China
Africa
Explore chapters and articles related to this topic
Immunomodulation of Cytokines and T Cells by Biologicals in Rheumatoid Arthritis
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Ravinder N. Maini, Marc Feldmann
Given these interesting data, the question that arises is whether anti-TNF therapy is a form of DMARD that could be effective in long-term control of RA. Since the duration of response to a single infusion of antibody is dose-dependent, lasting a median duration of 3, 6, and 8 weeks after a single infusion of 1, 3, and 10 mg/kg cA2 [69], long-term treatment would require repeated infusions of cA2. In an open study in which seven patients from the first “open label trial” received two or three further repeat cycles of cA2 after relapse of disease, with an observation period, in some cases, extending over a period of more than 1 year. After each sequential infusion, a reproducible clinical response of the same magnitude as the initial infusion was observed [46]. However, there appeared to be a trend toward a shortening of the response period, and in half the patients anti-human chimeric antibody directed against the murine idiotype developed. These results were encouraging in respect to the continuing dominance of TNFα over the cytokine network in RA but were inconclusive in respect to the possibility of continuing therapy. Further clinical trials were necessary to determine the efficacy of repeated therapy with a monoclonal antibody, not yet reported for any clinical indication, and to ascertain whether the immunogenicity of cA2 would be a limiting factor.
The Immunogenicity of Foreign Monoclonal Antibodies in Human Disease Applications: Problems and Current Approaches
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
One of the chimeric antibodies most extensively studied in humans is chimeric 17-1 A, which recognizes a 41 KDa glycoprotein antigen on the surface of gastrointestinal cancer cells (48). This antibody is composed of the variable regions of murine 17-1A and the constant region of a human lgG1 Kappa immunoglobulin. When chimeric 17-1A was administered to colorectal cancer patients, only one patient out of 16 (or 6%) had significant response following the administration of this antibody. In this patient, human anti-lg response was directed primarily against the murine hypervariable regions of the chimeric antibody (49).
Immunoglobulins
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Recombinant DNA techniques are being applied to produce “humanized” antibodies. One method joins mouse variable region genes encoding a particular specificity to human C region genes to create a Chimeric antibody (see Figure 11–5). Another method uses expression of human V genes in bacteria. Colonies can be screened for proteins (antibody fragments) with desired specificities. The genes can then be linked to C genes to create an intact fully human antibody.
B cell depletion and inhibition in systemic lupus erythematosus
Published in Expert Review of Clinical Immunology, 2023
Eugene Krustev, Ann E. Clarke, Megan R.W. Barber
Synergetic B-cell Immunomodulation in SLE (SYNBIoSe) was a phase IIa single arm open label trial that recruited 16 patients with severe (SLEDAI ≥ 12) treatment resistant SLE (including patients with both renal and CNS disease) [98]. In this study, the researchers assessed the efficacy and safety of sequential rituximab (1000 mg IV on weeks 0 and 2) followed by belimumab (10 mg/kg on weeks 4, 6, 8 and then every 4 weeks). This study was primarily focused on assessing the safety and tolerability of this regimen, as well as changes in disease biomarkers (BAFF levels, autoantibody levels, and neutrophil extracellular trap [NET] formation), but also reported clinical improvements as secondary endpoints. Following belimumab treatment, there was a significant reduction in BAFF, anti-dsDNA levels, NET formation, and SLEDAI at week 24. There were 41 adverse events observed and all patients had at least one adverse event. There was a single hospitalization for a serious infectious (self-limited viral gastroenteritis) and 15 minor infections. Other adverse events included human anti-chimeric antibody formation, hypogammaglobulinemia, and viral sinusitis.
Anti-adalimumab Antibodies in Patients with Non-infectious Ocular Inflammatory Disease: A Case Series
Published in Ocular Immunology and Inflammation, 2022
K. Matthew McKay, Nicholas Apostolopoulos, Brian Chou, Thellea K. Leveque, Russell N. Van Gelder
Three patients in this series were transitioned from adalimumab to alternate TNF inhibitors (patients 1, 2 and 6). Patients 1 and 2 were transitioned to infliximab and golimumab, respectively with good effect. Patient 6 developed a paradoxical worsening on transition to golimumab with a ‘cold’ hypopyon, but ultimately achieved good disease control with infliximab. While the ophthalmology literature is lacking, there is good evidence supporting a switch from one anti-TNF therapy to another in the treatment of rheumatologic conditions.25–27 The relative immunogenicity and nature of neutralizing ADAb among these different agents is less well established. One study examined the relative neutralizing and non-neutralizing ADAb response to infliximab, adalimumab, golimumab, and certolizumab.28 The host antibody response to adalimumab and golimumab appears highly restricted to the TNF-binding region of the drug with almost all ADAb resulting in neutralization.28,29 Even for infliximab, a chimeric antibody with murine components in the variable domain, >90% of antibodies appear to be specific for the antigen binding site.28 This suggests a low likelihood of cross-reactivity among antibodies against different anti-TNF agents.
A Novel Class of On-Treatment Cancer Immunotherapy Biomarker: Trough Levels of Antibody Therapeutics in Peripheral Blood
Published in Immunological Investigations, 2022
Yoshinobu Koguchi, William L. Redmond
The presence of an E-R relationship, especially exposure-driven E-R, suggests a potential opportunity to adjust dosing to optimize mAb therapy. This has been most explored in the field of anti-TNF-α therapy, especially infliximab, a chimeric antibody approved by the US FDA in 1998 (Papamichael et al. 2019). The use of infliximab significantly improves symptoms of inflammatory bowel diseases (IBDs). However, a significant proportion of patients experience either a primary failure or a secondary loss of response (LOR) during treatment. Based on this notion, therapeutic drug monitoring (TDM) was introduced to reduce the incidence of LOR by maintaining effective mAb exposure. TDM can be driven by clinical episode (reactive TDM) or scheduled to detect the earliest sign of LOR (proactive TDM) (Shmais et al. 2021). Although dose adjustment based on TDM is still controversial and challenging to implement, improved TDM (e.g., point of care TDM) may facilitate wider implementation and potential benefit particularly for patients with IBDs.