Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma

• Published in: Leukemia Vol. 34; no. 12; pp. 3310 - 3322
• Main Authors: Packiriswamy, Nandakumar, Upreti, Deepak, Zhou, Yumei, Khan, Rehan, Miller, Amber, Diaz, Rosa M., Rooney, Cliona M., Dispenzieri, Angela, Peng, Kah-Whye, Russell, Stephen J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2020; Nature Publishing Group
• Subjects: 13/21; 13/31; 692/308/2779/109/1940; 692/308/575; 82/75; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - immunology; Cancer Research; Care and treatment; Cell death; Cells, Cultured; Critical Care Medicine; Cytotoxicity; Development and progression; Genetic aspects; Health aspects; Hematology; Humans; Immune checkpoint; Immune response; Immunogenicity; Immunosuppressive agents; Immunotherapy; Intensive; Internal Medicine; Iodides; Leukocytes, Mononuclear; Lymphocytes; Lymphocytes T; Measles; Measles virus - immunology; Medicine; Medicine & Public Health; Multiple myeloma; Multiple Myeloma - immunology; Multiple Myeloma - therapy; Oncology; Oncolysis; Oncolytic Virotherapy - methods; Oncolytic Viruses - immunology; Peripheral blood mononuclear cells; Remission; Sodium iodide; Sodium iodide symporter; Symporters - immunology; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; Telomerase reverse transcriptase; Therapy; Tumor antigens; Tumor cells; Tumors; Vaccines; Viruses; United States
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-020-0828-7

Oncolytic virus therapy leads to immunogenic death of virus-infected tumor cells and this has been shown in preclinical models to enhance the cytotoxic T-lymphocyte response against tumor-associated antigens (TAAs), leading to killing of uninfected tumor cells. To investigate whether oncolytic virotherapy can increase immune responses to tumor antigens in human subjects, we studied T-cell responses against a panel of known myeloma TAAs using PBMC samples obtained from ten myeloma patients before and after systemic administration of an oncolytic measles virus encoding sodium iodide symporter (MV-NIS). Despite their prior exposures to multiple immunosuppressive antimyeloma treatment regimens, T-cell responses to some of the TAAs were detectable even before measles virotherapy. Measurable baseline T-cell responses against MAGE-C1 and hTERT were present. Furthermore, MV-NIS treatment significantly ( P  < 0.05) increased T-cell responses against MAGE-C1 and MAGE-A3. Interestingly, one patient who achieved complete remission after MV-NIS therapy had strong baseline T-cell responses both to measles virus proteins and to eight of the ten tested TAAs. Our data demonstrate that oncolytic virotherapy can function as an antigen agnostic vaccine, increasing cytotoxic T-lymphocyte responses against TAAs in patients with multiple myeloma, providing a basis for continued exploration of this modality in combination with immune checkpoint blockade.