Immunoengineering: A New Frontier for Autoimmune Kidney Disease Treatment

Autoimmune kidney diseases continue to pose significant challenges in achieving long-term remission for many patients. Despite advancements in the field, the use of non-targeted immunosuppressive agents remains a primary cause of morbidity due to their adverse effects.

However, recent studies involving sophisticated molecular technologies promise a new era of tailored, disease-modifying treatments. One such promising avenue, as a new manuscript published by Oxford University Press on behalf of the ERA shows, is immunoengineering, which aims to utilize chemically engineered biomaterials for precision medicine.

At a Glance

Unmet Needs: Persistent issues with current immunosuppressive treatments
Emerging Solutions: Molecular technologies like proteomics, transcriptomics, and single-cell genomics
Focus Area: Immunoengineering for precise and targeted therapy

The Promise of Immunoengineering

Tailored Nanoparticles

Nanoparticles, ranging from 5 nm to 200 nm, can be designed for specific applications by modifying their composition, size, and geometry. These particles can be coated or conjugated with ligands to enable tailored applications. For instance, nanoparticles can be engineered to activate immune cells and be recognized by antigen-presenting cells. Additionally, albumin-bound nanoparticles can facilitate the transport of therapeutic agents to lymph nodes, enhancing their efficacy.

Microparticles as Biodegradable Depots

Microparticles, typically tens of microns in size, can encapsulate immunomodulatory compounds and serve as biodegradable tissue-resident depots. These particles can resist phagocytosis and remain in desired locations for extended periods. This makes them an appealing option for delivering agents to target tissues, a concept already realized in oncology. However, delivering these particles into the kidneys remains a significant challenge due to the complex structure of the organ.

Macroscale Materials

Macroscale materials, which can be biological or synthetic, offer another promising option. These materials can be used to create microenvironments that mimic tissues, ranging from organoids to organs-on-chips. Such environments can help test new hypotheses and facilitate the development of new therapeutic approaches.

Applications in Autoimmune Kidney Diseases

Immunoregulation and Tolerization

Nanoparticles distributed in the lymphatic system, particularly with the help of albumin, can deliver agents that have limited efficacy when administered systemically. For example, albumin-bound Interleukin-10 (IL-10) has shown anti-inflammatory effects within the lymphatic system. Similar concepts can be applied to other anti-inflammatory cytokines like IL-4, which plays a role in diseases such as systemic lupus erythematosus and lupus nephritis (LN).

Gut-Targeted Immunoengineering

Gut-targeted nanoparticles can be designed to induce immunoregulation through epigenetic modifications. For example, polymeric micelles that deliver butyrate can modulate gut microbiota, potentially benefiting patients with IgA nephropathy (IgAN). Recent studies have shown that bacteria like Akkermansia muciniphila can deglycosylate human IgA1, making it recognizable by autoantibodies. Nanoparticles that suppress the activity of such bacteria could be useful in treating IgAN.

CAR T-Cell Therapies

Chimeric antigen receptor (CAR) T-cell therapies are being explored as a potential treatment for refractory autoimmune diseases, including LN. Macroscale extracellular matrix scaffolds can be engineered to improve the quality and efficacy of CAR T-cells by tuning their viscoelastic mechanical properties.

Challenges and Future Directions

While the potential of immunoengineering is immense, several challenges remain. These include the need for thorough evaluation in preclinical models, the development of novel compounds, and the design of well-structured clinical trials. Additionally, practical issues such as delivering these engineered compounds into the kidneys and managing the cost-effectiveness of the process need to be addressed.

In conclusion, immunoengineering offers a promising future for the treatment of autoimmune kidney diseases. As the authors aptly put it:

With continued research and development, immunoengineering could revolutionize the management of autoimmune kidney diseases, offering more precise and effective treatment options for patients.

Immunoengineering: Transforming Autoimmune Kidney Disease Treatment