no dose limiting toxicities, no serious adverse events, nor that resulting in mortality, the maximum tolerated dose was not reached. The most common treatment emergent adverse events (TEAE) included 9 (40.9%) grade 1-2 infusion reactions associated with fever(5) and/or chills(1), the reaction often abated in subsequent cycles. There were no grade 4 TEAE, but there were 3 grade 3 thrombocytopenia, one grade 3 neutropenia, and one grade 3 hyperbilirubinemia which all recovered for the patients to continue treatment, there was also one grade 3 dermatitis in a patient with a history of chronic dermatitis. Antibody drug antibodies were not detected emanating from the TAA013 therapy. Pharmacokinetic studies included evaluation of TAA013, trastuzumab and DM1. Preliminary efficacy evaluation in the 2.4-4.8mg/kg dosing group of heavily pretreated patients resulted in 2 partial responses, including patients who had previously received pyrotinib therapy. Conclusion: TAA013 is a Her2 targeting antibody drug conjugate that is safe and tolerable, with efficacy demonstrated in heavily pretreated Her2 positive breast cancer patients. Keywords: breast cancer, antibody drug conjugates, TAA013. Citation Format: J M Liu, Y M Yin, Hao Wu, W Li, X Huang, XX Li. TAA013 a trastuzumab antibody drug conjugate phase I dose escalation study in recurrent her2 positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-51.

Allergic skin diseases

The skin is one of the largest immunologic organs and is affected by both external and internal factors, as well as innate and adaptive immune responses. Many skin disorders, such as atopic dermatitis, contact dermatitis, urticaria, angioedema, psoriasis, and autoimmune blistering disorders, are immune mediated. Most of these diseases are chronic, inflammatory, and proliferative, in which both genetic and environmental factors play important roles. These immunologic mechanisms might have implications for potential targets of future therapeutic interventions.

Systemic Candida albicans Infection in Two Alpacas ( Lama pacos)

Systemic Candida albicans infection was diagnosed in two adult alpaca stallions originating from different herds. Case 1 had a history of chronic dermatitis with unknown aetiology that had been treated long-term with glucocorticoids. Case 2 had suffered from transient facial paralysis and psoroptic mange of the external ear. Both animals died suddenly after recovering from their initial disorders. Necropsy examination of case 1 revealed multifocal erosive dermatitis, thoracic and abdominal serofibrinous effusions, and multiple suppurative foci in lung, myocardium, kidney, pancreas and brain. Case 2 had multiple ulcers of the third gastric compartment and focal suppurative nephritis. Additionally, moderate depletion of lymphoid organs was observed in both animals. Histologically, suppurative to necrotizing inflammation with necrotizing vasculitis was present in the grossly affected organs of both animals. Yeast, pseudohyphae and branching hyphae were present within these lesions and C. albicans was isolated from lesional tissue of both animals. The primary site of Candida invasion was not determined in case 1, but the most likely portal of entry in case 2 was the gastric ulcers. Depletion of lymphoid tissue suggested a possible underlying immune suppression in both animals.