ArticlePloS one2013
The natural human IgM antibody PAT-SM6 induces apoptosis in primary human multiple myeloma cells by targeting heat shock protein GRP78.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Targeting the unfolded protein response in cancer: exploiting endoplasmic reticulum stress for therapeutic intervention.Biochemical pharmacology · 2025Review
- IgE based therapeutics are an emerging modality in cancer treatment.Discover oncology · 2025Review
- Defining the Features of Complement-Active IgM.Journal of molecular biology · 2025Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Harnessing IgM for solid tumor therapy: biology, engineering advances, and translational challenges.Frontiers in immunology · 2025Review
- Targeting the epidermal growth factor receptor using IgM antibodies: toward next generation cancer immunotherapy.Frontiers in immunology · 2025Article
- The role of B-1 cells in cancer progression and anti-tumor immunity.Frontiers in immunology · 2024Review
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence.Cancer metastasis reviews · 2023Review
- Endoplasmic Reticulum Stress and Cancer: Could Unfolded Protein Response Be a Druggable Target for Cancer Therapy?International journal of molecular sciences · 2023Review
- Vulnerability of The Male Reproductive System to SARS-CoV-2 Invasion: Potential Role for The Endoplasmic Reticulum Chaperone Grp78/HSPA5/BiP.Cell journal · 2022Article
- The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.Nature communications · 2022Article
- Review
- Peroxidase from foxtail millet bran exerts anti-colorectal cancer activityActa pharmaceutica Sinica. B · 2022Article
- Isotype selection for antibody-based cancer therapy.Clinical and experimental immunology · 2021Review
- Overcoming drug resistance by targeting protein homeostasis in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- The HSP Immune Network in Cancer.Frontiers in immunology · 2021Review
- Not all therapeutic antibody isotypes are equal: the case of IgMChemical science · 2020Article
- Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models. A Review.Frontiers in immunology · 2020Review
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM.
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