How To Bridge Non-Clinical and Clinical Immunogenicity?

Assessing immunogenicity is a cornerstone of modern drug development, especially for biologics and vaccines. Understanding how the immune system interacts with therapeutic agents is essential to ensure safety and efficacy. However, traditional methods of evaluating immunogenicity often fall short of accurately predicting human immune responses, creating a critical need for innovative tools that better mimic human biology. This article explores why immunogenicity testing matters, the limitations of current approaches, and how ex vivo human skin models are reshaping this field.

Why is assessing drug immunogenicity key for biopharmaceutical companies?

The immune system defends the body by identifying and neutralizing invaders like viruses and bacteria. However, it can also react to therapeutic agents, potentially reducing their efficacy and causing adverse reactions.

Immunogenicity—the immune response to drugs or vaccines—is critical in determining their safety and efficacy. For vaccines, a strong immune response is essential for protection, while in drugs, unwanted immune reactions may neutralize their effects or cause harm. Regulatory agencies like the FDA and EMA require immunogenicity assessment to ensure therapeutic benefits outweigh the risks.

Immunogenicity studies also support personalized medicine by predicting patient-specific responses, enabling tailored treatments. Furthermore, these studies guide drug design by helping scientists modify biologics to reduce immune reactions while preserving efficacy, a key factor in developing biosimilars and next-generation therapies. Understanding and managing immunogenicity is therefore pivotal in developing safe and effective biopharmaceuticals.

What are the limits of immunogenicity testing today?

Immunogenicity testing is a crucial component of drug development, particularly for biologic therapies, but current methods face significant limitations. In vitro assays and animal models are often not able to predict human immune responses due to the complexity and individuality of the human immune system. Animal models may fail to replicate key human immune mechanisms, and in vitro tests cannot fully encompass the intricacies of in vivo responses.

Consequently, preclinical findings may not reliably translate to human clinical outcomes. Additionally, immunogenicity testing is time-consuming and resource-intensive, especially in early development stages. These constraints can limit the exploration of immunogenic epitopes, dosing regimens, and administration routes, as well as hinder assessments of long-term immunogenicity risks. Addressing these challenges requires the development of more predictive and efficient preclinical tools to improve immunogenicity assessments, ensuring safer and more effective biologic therapies for patients.

Human skin: A relevant tool to assess drug immunogenicity

Human skin is a sophisticated immune organ, completely equipped to assess immunogenicity. Its cutaneous immune system hosts a diverse network of immune and structural cells, including antigen-presenting cells (APCs), T cells, B cells, mast cells, and granulocytes, all of which play pivotal roles in immune defense and tissue homeostasis. With the growing trend towards skin-based drug delivery methods—such as microneedles and transdermal patches—human skin offers distinct advantages. Skin delivery bypasses first-pass metabolism, enabling enhanced drug effectiveness, and supports sustained, controlled release. Intradermal vaccine administration can elicit robust immune responses at lower doses compared to traditional routes, while being less invasive and painful.

Genoskin leverages this potential with ex vivo human skin models, offering a highly predictive platform to evaluate drug and vaccine immunogenicity. The HypoSkin® model preserves the skin’s structural integrity and immune competence for up to seven days, enabling multiparameter immune profiling. Genoskin’s platforms, such as ImmunoSafe ISR Platform® for immunotoxicity assessment and VaxSkin® for vaccine immune response profiling1, provide unparalleled insights into human immune mechanisms. These innovative tools are advancing drug development, offering safer, more efficient paths to therapeutic advancement by bridging non-clinical and clinical immunogenicity evaluations.

Advancing immunogenicity testing is pivotal for creating safer, more effective therapies. By addressing current limitations and leveraging innovative platforms like Genoskin’s ex vivo human skin models, biopharmaceutical companies can achieve a deeper understanding of immune responses. These solutions are driving the future of biopharmaceutical innovation by bridging the gap between non-clinical and clinical testing.

To learn more about Genoskin’s immunogenicity assessment solutions, visit their website or contact contact@genoskin.com.

References

1. Scholaert M, Peries M, Braun E, et al. Multimodal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine. Allergy. 2024; 00: 1-19. doi:10.1111/all.16273