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HemaCare PBMCs Power Exosome-based Cancer Immunotherapy

Mar 3, 2020 10:02:00 AM / by Nancy Andon, MSc

Immunotherapy word cloud_AdobeStock_140412255-1In a recent study, scientists at UCLA medical school cited using HemaCare sourced PBMCs for their research into a novel cancer immunotherapy strategy. [1]

This promising new strategy is based on cellular structures known as exosomes, which are small membrane-bound packets used to deliver protein “messages” from cell to cell. Because exosomes are known to facilitate cell-to-cell communications, researchers were keen to figure out whether they could be used to communicate the information immune cells need to target cancer.

Breast cancer, long acknowledged to be one of the most prevalent and dangerous forms of cancer, is the subject of intensive medical research. Studies have shown that a cell surface protein known as HER2 is a marker for a particularly aggressive form of breast cancer. With that fact in mind, UCLA researchers set out to design an exosome-driven platform that targets the HER2 protein on cancer cells, as well as CD3, a well-known surface marker for cytotoxic T cells. They used genetic engineering to create designer exosomes--known as SMART-Exos--displaying both anti-human CD3 and anti-human HER2 antibodies on their surface.

To test their platform, the authors acquired human peripheral blood mononuclear cells (PBMCs) sourced from HemaCare. HemaCare PBMCs are isolated from leukopaks collected from highly characterized donors according to strict regulatory requirements and industry best practices.

The authors performed in vitro cytotoxicity assays, by testing their SMART-Exos in the presence of human PBMCs as a source of CD3+ T cells, along with HER2+ breast cancer cell lines. The SMART-Exos showed consistent efficacy in killing HER2+ cancer cells which was dependent on the level of HER2 expression. In the presence of CD3-depleted human PBMCs, the addition of SMART-Exos resulted in minimal cytotoxicity against HER2+ cells.

Image Credit - Shi X, et al. Molecular Therapy 1-12-2019Anti-CD3/anti-HER2 SMART-Exosomes are designed to target HER2+ breast cancer cells. Image credit: Shi X, et al. Molecular Therapy. 1-12. 2019.

The authors also tested their platform in vivo. Mice bearing human HER2+ breast cancer cells were engrafted with human PBMCs. In the presence of human PBMCs, SMART-Exos induced potent cytotoxicity against HER2+ cells, resulting in significant inhibition of tumor growth.

If exosome-based cancer immunotherapy turns out to be a successful clinical strategy, it will have several advantages over current CAR T based immunotherapies. Exosome-based drug delivery has already been shown to have an excellent safety profile, due to the fact that human cell-derived exosomes are unlikely to trigger an immune response. Targeting is also more direct than with current cancer immunotherapy platforms, making clinical application more controllable.

For more information on human PBMCs and other HemaCare products, please visit our website here.

Reference:

  1. Shi X, et al. Genetically Engineered Cell-Derived Nanoparticles for Targeted Breast Cancer Immunotherapy. Molecular Therapy. 1-12. 2019.

 

Topics: Cancer, PBMCs, Immunotherapy (Immunology)

Nancy Andon, MSc

Written by Nancy Andon, MSc

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