Backpack-carrying macrophage immunotherapy for periodontitis.

Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy.

Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy.

Tumour-associated neutrophils can exert antitumour effects but can also assume a pro-tumoural phenotype in the immunosuppressive tumour microenvironment. Here we show that neutrophils can be polarized towards the antitumour phenotype by discoidal polymer micrometric 'patches' that adhere to the neutrophils' surfaces without being internalized. Intravenously administered micropatch-loaded neutrophils accumulated in the spleen and in tumour-draining lymph nodes, and activated splenic natural killer cells and T cells, increasing the accumulation of dendritic cells and natural killer cells.

Backpack-mediated anti-inflammatory macrophage cell therapy for the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is a debilitating disease with no current therapies outside of acute clinical management. While acute, controlled inflammation is important for debris clearance and regeneration after injury, chronic, rampant inflammation plays a significant adverse role in the pathophysiology of secondary brain injury. Immune cell therapies hold unique therapeutic potential for inflammation modulation, due to their active sensing and migration abilities.

Preclinical characterization of macrophage-adhering gadolinium micropatches for MRI contrast after traumatic brain injury in pigs.

The choroid plexus (ChP) of the brain plays a central role in orchestrating the recruitment of peripheral leukocytes into the central nervous system (CNS) through the blood-cerebrospinal fluid (BCSF) barrier in pathological conditions, thus offering a unique niche to diagnose CNS disorders. We explored whether magnetic resonance imaging of the ChP could be optimized for mild traumatic brain injury (mTBI). mTBI induces subtle, yet influential, changes in the brain and is currently severely underdiagnosed.

Polymer Micropatches as Natural Killer Cell Engagers for Tumor Therapy.

Natural killer (NK) cell therapies have emerged as a potential therapeutic approach to various cancers. Their efficacy, however, is limited by their low persistence and anergy. Current approaches to sustain NK cell persistence include genetic modification, activation via pretreatment, or coadministration of supporting cytokines or antibodies.

A backpack-based myeloid cell therapy for multiple sclerosis.

Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS.

Extracellular matrix degrading enzyme with stroma-targeting peptides enhance the penetration of liposomes into tumors.

Various anti-tumor nanomedicines have been developed based on the enhanced permeability and retention effect. However, the dense extracellular matrix (ECM) in tumors remains a major barrier for the delivery and accumulation of nanoparticles into tumors. While ECM-degrading enzymes, such as collagenase, hyaluronidase, and bromelain, have been used to facilitate the accumulation of nanoparticles, serious side effects arising from the current non-tumor-specific delivery methods limit their clinical applications.

Strategies to improve the EPR effect: A mechanistic perspective and clinical translation.

Many efforts have been made to achieve targeted delivery of anticancer drugs to enhance their efficacy and to reduce their adverse effects. These efforts include the development of nanomedicines as they can selectively penetrate through tumor blood vessels through the enhanced permeability and retention (EPR) effect. The EPR effect was first proposed by Maeda and co-workers in 1986, and since then various types of nanoparticles have been developed to take advantage of the phenomenon with regards to drug delivery.

Cell therapies in the clinic.

Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes.

Gemcitabine and doxorubicin in immunostimulatory monophosphoryl lipid A liposomes for treating breast cancer.

Cancer therapy is increasingly shifting toward targeting the tumor immune microenvironment and influencing populations of tumor infiltrating lymphocytes. Breast cancer presents a unique challenge as tumors of the triple-negative breast cancer subtype employ a multitude of immunosilencing mechanisms that promote immune evasion and rapid growth. Treatment of breast cancer with chemotherapeutics has been shown to induce underlying immunostimulatory responses that can be further amplified with the addition of immune-modulating agents.

Engineering of Living Cells with Polyphenol-Functionalized Biologically Active Nanocomplexes.

Approaches to safely and effectively augment cellular functions without compromising the inherent biological properties of the cells, especially through the integration of biologically labile domains, remain of great interest. Here, a versatile strategy to assemble biologically active nanocomplexes, including proteins, DNA, mRNA, and even viral carriers, on cellular surfaces to generate a cell-based hybrid system referred to as "Cellnex" is established. This strategy can be used to engineer a wide range of cell types used in adoptive cell transfers, including erythrocytes, macrophages, NK cells, T cells, etc.

Cellular backpacks for macrophage immunotherapy.

Adoptive cell transfers have emerged as a disruptive approach to treat disease in a manner that is more specific than using small-molecule drugs; however, unlike traditional drugs, cells are living entities that can alter their function in response to environmental cues. In the present study, we report an engineered particle referred to as a "backpack" that can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. Backpacks evade phagocytosis for several days and release cytokines to continuously guide the polarization of macrophages toward antitumor phenotypes.

Materials for Immunotherapy.

Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation.