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

Nandakumar Packiriswamy, Deepak Upreti, Yumei Zhou, Rehan Khan, Amber Miller, Rosa M. Diaz, Cliona M. Rooney, Angela Dispenzieri, Kah Whye Peng, Stephen J. Russell

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Jan 1 2020

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ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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