Immune regulatory adjuvant approach to mitigate subcutaneous immunogenicity of monoclonal antibodies.

Introduction: Immunogenicity continues to be a challenge for development and clinical utility of monoclonal antibodies, and there are gaps in our current ability to prevent anti-drug antibody development in a safe and antigen-specific manner.

Methods: To mitigate immunogenicity of monoclonal antibodies administered subcutaneously, O-phospho-L-serine (OPLS)-the head group of the tolerance-inducing phospholipid, phosphatidylserine-was investigated as an immunoregulatory adjuvant.

Results: Formulations of adalimumab, trastuzumab or rituximab with OPLS showed reduction in relative immunogenicity in mice compared to vehicle formulations, indicated by reduced anti-drug antibody development and significant reductions in CD138+ plasma cell differentiation in bone marrow.

Rating pome fruit quality traits using deep learning and image processing.

Quality assessment of pome fruits (i.e. apples and pears) is used not only for determining the optimal harvest time but also for the progression of fruit-quality attributes during storage.

Immunogenicity of Therapeutic Biological Modalities - Lessons from Hemophilia A Therapies.

The introduction and development of biologics such as therapeutic proteins, gene-, and cell-based therapy have revolutionized the scope of treatment for many diseases. However, a significant portion of the patients develop unwanted immune reactions against these novel biological modalities, referred to as immunogenicity, and no longer benefit from the treatments. In the current review, using Hemophilia A (HA) therapy as an example, we will discuss the immunogenicity issue of multiple biological modalities.

Phosphatidylserine-mediated oral tolerance.

Phosphatidylserine (PS) is an anionic phospholipid exposed on the surface of apoptotic cells. The exposure of PS typically recruits and signals phagocytes to engulf and silently clear these dying cells to maintain tolerance via immunological ignorance. However, recent and emerging evidence has demonstrated that PS converts an "immunogen" into a "tolerogen", and PS exposure on the surface of cells or vesicles actively promotes a tolerogenic environment.

Biophysical Characterization of Tolerogenic Lipid-Based Nanoparticles Containing Phosphatidylcholine and Lysophosphatidylserine.

Autoimmune conditions, allergies, and immunogenicity against therapeutic proteins are initiated by the unwanted immune response against self and non-self proteins. The development of tolerance induction approaches can offer an effective treatment modality for these clinical conditions. We recently showed that oral administration of lipidic nanoparticles containing phosphatidylcholine (PC) and lysophosphatidylserine (Lyso-PS) converted an immunogen to a tolerogen and induced immunological tolerance towards several antigens.

Rational design of a nanoparticle platform for oral prophylactic immunotherapy to prevent immunogenicity of therapeutic proteins.

The safety and efficacy of several life-saving therapeutic proteins are compromised due to their immunogenicity. Once a sustained immune response against a protein-based therapy is established, clinical options that are safe and cost-effective become limited. Prevention of immunogenicity of therapeutic proteins prior to their initial use is critical as it is often difficult to reverse an established immune response.

Tolerogenic form of Factor VIII to prevent inhibitor development in the treatment of Hemophilia A.

Background: The development of antidrug antibodies, also termed inhibitors, against administered factor VIII (FVIII) is one of the major complications in the clinical management of hemophilia A. Once formed, these inhibitory antibodies abrogate the activity of FVIII, resulting in loss of hemostatic efficacy and patients are subjected to increased risk of bleeding tendencies. Current treatment options after inhibitor development are expensive and ineffective in some cases.

Mechanics and Morphological Compensation Strategy for Trimmed Soft Whisker Sensor.

Recent studies have been inspired by natural whiskers for a proposal of tactile sensing system to augment the sensory ability of autonomous robots. In this study, we propose a novel artificial soft whisker sensor that is not only flexible but also adapts and compensates for being trimmed or broken during operation. In this morphological compensation designed from an analytical model of the whisker, our sensing device actively adjusts its morphology to regain sensitivity close to that of its original form (before being broken).