Immunomodulating Multi-antibody-modified Exosome Service

Modulation against immune checkpoints and related molecules is one of the functions of the multi-specific antibody-modified exosomes that are available at Creative Biolabs. We are able to control the usual immunological effects of exosome engineering by organizing and combining different antibodies to immunomodulatory molecules and altering them on exosome membranes via genetic engineering or surface coupling.

Introduction of Immunomodulating Multi-Specific Antibody-Modified Exosomes

Cancer treatment has undergone a paradigm shift thanks to immunotherapy, and several new immunomodulatory targets, including PD-L1, CD3, and OX40, have been identified. On the one hand, immune checkpoint inhibitors have become increasingly significant in the treatment of cancer, dramatically enhancing prognosis and survival. For example, the interaction of PD-1 with PD-L1 has been detected in a variety of cancers, where expression of PD-1 on T cells suppresses immunity and enhances the growth of different types of PD-L1-positive tumors. In contrast, PD-1 modification on exosomes was found to compete for binding PD-L1 and to have stronger and more stable immunotoxic effects than its soluble form. Anti-CD3-modified exosomes induce the proliferation of resting CD3⁺ T cells and increase their cytokine and chemokine levels, triggering the release of cytotoxins into cancer cells and leading to cell death. OX40L-modified exosomes bind OX40 and deliver co-stimulatory signals to activate the classical NF-κB1 pathway or non-classical NF-κB2 pathway, PI3k/PKB, and NFAT pathways, thereby promoting effector T cell survival, memory T cell expansion and expression of cytokine receptor-related genes to enhance immune system response.

Immunomodulating Multi-antibody-modified Exosome Engineering Strategy

Exosomes have a different lipid composition than the plasma membrane, suggesting a different and more complex origin than simple membrane outgrowth. They contain proteins that are retained from the primary cell through biogenesis, based on which the primary cell can be genetically modified to produce the desired exosome. Co-expression of the aforementioned immunomodulatory antibodies/ligands and antibodies to tumor-specific membrane proteins onto exosomes can specifically pull T cells and tumor cells together to develop a cutting-edge approach for therapy. In particular, considering the potential impact of individual antibody tropism on the physicochemical and biological properties of engineered exosomes, by aligning the V_H and V_L of these single-chain antibodies in different orientations and junctioning them with flexible peptides, these antibodies achieve the display of exosomal surface through membrane proteins as a fusion scaffold, directing the killing toxicity of immune cells.

Fig.1 Multi-antibody-modified exosome. (Shi, 2020)

Creative Biolabs provides innovative engineering modification services for the expression of antibodies to immunomodulatory molecules and antibodies to cancer cell-positive proteins on exosomes, significantly improving the degree of response to exosome-induced immunity. Please contact us to learn more.

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