ADA References

INTRODUCTION: ABvac40 is an investigational active immunotherapy (vaccine) targeting Abeta40. This study assessed the safety and immunogenicity of ABvac40 in patients with amnestic mild cognitive impairment or very mild Alzheimer's disease. METHODS: AB1601 was a multicenter, randomized, double-blind, placebo-controlled phase 2 study. Patients (n = 124) received five monthly injections plus a 10-month booster of [...]

Bispecific antibodies (BsAbs) have emerged as a promising class of therapeutics to treat complex diseases, offering advantages in dual targeting simultaneously compared to monospecific antibodies. However, BsAbs often require advanced engineering, and the novel formats present challenges for the development of clinical anti-drug antibody (ADA) assays. Immunogenicity evaluation is a required study endpoint during the [...]

PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-gamma (IFN-gamma)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even [...]

CAR-T-cells can drive MHC class-I-mediated CD8 + cytotoxic T-cell response towards CAR constructs in addition to an antibody response. Immune response may also develop towards residuals present in the CAR-T cell product such as AAV, CRISPR/CAS9, and expamers. Health authorities recommend developing assays to assess both humoral and cellular immunogenicity towards the CAR-T protein. For [...]

Otodectes cynotis (ear mite), the primary etiological agent of feline otitis externa, represents a significant veterinary concern due to its high prevalence and treatment challenges. Glutathione S-transferase (GST), a detoxifying and immunogenic enzyme in various parasites, is a potential molecular target for vaccine development. In this study, we cloned and heterologously expressed the GST gene [...]

Comparative immunogenicity is a key regulatory requirement for biosimilars. In a streamlined biosimilar development process, absent a comparative clinical efficacy study, the analytical data and clinical pharmacokinetics (PK) study need to provide sufficient evidence for a conclusion of comparable immunogenicity. In this case study, we have reviewed the role of analytical and clinical data in [...]

Therapeutic protein administration in both preclinical and clinical studies can result in the formation of anti-drug antibodies against the therapeutic protein. Anti-drug antibody formation may alter the pharmacokinetics of the therapeutic protein, reduce its plasma concentrations, increase exposure variability, and may lead to a loss of efficacy and adverse events. In an effort to quantitatively [...]

Polyethylene glycol (PEG) has been widely used in household products from skin care and cosmetics, to baby wipes and cleaners, as well as protein biotherapeutics. More recently, PEG has become a critical component of lipid nanoparticles (e.g., LNP or Accurin platforms) used to deliver small molecule and ribonucleic acid (RNA) therapeutics. A potential concern with [...]

Immunogenicity of a therapeutic protein product may elicit an unintended immune response, and is a critical aspect evaluated in oncology clinical trials. The development of anti-drug antibodies (ADAs) can impact the pharmacokinetics, pharmacodynamics, efficacy, and safety of these therapies. We review the background and nomenclature of immunogenicity assessment in oncology studies and emphasize the complexities [...]

Vaccines are among the greatest achievements of modern medicine, and have saved countless lives. Subunit vaccines are vaccines made from specific parts (subunits) of a pathogen. Compared other types of vaccines, such as inactivated and live-attenuated vaccines, they are generally safer and more suitable for individuals with weakened immune systems. However, their immunogenicity is typically [...]