Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of nonresponders also call for development of antigen‐independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, the impressive trafficking ability of adoptively transferred monocytes is leveraged into the immunosuppressive 4T1 tumor to develop an antitumor therapy. To control monocyte differentiation in the tumor microenvironment, surface‐adherent “backpacks” stably modified with interferon gamma (IFNγ) are developed to stimulate macrophage plasticity into a pro‐inflammatory, antitumor phenotype, a strategy as referred to as Ornate Polymer backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduces tumor burden in a mouse 4T1 model and significantly increases survival. Cytokine and immune cell profiling reveal that OPTIMs remodeled the tumor microenvironment into a pro‐inflammatory state.
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Abstract -
Adebowale, Kolade ; Liao, Rick ; Suja, Vineeth Chandran ; Kapate, Neha ; Lu, Andrew ; Gao, Yongsheng ; Mitragotri, Samir ( , Advanced Materials)
Abstract Cell therapies are emerging as a promising new therapeutic modality in medicine, generating effective treatments for previously incurable diseases. Clinical success of cell therapies has energized the field of cellular engineering, spurring further exploration of novel approaches to improve their therapeutic performance. Engineering of cell surfaces using natural and synthetic materials has emerged as a valuable tool in this endeavor. This review summarizes recent advances in the development of technologies for decorating cell surfaces with various materials including nanoparticles, microparticles, and polymeric coatings, focusing on the ways in which surface decorations enhance carrier cells and therapeutic effects. Key benefits of surface‐modified cells include protecting the carrier cell, reducing particle clearance, enhancing cell trafficking, masking cell‐surface antigens, modulating inflammatory phenotype of carrier cells, and delivering therapeutic agents to target tissues. While most of these technologies are still in the proof‐of‐concept stage, the promising therapeutic efficacy of these constructs from in vitro and in vivo preclinical studies has laid a strong foundation for eventual clinical translation. Cell surface engineering with materials can imbue a diverse range of advantages for cell therapy, creating opportunities for innovative functionalities, for improved therapeutic efficacy, and transforming the fundamental and translational landscape of cell therapies.
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Wang, Lily Li‐Wen ; Janes, Morgan E. ; Kumbhojkar, Ninad ; Kapate, Neha ; Clegg, John R. ; Prakash, Supriya ; Heavey, Mairead K. ; Zhao, Zongmin ; Anselmo, Aaron C. ; Mitragotri, Samir ( , Bioengineering & Translational Medicine)
Abstract 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. As such, cell therapies are currently one of the most investigated therapeutic modalities in both preclinical and clinical settings, with many products having been approved and many more under active clinical investigation. Here, we highlight the diversity and key advantages of cell therapies and discuss their current clinical advances. In particular, we review 28 globally approved cell therapy products and their clinical use. We also analyze >1700 current active clinical trials of cell therapies, with an emphasis on discussing their therapeutic applications. Finally, we critically discuss the major biological, manufacturing, and regulatory challenges associated with the clinical translation of cell therapies.