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A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research
Published on: August 15, 2019
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Monocytes engineered with iSNAP inhibit human B-lymphoma progression
Haohsiang Wu1,2, Siamak Amirfakhri3,4, Hsin-Hung Lin1
1Department of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USA.
Bioengineering & Translational Medicine
|May 23, 2022
Summary
Engineered monocytes (iSNAP-MC) were developed to block the CD47-SIRPα "Don't eat me" signal, enhancing anti-tumor immunity. These modified monocytes suppressed tumor growth in mice, offering a novel cancer immunotherapy approach.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Monocytes are key immune regulators involved in homeostasis and cancer progression.
- The CD47-SIRPα interaction acts as a "Don't eat me" signal, inhibiting phagocytosis by monocytes and macrophages.
- Targeting immune coinhibitory signals presents a strategy for cancer immunotherapy.
Purpose of the Study:
- To engineer human monocytes to activate immune responses against cancer.
- To investigate the functional changes in monocytes engineered to rewire the CD47-SIRPα axis.
- To evaluate the therapeutic potential of engineered monocytes in a murine tumor model.
Main Methods:
- Development of integrated sensing and activating proteins (iSNAPs) to create iSNAP-monocytes (iSNAP-MC).
- Analysis of monocyte/macrophage marker expression (CD11b, CD14, CD31) in engineered monocytes.
- Assessment of macrophage activation markers (CD86, CD80, CD206) and TNFα production in PMA-induced iSNAP-MC-derived macrophages (iSNAP-MΦ).
- In vivo evaluation of iSNAP-MC efficacy in suppressing human B-lymphoma tumors in mice.
Main Results:
- Engineered iSNAP-monocytes (iSNAP-MC) exhibited upregulated expression of monocyte/macrophage markers.
- iSNAP-MΦ displayed enhanced expression of activation markers CD86 and CD80, along with increased TNFα.
- Injection of iSNAP-MC led to significant suppression of tumor progression in mice bearing human B-lymphoma.
- The engineered monocytes effectively blocked coinhibitory immune signals by rewiring the CD47-SIRPα axis.
Conclusions:
- Rewiring the CD47-SIRPα axis in monocytes creates potent anti-cancer immune cells.
- Engineered monocytes (iSNAP-MC) demonstrate therapeutic potential for cancer immunotherapy.
- This approach offers a novel strategy to overcome immune evasion in tumors.
