Harnessing the Potential of Biomimicry for Immune Therapeutics

Biomimicry is the process of imitating nature's solutions to solve human problems. In the field of immune therapeutics, biomimicry can offer novel and effective strategies to modulate the immune system and treat various diseases, such as cancer, autoimmune disorders, and allergies.

One of the main challenges of immune therapeutics is delivering drugs or vaccines to the desired target cells or tissues while avoiding unwanted side effects or immune responses. Nanoparticle-based drug delivery systems have been implemented for years. This platform has been widely developed due to its stability, improved drug solubility, high drug payload, and ability to allow various routes of administration, especially for parenteral applications. Traditionally, nanoparticles are designed to passively target tumor sites by taking advantage of the persistent enhanced permeability and retention (EPR) effect in the tumor environment. In this condition, an elevated increase in vascular endothelial growth factor, nitric oxide, peroxynitrite, and bradykinin increases the inter-endothelial cell gaps, resulting in increased vascular permeability, which then enables the nanoparticles to permeate more easily into the tumor site. Furthermore, the lack of lymphatic drainage in tumors ensures that the nanoparticles are retained, resulting in increased accumulation over time. Generally, conventional nanoparticle drug carriers are liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymers, dendrimers, micelles, and magnetic and inorganic nanoparticles. Among them, those made with biodegradable materials, induce lower toxicity and are retained longer in the circulatory system.

Unfortunately, there are some obstacles due to tumor heterogeneity and the natural defense system of mammalian organisms. It was reported that the intensity of the EPR effect is largely influenced by the heterogeneity of the EPR effect within the tumors, tumor staging, and different tumor types. Different tumor types have different vasculatures, which can influence the tumor's physiological environment, such as the vascular structure, blood flow rate, and vascular permeability. In addition, the physicochemical properties of nanoparticles such as their size, shape, and surface charges also contribute to the variations in the EPR effect and drug accumulation. This makes it difficult to predict the success of a nanoparticle-based drug delivery system that solely relies on the EPR effect. Additionally, the reticuloendothelial system (RES) is another main obstacle that clears out the nanoparticles from the body once they are recognized as “foreign materials”, leading to a poor therapeutic outcome. Besides the RES system, the off-targeting effect of nanoparticles is also one of the major challenges where nanoparticle accumulation in organs such as the kidneys, heart, lungs, or bone marrow may elicit unwanted toxicity, induce undesired immune responses and lower the overall accumulation in the tumor.

Nanotechnology can help overcome this challenge by creating nanoscale carriers that can mimic the biological characteristics of cells that naturally infiltrate tumors or inflamed tissues. These carriers are called cell membrane-based biomimetic nanoparticles (CBNPs) and they are made by coating synthetic nanoparticles with the membrane of donor cells, such as leukocytes, mesenchymal cells, erythrocytes, neutrophils, NK, macrophages, platelets, etc. CBNPs can inherit the surface proteins, receptors, and antigens of the donor cells, which can enhance their circulation, targeting, and immune modulation abilities.

For example, CBNPs derived from red blood cells can evade phagocytosis by macrophages and prolong their circulation time in the blood. CBNPs derived from platelets can bind to endothelial cells and facilitate their extravasation into tumor tissues. CBNPs derived from macrophages can activate antigen-presenting cells and induce anti-tumour immunity. CBNPs derived from regulatory T cells can suppress inflammatory cytokines and prevent autoimmune reactions. CBNPs derived from mast cells can deliver allergens and induce tolerance in allergic patients. Given the tropism of neutrophils migrating to inflammatory tissue and engagement in multifarious inflammatory responses, activated neutrophils are deemed as targeted drug delivery vectors for the therapy of inflammation-related diseases, including malignant tumors, autoimmune conditions, and cardiovascular disease.

Challenges:

1. Instability of BNPs. The size, shape, components, and physical-chemical characteristics of vectors vary from modifications and different sources, which can significantly affect their performance
2. Complex preparation methods are difficult to achieve large-scale production, which limits the clinical translation of BNPs. A more intelligent and effective manner for extraction and coating is urgently required to obtain biocompatible vectors with high purity, plasticity, and reproducibility
3. The biological safety and bioactive effect of BNPs remain unclear in human beings

The potential applications of CBNPs for immune therapeutics are vast and promising. However, there are still some challenges and limitations that need to be addressed, such as the scalability, stability, safety, and regulation of these platforms. Therefore, more research and development are needed to optimize the design, fabrication, and evaluation of CBNPs for clinical use.

Here are the top 5 companies working on biomimicry for immune therapeutics:

• Elicio Therapeutics: This company is developing a platform called Amphiphile (AMP), which consists of synthetic nanoparticles coated with cell membrane-derived lipids and antigens. AMPs can activate lymph nodes and elicit potent immune responses against cancer or infectious diseases. The company is based in Cambridge, UK. It has raised +200 MM USD between equity and debt and is currently developing a phase 1 for its main asset, ELI-002 2P an investigational therapeutic cancer vaccine.

• Cytovia Therapeutics: This company is developing a platform called Natural Killer Cell Engager (NKCE), which consists of synthetic nanoparticles coated with natural killer cell membrane-derived proteins and antibodies. NKCEs can target and kill tumor cells or virus-infected cells. The company is based in Florida, US, and raised +45MM USD from a new joint venture with China investors.

• Cour Pharmaceutical Development Company: This company is developing a platform called Tolerizing Immune Modifying nanoParticles (TIMP), which consists of synthetic nanoparticles coated with antigen-presenting cell membrane-derived proteins and antigens. TIMPs can induce immune tolerance and prevent or reverse autoimmune diseases. The company is based in Skokie, Illinois, United States, and raised + 30 MM USD from Alpha Wave Ventures

• Selecta Biosciences: This company is developing a platform called ImmTOR, which consists of synthetic nanoparticles coated with rapamycin, a drug that modulates the immune system. ImmTOR can enhance the efficacy and safety of gene therapies or biologics by reducing unwanted immune responses. The company is public with its HQ in Watertown, Massachusetts, United States, and raised + 300 MM USD in total after its IPO.

• Evox Therapeutics: This company is developing a platform called exosome, which consists of natural nanoparticles secreted by cells that carry various biomolecules. Exosomes can deliver drugs or vaccines to specific cells or tissues and modulate their function. The company is based in Oxford, Oxfordshire, United Kingdom, and raised + 160 MM USD in total after a C series. Last week Evox has been granted US Patent US11,640,272. The claims of this patent cover a method of purifying engineered exosomes via a downstream process utilizing ultrafiltration and size-based separation steps. Importantly this patent protects a process that is widely used in the field of exosome therapeutics. Taken together with four other manufacturing patents issued to Evox during 2022 this builds upon Evox’s manufacturing patent protection which now covers key purification and loading methods in key jurisdictions.

Biomimicry is a promising strategy for designing novel immune therapeutics that can overcome the limitations of conventional drugs. By mimicking natural immune cells, biomimetic nanoparticles can achieve higher specificity, efficacy, and safety in targeting various immune-related diseases. Biomimicry is also a source of inspiration for discovering new mechanisms and pathways of immune regulation that can be exploited for therapeutic purposes.

What do you think about the potential of biomimicry for immune therapeutics? Have you heard of any other exciting developments in this field? Let me know in the comments below!

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