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Published on: April 17, 2021
Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical
Zheng Sun1,2, Jun Ge1, Hui Fu3
1College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Abstract:
Conventional drug-delivery systems (DDSs) for oncology often face challenges such as insufficient tumor selectivity, rapid systemic clearance, limited penetration across stromal and immune barriers, and suboptimal biocompatibility. Live immune cell-based drug-delivery systems (LCDDSs) overcome these limitations by exploiting the innate tumor-homing capacity, high biocompatibility, and dynamic tumor microenvironment (TME) interactions intrinsic to leukocytes, facilitating precise targeting with minimal systemic toxicity. Furthermore, immune cells act as "mobile microprocessors", actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME. Nonetheless, the clinical translation of LCDDSs remains impeded by limited drug-loading capacities, premature payload degradation, potential impairment of immune-cell function, and insufficient persistence in immunosuppressive environments. To overcome these hurdles, immune cell reprogramming via genetic, metabolic, or epigenetic modifications emerges as a promising strategy. Such interventions improve cellular fitness, enhance tumor infiltration, augment payload transport efficiency, confer programmable release profiles, mitigate cellular exhaustion, and increase adaptability to the hostile TME. This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits, drug compatibility considerations, payload loading strategies, and design criteria essential for achieving clinical controllability, safety, and scalability. By integrating immune-cell engineering with cutting-edge drug delivery technologies, reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.
Insights
Reprogramming immune cells enhances live immune cell-based drug-delivery systems (LCDDSs) for precision oncology. Engineered LCDDSs overcome limitations for improved tumor targeting and therapeutic efficacy.
Area of Science:
- Biomedical Engineering
- Cancer Therapeutics
- Immunology
Background:
- Conventional drug-delivery systems (DDSs) for cancer face challenges like poor tumor selectivity and systemic toxicity.
- Live immune cell-based drug-delivery systems (LCDDSs) leverage leukocytes' tumor-homing and biocompatibility for targeted delivery.
- Current LCDDSs struggle with drug loading, payload stability, and persistence in immunosuppressive tumor microenvironments (TMEs).
Purpose of the Study:
- To review how immune cell reprogramming advances LCDDSs for precision oncology.
- To evaluate mechanistic benefits, drug compatibility, loading strategies, and design criteria for clinical translation.
- To highlight reprogrammed LCDDSs as a platform for next-generation cancer therapeutics.
Main Methods:
- Systematic evaluation of immune cell reprogramming strategies (genetic, metabolic, epigenetic).
- Analysis of how reprogramming enhances cellular fitness, tumor infiltration, and payload delivery.
- Assessment of design criteria for clinical controllability, safety, and scalability.
Main Results:
- Immune cell reprogramming improves LCDDSs' tumor infiltration, payload transport, and release profiles.
- Reprogramming mitigates immune cell exhaustion and enhances adaptability to hostile TMEs.
- Engineered LCDDSs demonstrate potential for precise targeting with reduced systemic toxicity.
Conclusions:
- Immune cell reprogramming is a key strategy to overcome current LCDDS limitations.
- Reprogrammed LCDDSs offer a versatile platform for advanced precision oncology treatments.
- Integrating immune cell engineering with drug delivery technologies promises improved cancer therapeutics.
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