A phase 1 trial evaluated the safety, toxicity, and efficacy of an oncolytic measles virus (MV) derivative expressing carcinoembryonic antigen (MV-CEA) in patients with recurrent glioblastoma (GBM). The study enrolled 22 patients, with 9 in Group A (MV-CEA administered into the resection cavity) and 13 in Group B (intratumoral MV-CEA on day 1 followed by resection cavity administration on day 5). The maximum tolerated dose (MTD) was determined to be 10⁷ TCID50 for Group A and 2×10⁷ TCID50 for Group B. The treatment was well tolerated with no dose-limiting toxicity observed. Median overall survival (OS) was 11.6 months, with 45.5% one-year survival, which was favorable compared to contemporary controls. Secondary endpoints included assessments of viral replication, immune response, and tumor microenvironment remodeling. A 22-gene interferon-stimulated gene (ISG) diagonal linear discriminant analysis (DLDA) algorithm was found to be inversely correlated with viral replication and tumor microenvironment remodeling, including proinflammatory changes and CD8+ T cell infiltration. GBM is the most common and aggressive malignant brain tumor with a poor prognosis. Current treatments have limited efficacy, and immunotherapy has not shown consistent clinical activity. Oncolytic viruses, including attenuated measles virus, are being explored as novel immunotherapies due to their potential for tumor selectivity and safety. MV-based virotherapy has shown promise in preclinical models and early clinical trials. The study demonstrated that MV-CEA was safe up to the maximum feasible dose and resulted in proinflammatory tumor remodeling. The DLDA algorithm, based on ISG expression, predicted viral replication and could guide treatment personalization. The study also showed that MV-CEA induced significant CD8+ T cell infiltration and immune response in post-treatment samples. Median progression-free survival (PFS) was similar between the two groups, with 3.0 and 3.4 months, respectively. Median OS was also similar, with 11.8 and 11.4 months, respectively. The study found that patients with higher ISG DLDA scores had lower viral replication, suggesting that ISG expression could be used to identify patients likely to benefit from MV therapy. The results support further clinical investigation of oncolytic MV derivatives and the use of ISG-based algorithms for treatment personalization. The study highlights the potential of MV-based virotherapy in GBM and the importance of patient selection based on molecular profiles.A phase 1 trial evaluated the safety, toxicity, and efficacy of an oncolytic measles virus (MV) derivative expressing carcinoembryonic antigen (MV-CEA) in patients with recurrent glioblastoma (GBM). The study enrolled 22 patients, with 9 in Group A (MV-CEA administered into the resection cavity) and 13 in Group B (intratumoral MV-CEA on day 1 followed by resection cavity administration on day 5). The maximum tolerated dose (MTD) was determined to be 10⁷ TCID50 for Group A and 2×10⁷ TCID50 for Group B. The treatment was well tolerated with no dose-limiting toxicity observed. Median overall survival (OS) was 11.6 months, with 45.5% one-year survival, which was favorable compared to contemporary controls. Secondary endpoints included assessments of viral replication, immune response, and tumor microenvironment remodeling. A 22-gene interferon-stimulated gene (ISG) diagonal linear discriminant analysis (DLDA) algorithm was found to be inversely correlated with viral replication and tumor microenvironment remodeling, including proinflammatory changes and CD8+ T cell infiltration. GBM is the most common and aggressive malignant brain tumor with a poor prognosis. Current treatments have limited efficacy, and immunotherapy has not shown consistent clinical activity. Oncolytic viruses, including attenuated measles virus, are being explored as novel immunotherapies due to their potential for tumor selectivity and safety. MV-based virotherapy has shown promise in preclinical models and early clinical trials. The study demonstrated that MV-CEA was safe up to the maximum feasible dose and resulted in proinflammatory tumor remodeling. The DLDA algorithm, based on ISG expression, predicted viral replication and could guide treatment personalization. The study also showed that MV-CEA induced significant CD8+ T cell infiltration and immune response in post-treatment samples. Median progression-free survival (PFS) was similar between the two groups, with 3.0 and 3.4 months, respectively. Median OS was also similar, with 11.8 and 11.4 months, respectively. The study found that patients with higher ISG DLDA scores had lower viral replication, suggesting that ISG expression could be used to identify patients likely to benefit from MV therapy. The results support further clinical investigation of oncolytic MV derivatives and the use of ISG-based algorithms for treatment personalization. The study highlights the potential of MV-based virotherapy in GBM and the importance of patient selection based on molecular profiles.