Does stability of mabs has an influence on the tissue distribution of mabs?
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The stability of monoclonal antibodies (mAbs) can have an influence on their tissue distribution . Factors such as the folding and conformation of the immunoglobulin (Ig) domain, which is the basis for the structure of mAbs, can impact their stability . Unfolding of mAb fragments can lead to loss of specificity and non-native interactions, resulting in protein aggregation . Aggregated antibody fragments can display altered pharmacokinetic properties, including tissue distribution, and increased immunogenicity and toxicity . Additionally, the physicochemical properties of mAbs, such as charge and hydrophobicity, can affect their subcutaneous absorption and bioavailability, which can in turn influence tissue distribution . Therefore, understanding and optimizing the stability of mAbs is important for their tissue distribution and overall therapeutic efficacy .
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| Papers (5) | Insight |
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| The provided paper does not discuss the influence of monoclonal antibody (MAb) stability on tissue distribution. The paper focuses on the effects of ionic strength and sugars on the aggregation propensity of MAbs. | |
| The provided paper does not mention anything about the influence of mAb stability on tissue distribution. | |
| The paper does not specifically mention the influence of mAb stability on tissue distribution. The paper focuses on the influence of physiochemical properties on subcutaneous absorption and bioavailability of mAbs. | |
| The paper does not directly address the influence of mAb stability on tissue distribution. The paper focuses on strategies to stabilize antibody fragments and minimize aggregation. | |
37 Citations | The provided paper does not directly address the stability of mAbs and its influence on tissue distribution. |
Related Questions
Lower Tm of antibody means lower stability ??4 answersLowering the melting temperature (Tm) of an antibody typically indicates lower stability. Antibody stability is crucial for its expression, activity, specificity, and storage. Strategies such as computer-aided molecule design have been employed to optimize and enhance antibody stability. In the context of antibody-antibody coformulations, it has been observed that the stability of one antibody component can influence the stability of another component in the mixture. Furthermore, interactions between antibodies in a coformulation can lead to alterations in their stability and degradation profiles. Therefore, a lower Tm of an antibody generally signifies reduced stability, which can impact its overall performance and efficacy in various applications.
What is the difference in tissue distribution of mAbs between healthy and sick patients?5 answersThe tissue distribution of monoclonal antibodies (mAbs) in healthy and sick patients can vary based on factors like target antigen density, turnover rate, and target antigen expression profile. In healthy individuals, mAbs tend to accumulate in tissues like the liver, spleen, kidney, and intestines, with lower concentrations in bone marrow, lung, muscle, fat, and the brain. Factors influencing mAb distribution include molecular weight, blood flow, and tissue heterogeneity. Additionally, mAbs have slow tissue distribution due to their large molecular size, leading to low volumes of distribution. Understanding these differences is crucial for effective therapeutic application of mAbs in both healthy and sick patients, as variations in tissue distribution can impact the pharmacological responses observed in different clinical settings.
Which models exist to predict tissue distribution mAbs?5 answersVarious models have been developed to predict tissue distribution of monoclonal antibodies (mAbs). These include physiologically-based pharmacokinetic (PBPK) models integrated with target-mediated drug disposition (TMDD) models, which consider tissue dynamics and target interactions. Additionally, whole-body physiologically-based models have been created to predict mAb pharmacokinetics following subcutaneous administration, incorporating parameters for mAb transport, lymphatic uptake, and pre-systemic clearance. Furthermore, the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been explored to improve physiologically based pharmacokinetic model predictions of mAb distribution in solid tumors, enhancing individualized dosing strategies and patient selection for anti-cancer mAb treatment. These models offer valuable insights into mAb tissue distribution, aiding in the optimization of dosing regimens and therapeutic outcomes.
How to reduce Low Molecular Weight Impurities in cell culture process for mAbs?5 answersTo reduce Low Molecular Weight (LMW) impurities in the cell culture process for monoclonal antibodies (mAbs), several strategies can be implemented. Firstly, depth filtration-based harvesting can be utilized to control product-related impurities, including LMWs, through interactions with depth filters based on hydrophobic interactions. Additionally, downstream processes like Protein A chromatography and cation exchange chromatography have shown excellent clearances for LMW impurities, with overall clearances of up to 5,000-fold in a typical mAb downstream process. Furthermore, optimizing the pH of wash buffers in Protein A chromatography and incorporating additives to disrupt protein-protein interactions can lead to a more pronounced reduction in impurity levels, including LMWs, during the purification process. These approaches collectively contribute to effectively reducing LMW impurities in the cell culture process for mAbs.
What is the role of molecular charge in the tissue distribution and pharmacokinetics of monoclonal antibodies?5 answersMolecular charge plays a significant role in the tissue distribution and pharmacokinetics of monoclonal antibodies (mAbs). Lowering the isoelectric point (pI) through charge engineering can improve mAb exposure and half-life by reducing clearance mediated through non-specific interactions. Balancing the net positive charge on mAbs can lead to improved pharmacokinetics, with lower positive charge resulting in a longer half-life and reduced tissue catabolism. The charge of mAbs can also influence non-specific binding, cellular degradation, clearance, distribution, and metabolism. Positive charge patches on mAbs can increase nonspecific binding and pinocytosis rate in various tissues, while negative charge patches can have a differential effect on non-specific binding. Surface charges of mAbs are important parameters to consider in the selection and screening of humanized candidates for clinical development, as they contribute to mAb disposition in vivo. Overall, molecular charge is a crucial factor in determining the tissue distribution and pharmacokinetics of mAbs.
What are the most effective elution buffer additives for increasing mAb stability?5 answersThe most effective elution buffer additives for increasing monoclonal antibody (mAb) stability include hexylene glycol and arginine. These additives have been shown to facilitate protein elution from resins used in hydrophobic interaction chromatography (HIC) and improve protein recovery while reducing soluble product aggregate and host cell protein. Additionally, choline-based buffered ionic liquids (BILs) have been found to enhance the stability of epidermal growth factor receptor monoclonal antibody (EGFR mAb). An equimolar mixture of l-Arg and l-Glu (Arg·Glu) has also been shown to increase the colloidal and conformational stability of monoclonal antibodies, especially at neutral pH. These findings suggest that hexylene glycol, arginine, BILs, and Arg·Glu can be effective additives for improving mAb stability in elution buffers.