Engineering Cells for Cancer Therapy.

in Accounts of chemical research by Peixin Liu, Quanyin Hu

TLDR

  • Engineered cells are living cells that have been modified or enhanced using biological or chemical engineering techniques. They can be used for therapeutics or drug delivery purposes. The authors propose the concept of engineered cells to avoid the laborious process of isolating, modifying, and expanding engineered cells. They present three successful examples of engineered cells in cancer therapy: targeting tumor-associated macrophages for gene editing, suppressing postoperative tumor recurrence using antiprogrammed death 1 (PD-1) antibodies on platelets, and inducing cancer cell death through pyroptosis initiation and immunotherapy strategies using engineered bacteria. The authors identify several limitations of the study that need to be addressed in future research, including the need for further optimization of engineered cells for clinical translation purposes. They suggest several possible future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches. These include the development of more efficient and cost-effective methods for large-scale production of engineered cells, the exploration of new functionalities and applications of engineered cells, and the integration of engineered cells with other advanced technologies such as nanotechnology and bioprinting.

Abstract

ConspectusCells, particularly living cells, serve as natural carriers of bioactive substances. Their inherent low immunogenicity and multifunctionality have garnered significant attention in the realm of disease treatment applications, specifically within the domains of cancer immunotherapy and regenerative tissue repair. Nevertheless, several prominent challenges impede their swift translation into clinical applications, including obstacles related to large-scale production feasibility and high utilization costs. To address these issues comprehensively, researchers have proposed the notion of bionic cells that are synthetically generated through chemical or biosynthetic means to emulate cellular functions and behaviors. However, artificial cell strategies encounter difficulties in fully replicating the intricate functionalities exhibited by living cells while also grappling with the complexities associated with design implementation for clinical translation purposes. The convergence of disciplines has facilitated the reform of living cells through a range of approaches, including chemical-, biological-, genetic-, and materials-based methods. These techniques can be employed to impart specific functions to cells or enhance the efficacy of therapy. For example, cells are engineered through gene transduction, surface modifications, endocytosis of drugs as delivery systems, and membrane fusion. The concept of engineered cells presents a promising avenue for enhancing control over living cells, thereby enhancing therapeutic efficacy while concurrently mitigating toxic side effects and ultimately facilitating the realization of precision medicine.In this Account, we present a comprehensive overview of our recent research advancements in the field of engineered cells. Our work involves the application of biological or chemical engineering techniques to manipulate endogenous cells for therapeutics or drug delivery purposes. For instance, to avoid the laborious process of isolating, modifying, and expanding engineered cells, we proposed the concept ofengineered cells. By applying a hydrogel loaded with nanoparticles carrying edited chimeric antigen receptor (CAR) plasmids within the postoperative cavity of glioma, we successfully targeted tumor-associated macrophages for gene editing, leading to effective tumor recurrence inhibition. Furthermore, leveraging platelet's ability to release microparticles upon activation at injury sites, we modified antiprogrammed death 1 (PD-1) antibodies on their surface to suppress postoperative tumor recurrence and provide immunotherapy for inoperable tumors. Similarly, by exploiting bacteria's active tropism toward sites of inflammation and hypoxia, we delivered protein drugs by engineered bacteria to induce cancer cell death through pyroptosis initiation and immunotherapy strategies. In the final section, we summarize our aforementioned research progress while providing an outlook on cancer therapy and the hurdles for clinical translation with potential solutions or future directions based on the concept of engineered cells.

Overview

  • The study focuses on the manipulation of endogenous cells for therapeutics or drug delivery purposes using biological or chemical engineering techniques. The authors propose the concept of engineered cells to avoid the laborious process of isolating, modifying, and expanding engineered cells. They present three examples of successful application of engineered cells in cancer therapy: targeting tumor-associated macrophages for gene editing, suppressing postoperative tumor recurrence using antiprogrammed death 1 (PD-1) antibodies on platelets, and inducing cancer cell death through pyroptosis initiation and immunotherapy strategies using engineered bacteria. The study aims to enhance control over living cells, thereby enhancing therapeutic efficacy while concurrently mitigating toxic side effects and ultimately facilitating the realization of precision medicine.

Comparative Analysis & Findings

  • The study presents three successful examples of engineered cells in cancer therapy: targeting tumor-associated macrophages for gene editing, suppressing postoperative tumor recurrence using antiprogrammed death 1 (PD-1) antibodies on platelets, and inducing cancer cell death through pyroptosis initiation and immunotherapy strategies using engineered bacteria. The authors compare the outcomes observed under different experimental conditions or interventions detailed in the study. They identify significant differences or similarities in the results between these conditions. The key findings of the study include successful targeting of tumor-associated macrophages for gene editing, suppression of postoperative tumor recurrence using antiprogrammed death 1 (PD-1) antibodies on platelets, and induction of cancer cell death through pyroptosis initiation and immunotherapy strategies using engineered bacteria. These findings suggest that engineered cells can be a promising avenue for enhancing control over living cells, thereby enhancing therapeutic efficacy while concurrently mitigating toxic side effects and ultimately facilitating the realization of precision medicine.

Implications and Future Directions

  • The study's findings suggest that engineered cells can be a promising avenue for enhancing control over living cells, thereby enhancing therapeutic efficacy while concurrently mitigating toxic side effects and ultimately facilitating the realization of precision medicine. The authors identify several limitations of the study that need to be addressed in future research, including the need for further optimization of engineered cells for clinical translation purposes. They suggest several possible future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches. These include the development of more efficient and cost-effective methods for large-scale production of engineered cells, the exploration of new functionalities and applications of engineered cells, and the integration of engineered cells with other advanced technologies such as nanotechnology and bioprinting.
Read Full Article