HELLO? IS THERE ANTIBODY OUT THERE?

by Heather Diogo

Cancer remains one of the leading causes of death worldwide, despite the range of treatment options available. Toxic side effects are one of the primary limitations of chemotherapy. A novel cancer treatment strategy called immunotherapy has recently caught the eye of many researchers around the globe, due to its potential to improve treatment standards and outcomes.

Liu et al. are one such group. They engineered cell membrane-derived “vesicular antibodies” (VAs), with the aim of enhancing the therapeutic index and efficacy of anticancer drugs by combining targeted drug delivery with immunotherapy.

In order to do this, a cell line is genetically engineered to stably overexpress a full-length monoclonal antibody on its cell membrane. A vesicle that has antibodies on its surface is produced from the cell membrane and loaded with an anticancer drug before injection into the patient.

The antibody on the vesicle surface is specific for a tumour cell antigen, so is able to guide the vesicle to a tumour cell and bind its antigen. The membrane of the vesicle fuses with the tumour cell membrane and this releases the drug into the tumour cell to exert its cytotoxic effects. At the same time, the antibodies are transferred on to the tumour cell membrane. These antibodies are able to recruit natural killer (NK) cells of the immune system to aggregate into the tumour microenvironment. The NK cells are able to kill the tumour cells through antibody-dependent cellular cytotoxicity, leading to tumour necrosis.

Figure 1: Schematic diagram of vesicular antibody (VA) production and associated delivery to and response of target cell. Adapted from “Vesicular Antibodies: A Bioactive Multifunctional Combination Platform for Targeted Therapeutic Delivery and Cancer Immunotherapy”, by Liu et al., 2019, Advanced Materials, 31(17):1808294. Copyright 2019 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

In the proof-of-principle study, the VAs were shown to specifically target tumour cells and not normal cells in both cell culture and mouse models. Uptake of drug by tumour cells was higher in the form of the VA relative to free drug, and the same was found to be true for drug efficacy. Finally, immune cells could successfully bring about antibody-dependent cellular cytotoxicity in tumour cells after activation by the VAs.

All in all, vesicular antibodies seem to be a promising anticancer platform to reduce toxicity and improve efficacy by combining targeted drug delivery with immunotherapy. Definitely something to look out for in the future!

References:

Liu X, Liu C, Zheng Z, Chen S, Pang X, Xiang X, et al. Vesicular Antibodies: A Bioactive Multifunctional Combination Platform for Targeted Therapeutic Delivery and Cancer Immunotherapy. Adv Mater. 2019 Apr;31(17):1808294.

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