Self-Assembly as a Molecular Strategy to Improve Immunotherapy

Abstract

Conspectus Immunotherapies harness an individual’s immune system to battle diseases such as cancer and autoimmunity. During cancer, the immune system often fails to detect and destroy cancerous cells, whereas during autoimmune disease, the immune system mistakenly attacks self-tissue. Immunotherapies can help guide more effective responses in these settings, as evidenced by recent advances with monoclonal antibodies and adoptive cell therapies. However, despite the transformative gains of immunotherapies for patients, many therapies are not curative, work only for a small subset of patients, and lack specificity in distinguishing between healthy and diseased cells, which can cause severe side effects. From this perspective, self-assembled biomaterials are promising technologies that could help address some of the limitations facing immunotherapies. For example, self-assembly allows precision control over the combination and relative concentration of immune cues and directed cargo display densities. These capabilities support selectivity and potency that could decrease off-target effects and enable modular or personalized immunotherapies. The underlying forces driving self-assembly of most systems in aqueous solution result from hydrophobic interactions or charge polarity. In this Account, we highlight how these forces are being used to self-assemble immunotherapies for cancer and autoimmune disease. Hydrophobic interactions can create a range of intricate structures, including peptide nanofibers, nanogels, micelle-like particles, and in vivo assemblies with protein carriers. Certain nanofibers with hydrophobic domains uniquely benefit from the ability to elicit immune responses without additional stimulatory signals. This feature can reduce nonspecific inflammation but may also limit the nanofiber’s application because of their inherent stimulatory properties. Micelle-like particles have been developed with the ability to incorporate a range of tumor-specific antigens for immunotherapies in mouse models of cancer. Key observations have revealed that both the total dose of antigen and display density of antigen per particle can impact immune response and efficacy of immunotherapies. These developments are promising benchmarks that could reveal design principles for engineering more specific and personalized immunotherapies. There has also been extensive work to develop platforms using electrostatic interactions to drive assembly of oppositely charged immune signals. These strategies benefit from the ability to tune biophysical interactions between components by altering the ratio of cationic to anionic charge during formulation, or the density of charge. Using a layer-by-layer assembly method, our lab developed hollow capsules composed entirely of immune signals for therapies in cancer and autoimmune disease models. This platform allowed for 100% of the immunotherapy to be composed of immune signals and completely prevents the onset of disease in a mouse model of multiple sclerosis. Layer-by-layer assembly has als...

Enhanced Sunscreen Effects via Layer-By-Layer Self-Assembly of Chitosan/Sodium Alginate/Calcium Chloride/EHA

“…The way of layer-by-layer self-assembly (LBL) was a new strategy to prepare the nanocapsules with nano-size and good dispersibility [ 11 ]. Due to its mechanism that was deposited oppositely charged polyelectrolytes with the interaction of electrostatic interaction, thus the morphology [ 12 ], size and other properties of the nanocapsules could be controlled by adjusted the number of assembly layers [ 13 ]. Unlike other methods, the nanocapsules prepared by LBL technology could be adjusted according to demands, such as controlled the diffusion rate by adjusted the thickness of wall, changed the shape by adjusted the pH and ionic strength of solutions, prepared multi component composite shell by used many kinds of materials [ 14 ].…”

Biomaterial-enabled induction of pancreatic-specific regulatory T cells through distinct signal transduction pathways

“…Antigen-specific, tolerizing therapies offer the potential to revolutionize the way autoimmune diseases are treated. Due to the important role of location and timing in the immune response, biomaterials have emerged as a potent tool to control these parameters [24,26,27]. In particular, the importance of timing and location for the immune system has increased exploration of biomaterials as ways to manipulate vaccine responses [46,47].…”

“…Biomaterials offer distinct advantages for the delivery of immune cargo, allowing for cargo protection, codelivery, and targeting specific tissues and cell populations. These technologies -including self-assembled constructs and microparticles/nanoparticles (MP/NPs) -have recently been intensely studied for both proimmune and tolerance contexts [24][25][26][27][28][29][30][31]. For example, delivery of cargo in MP/NPs can increase targeting of particular tissues and cell populations such as lymph nodes 32.…”

Self-assembling peptides-based nano-cargos for targeted chemotherapy and immunotherapy of tumors: recent developments, challenges, and future perspectives

“…Cancer cells frequently suppress the immune system in the tumor environment, preventing it from performing effective antitumor responses (Froimchuk et al., 2020 ). To address some of the shortcomings of conventional immunotherapy, SAPs have emerged as a promising technology that offers numerous advantages including efficient loading of cargo, multivalent antigen presence, and enhanced cellular uptake (Cai et al., 2020 ; Froimchuk et al., 2020 ). Tirrell et al.…”