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Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

ABSTRACT: The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a 'middle' approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.

SUBMITTER: Chew CH

PROVIDER: S-EPMC7281484 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

Chew Chee Ho CH Lee Chih-Wei CW Huang Wan-Ting WT Cheng Li-Wei LW Chen Amanda A Cheng Tsai-Mu TM Liu Yen-Lin YL Chen Chien-Chung CC

Membranes 20200426 5

The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale ...[more]

PMID: 32357523

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Project description:BackgroundSelective cancer cell recognition is the most challenging objective in the targeted delivery of anti-cancer agents. Extruded specific cancer cell membrane coated nanoparticles, exploiting the potential of homotypic binding along with certain protein-receptor interactions, have recently proven to be the method of choice for targeted delivery of anti-cancer drugs. Prediction of the selective targeting efficiency of the cancer cell membrane encapsulated nanoparticles (CCMEN) is the most critical aspect in selecting this strategy as a method of delivery.Materials and methodsA probabilistic model based on binding scores and differential expression levels of Glioblastoma cancer cells (GCC) membrane proteins (factors and receptors) was implemented on python 3.9.1. Conditional binding efficiency (CBE) was derived for each combination of protein involved in the interactions. Selective propensities and Odds ratios in favour of cancer cells interactions were determined for all the possible combination of surface proteins for 'k' degree of interaction. The model was experimentally validated by two types of Test cultures.ResultsSeveral Glioblastoma cell surface antigens were identified from literature and databases. Those were screened based on the relevance, availability of expression levels and crystal structure in public databases. High priority eleven surface antigens were selected for probabilistic modelling. A new term, Break-even point (BEP) was defined as a characteristic of the typical cancer cell membrane encapsulated delivery agents. The model predictions lie within ±7% of the experimentally observed values for both experimental test culture types.ConclusionThe implemented probabilistic model efficiently predicted the directional preference of the exposed nanoparticle coated with cancer cell membrane (in this case GCC membrane). This model, however, is developed and validated for glioblastoma, can be easily tailored for any type of cancer involving CCMEN as delivery agents for potential cancer immunotherapy. This probabilistic model would help in the development of future cancer immunotherapeutic with greater specificity.

Dataset Information

Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

Publications

Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

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