Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial

Evanthia Galanis (), Katharine E. Dooley, S. Keith Anderson, Cheyne B. Kurokawa, Xiomara W. Carrero, Joon H. Uhm, Mark J. Federspiel, Alexey A. Leontovich, Ileana Aderca, Kimberly B. Viker, Julie E. Hammack, Randolph S. Marks, Steven I. Robinson, Derek R. Johnson, Timothy J. Kaufmann, Jan C. Buckner, Daniel H. Lachance, Terry C. Burns, Caterina Giannini, Aditya Raghunathan, Ianko D. Iankov and Ian F. Parney
Additional contact information
Evanthia Galanis: Division of Medical Oncology, Mayo Clinic
Katharine E. Dooley: Mayo Clinic
S. Keith Anderson: Mayo Clinic
Cheyne B. Kurokawa: Mayo Clinic
Xiomara W. Carrero: Mayo Clinic
Joon H. Uhm: Division of Neuro-Oncology, Mayo Clinic
Mark J. Federspiel: Mayo Clinic
Alexey A. Leontovich: Mayo Clinic
Ileana Aderca: Mayo Clinic
Kimberly B. Viker: Mayo Clinic
Julie E. Hammack: Division of Neuro-Oncology, Mayo Clinic
Randolph S. Marks: Division of Medical Oncology, Mayo Clinic
Steven I. Robinson: Division of Medical Oncology, Mayo Clinic
Derek R. Johnson: Mayo Clinic
Timothy J. Kaufmann: Mayo Clinic
Jan C. Buckner: Division of Medical Oncology, Mayo Clinic
Daniel H. Lachance: Division of Neuro-Oncology, Mayo Clinic
Terry C. Burns: Mayo Clinic
Caterina Giannini: Mayo Clinic
Aditya Raghunathan: Mayo Clinic
Ianko D. Iankov: Mayo Clinic
Ian F. Parney: Mayo Clinic

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = −0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.

Date: 2024
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DOI: 10.1038/s41467-023-43076-7

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