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

Abstract

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.

• Authors: Nandakumar Packiriswamy, Deepak Upreti, Yumei Zhou, Rehan Khan, Amber Miller, Rosa M Diaz, Cliona M Rooney, Angela Dispenzieri, Kah-Whye Peng, Stephen J Russell
• Journal: Leukemia (Leukemia) Vol. 34 Issue 12 Pg. 3310-3322 (12 2020) ISSN: 1476-5551 [Electronic] England
• PMID: 32327728 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Symporters
• sodium-iodide symporter

Topics

• Antigens, Neoplasm (immunology)
• Cells, Cultured
• Humans
• Leukocytes, Mononuclear
• Measles virus (immunology)
• Multiple Myeloma (immunology, therapy)
• Oncolytic Virotherapy (methods)
• Oncolytic Viruses (immunology)
• Symporters (immunology)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Cytotoxic (immunology)