2. Academic Validation
  3. Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo

Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo

  • Mol Cancer Ther. 2021 Oct;20(10):1941-1955. doi: 10.1158/1535-7163.MCT-21-0035.
Rocio Montes de Oca 1,  Alireza S Alavi 2,  Nick Vitali 2,  Sabyasachi Bhattacharya 2,  Christina Blackwell 2,  Krupa Patel 2,  Laura Seestaller-Wehr 2,  Heather Kaczynski 2,  Hong Shi 2,  Eric Dobrzynski 3,  Leslie Obert 4,  Lyuben Tsvetkov 2,  David C Cooper 5,  Heather Jackson 2,  Paul Bojczuk 2,  Sabrina Forveille 6 7,  Oliver Kepp 6 7,  Allan Sauvat 6 7,  Guido Kroemer 6 7 8 9 10,  Mark Creighton-Gutteridge 11,  Jingsong Yang 2,  Chris Hopson 2,  Niranjan Yanamandra 2,  Christopher Shelton 2,  Patrick Mayes 2,  Joanna Opalinska 12,  Mary Barnette 2,  Roopa Srinivasan 13,  James Smothers 2,  Axel Hoos 12
Affiliations

Affiliations

  • 1 Experimental Medicine Unit, Oncology R&D, GlaxoSmithKline, Collegeville, Pennsylvania. maria-del-rocio.x.montes-de-oca-ruiz@gsk.com.
  • 2 Immuno-Oncology and Combinations RU, Oncology R&D, GlaxoSmithKline, Collegeville, Pennsylvania.
  • 3 Bioanalysis, Immunogenicity and Biomarkers, GlaxoSmithKline, Collegeville, Pennsylvania.
  • 4 Translational Medicine and Comparative Pathobiology, GlaxoSmithKline, Collegeville, Pennsylvania.
  • 5 Research Statistics, GlaxoSmithKline, Collegeville, Pennsylvania.
  • 6 Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
  • 7 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France.
  • 8 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
  • 9 Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, P.R. China.
  • 10 Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
  • 11 Cell Therapy RU, Oncology R&D, GlaxoSmithKline, Hertfordshire, United Kingdom.
  • 12 Oncology R&D, GlaxoSmithKline, Collegeville, Pennsylvania.
  • 13 Experimental Medicine Unit, Oncology R&D, GlaxoSmithKline, Collegeville, Pennsylvania.
PMID: 34253590 DOI: 10.1158/1535-7163.MCT-21-0035
Abstract

B-cell maturation antigen (BCMA) is an attractive therapeutic target highly expressed on differentiated plasma cells in multiple myeloma and Other B-cell malignancies. GSK2857916 (belantamab mafodotin, BLENREP) is a BCMA-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory multiple myeloma. We report that GSK2857916 induces immunogenic cell death in BCMA-expressing Cancer cells and promotes dendritic cell activation in vitro and in vivo GSK2857916 treatment enhances intratumor immune cell infiltration and activation, delays tumor growth, and promotes durable complete regressions in immune-competent mice bearing EL4 lymphoma tumors expressing human BCMA (EL4-hBCMA). Responding mice are immune to rechallenge with EL4 parental and EL4-hBCMA cells, suggesting engagement of an adaptive immune response, immunologic memory, and tumor antigen spreading, which are abrogated upon depletion of endogenous CD8+ T cells. Combinations with OX40/OX86, an immune agonist antibody, significantly enhance antitumor activity and increase durable complete responses, providing a strong rationale for clinical evaluation of GSK2857916 combinations with immunotherapies targeting adaptive immune responses, including T-cell-directed checkpoint modulators.

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