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Cited by 807Immune Cell Function and InteractionMultiple Myeloma Research and TreatmentsCancer Immunotherapy and Biomarkers

The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody

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Benson, Don M., Bakan, Courtney E., Mishra, Anjali, Hofmeister, Craig C., Efebera, Yvonne, Becknell, Brian, Baiocchi, Robert A., Zhang, Jianying +9 more·2010·Blood
DOI 10.1182/blood-2010-02-271874PMC PMC3490105
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Abstract

T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti-PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1(+) MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered.

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  • Blocking the PD-1/PD-L1 axis in multiple myeloma has potential therapeutic effects, as shown in cell lines and animal models.

    “In fact, many studies have been conducted on cell lines and animal models in this context and have shown that blocking the PD 1/PD L1 axis in multiple myeloma has potential therapeutic effects [203–206].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [203]

    The Figure 5 findings report that the anti-PD-1 antibody CT-011 enhanced NK-cell activity against a multiple myeloma cell line and primary human myeloma cells, supporting therapeutic potential. The paper does not report an animal-model test of PD-1/PD-L1 blockade in multiple myeloma, so it does not support that part of the citing sentence. Page numbers were not available for these indexed passages. (LLM, conf=0.85)

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Authors
Benson, D. M., Bakan, C. E., Mishra, A., Hofmeister, C. C., Efebera, Y., Becknell, B., Baiocchi, R. A., Zhang, J., Yu, J., Smith, M. K., Greenfield, C. N., Porcu, P., Devine, S. M., Rotem-Yehudar, R., Lozanski, G., Byrd, J. C., & Caligiuri, M. A.
Affiliations
  • The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
  • Nationwide Children's Hospital (US)
  • The Ohio State University Wexner Medical Center (US)
  • CureTech Ltd, Yavne, Israel; and
  • The Ohio State University (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2010-09-30
Volume
116
Issue
13
Pages
2286-2294
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2010-02-271874
PMC
PMC3490105
OpenAlex
W2022580424
Cited by
807
References
54
Citations by year
2026: 9 · 2025: 27 · 2024: 27 · 2023: 52 · 2022: 56 · 2021: 88 · 2020: 97 · 2019: 76 · 2018: 83 · 2017: 63 · 2016: 63 · 2015: 56 · 2014: 30 · 2013: 31 · 2012: 30
FWCI
10.73
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Research Resources (UL1RR025755)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
PD-1/PD-L1 axis, natural killer cells, multiple myeloma, anti-PD-1, lenalidomide, NK cell cytotoxicity, NK cell trafficking, immune complex formation, combination immunotherapy
MeSH terms
Lenalidomide, Antibodies, Monoclonal, Antigen-Antibody Complex, Antineoplastic Agents, Cytotoxicity, Immunologic, Humans, Interferon-gamma, Killer Cells, Natural, Multiple Myeloma, Thalidomide, Signal Transduction, Down-Regulation, Antigens, CD, Receptors, CXCR4, K562 Cells, Cell Line, Tumor, Apoptosis Regulatory Proteins, Chemokine CXCL12, B7-H1 Antigen, Programmed Cell Death 1 Receptor, In Vitro Techniques

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