In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer
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Therapeutic monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting an NK cell-mediated anti-tumor response. The IgG1 mAb cetuximab has been used for treatment of RASwt metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e. activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell derived NK cells (UCB-NK). While cetuximab monotherapy was not effective against EGFR- RASwt, EGFR+ RASmut and EGFR+ BRAFmut cells, A-PBNK were able to initiate lysis of EGFR+ colon cancer cells irrespective of RAS or BRAF status. Cytotoxic effects of A-PBNK (but not UCB-NK) were further potentiated significantly by coating EGFR+ colon cancer cells with cetuximab. Of note, a significantly higher cytotoxicity was induced by UCB-NK in EGFR-RASwt (42 ± 8% versus 67 ± 7%), EGFR+ RASmut (20 ± 2% versus 37 ± 6%) and EGFR+ BRAFmut (23 ± 3% versus 43 ± 7%) colon cancer cells compared to A-PBNK and equaled the cytotoxic efficacy of the combination of A-PBNK and cetuximab. The anti-tumor efficacy of UCB-NK cells against cetuximab resistant human EGFR+ RASmut colon cancer cells was further confirmed in an in vivo preclinical mouse model where UCB-NK showed enhanced anti-tumor cytotoxicity against colon cancer independent of EGFR and RAS status. As UCB-NK have been proven safe in a recently conducted phase I clinical trial in acute myeloid leukemia, a fast translation into clinical proof of concept for mCRC could be considered.
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UCB-NK cells increased antitumour cytotoxicity against CRC regardless of the status of EGFR and RAS in a mouse model.
“Another preclinical study using a mouse model reported that umbilical cord blood stem cell-derived NK (UCB-NK) cells increased antitumour cytotoxicity against CRC regardless of the status of EGFR and RAS [53].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [53]
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Immune Targets in Colorectal Cancer
Dariya, B., & Nagaraju, G. P. (2020) · Diagnostics and therapeutic advances in GI malignancies · doi:10.1007/978-981-15-6487-1_12
Case Report: Feasibility and Safety of Autologous NK Cell Therapy in Patients with Cancer
Nilubol, S., Kitisakronnakorn, W., & Naigovit, P. (2021) · Journal of Cancer Therapy · doi:10.4236/jct.2021.1212063
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Establishment of Humanized Mice And Its Application Progress in Cancer Immunotherapy
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Cell-Based Therapies in Cancer
Hernández, A., & Mukherjee, S. (2024) · Synthesis lectures on biomedical engineering · doi:10.1007/978-3-031-50844-8_4
On the TRAIL of a killer: mechanisms of action of an allogeneic NK cell therapy
van Vliet, A. A. (2024) · doi:10.5463/thesis.720
Humanized Mice as Models to study Human Innate Immunity and Immunotherapies
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- Authors
- Veluchamy, J. P., Lopez-Lastra, S., Spanholtz, J., Bohme, F., Kok, N., Heideman, D. A. M., Verheul, H. M. W., Di Santo, J. P., de Gruijl, T. D., & van der Vliet, H. J.
- Affiliations
- Cancer Center Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-02-06
- Volume
- 8
- Pages
- 87-87
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5292674
- OpenAlex
- W2586986504
- Cited by
- 54
- References
- 47
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 13 · 2020: 7 · 2019: 3 · 2018: 7 · 2017: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-INBS-0006)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- adoptive NK cell therapy, metastatic colorectal cancer, cetuximab, EGFR, RAS mutations, BRAF mutation, cetuximab resistance, allogeneic NK cells, NK cell cytotoxicity, antitumor immunity
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