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Development of Stimuli-Responsive Nanoparticle-carrying T lymphocytes in the Fight against Cancer

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Attracting immune cells to tumours via magnets

Immunotherapy is in the spotlight of cancer treatment. European researchers propose to improve immune cell biodistribution to tumours using magnetic nanoparticles.

Health

Exploiting the immune system to tackle cancer is not a new concept. Numerous clinical trials have tested the potential of awakening or modulating the immune system against cancer using cytokines, antibodies and immune cells. Studies employing cancer-specific T lymphocytes engineered to express chimeric antigen receptors CAR T against haematological malignancies have generated favourable clinical outcomes. However, similar clinical trials against solid tumours highlight limitations associated with poor trafficking to the tumour and a hostile tumour microenvironment. Being able to guide and improve the survival of these cells would significantly enhance their clinical efficacy.

Hybrid magnetic T lymphocytes

Undertaken with the support of the Marie Skłodowska-Curie Actions (MSCA) programme, the CellularNanoMachines project wished to combine the best of the synthetic and biological worlds to improve immunotherapies. “Our goal was to control and modulate the in vivo behaviour of T lymphocytes through the use of nanoparticles,” explains the MSCA research fellow Javier Hernández-Gil. The team employed peripheral blood mononuclear cells and tested the possibility of incorporating iron oxide-based magnetic nanoparticles in these cells as a proof of concept. They exploited two options: attaching nanoparticles to cell surface receptors or having them internalised by cells using bioconjugate chemistry. The resultant ‘magnetic cells’ retained their function following the incorporation of nanoparticles and could be guided towards a magnet. Paramount to these efforts was the production of water-soluble nanoparticles. To achieve this, the team employed phospholipid-based micelles to encapsulate hydrophobic nanoparticles and render them suitable for incorporation into cells. The biocompatibility and excellent magnetic performance of the resultant nanoparticles had no impact on cell survival. Researchers focused on studying and understanding how nanoparticle-cell hybrids behave in animal models of cancer. Labelling and tracking the cells inside animals indicated improved targeting and more efficient circulation in tumours than control T lymphocytes. Researchers used different imaging techniques and demonstrated the potential of nanoparticle-immune cell hybrids for therapeutic applications.

The future for nanoparticle-immune cell hybrids

“The most important achievement of CellularNanoMachines is the realisation of implementing alternative functionalities in immune cells through nanoparticles,” emphasises Hernández-Gil. Nanoparticles offer a simple and accessible way to improve T lymphocyte trafficking to solid tumours, their overall biodistribution and anticancer performance. Being able to change the in vivo fate of immune cells using external magnets opens numerous possibilities in cell therapy, especially with cancer immunotherapy taking such centre stage in oncology. Future work involves going a step further from the initial project and developing a strategy for the design of smart cell-based machines, hybrid systems capable of producing synergistic effects between nanoparticles, small metal compounds and immune cells. The use of small metal compounds in the field of theranostics opens new avenues for the diagnosis and treatment of cancer. This strategy will address current unmet clinical needs in oncology by improving immune cell performance in available cellular therapies.

Keywords

CellularNanoMachines, nanoparticle, immune cells, cancer, hybrid, T lymphocytes, immunotherapy, biodistribution

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