Abstract CT093: Vaccine immunotherapy by homologous antigenic loading as adjuvant therapy for glioblastoma: Ongoing phase I analysis
Authors: Joseph F. Georges, Mazen Zaher, Corey M. Mossop, Christopher J. Bilbao, Christina M. Clay, Sabina Amin, Hamza A. Shaikh, Akshar Trivedi, Wei Liu, Madhuri Namekar, Colby J. Hofferek, Keenan Ernste, Eva H. Schumann, Mia Vu, Damilola Oyewole-Said, Nalini Bisht, Jonathan Vazquez-Perez, Ashley M. Goralczyk, Lindsey Colman, Lynne S. Kohler, Thuy V. Cao, Ngozi Okereke, Benjamin L. Musher, Vinod Ravi, Jan O. Kemnade, Rodrick C. Zvavanjanja, Jay-Jiguang Zhu, Sigmund H. Hsu, Yoshua Esquenazi-Levy, Nitin Tandon, Alan Turtz, Vanaja Konduri, William Karl Decker
Journal: Cancer Research (2024)

Abstract Glioblastoma (GBM) is a devastating tumor of the central nervous system (CNS) for which median survival remains 14-18 months despite aggressive standard of care. Early clinical studies of dendritic cell (DC) vaccination for the adjuvant treatment of GBM previously suggested mild to moderate clinical benefit, but results were both inconsistent and inconclusive. Homologous antigenic loading is an ex vivo technique that leverages p38MAPK and mTORC1 signaling cascades to initiate powerful cDC1-like skewing in monocyte-derived DC, leading to downstream induction of CD161int CD8+ cytolytic memory effectors. Here we report ongoing results of a completed phase I clinical trial with minimal exclusion criteria in which dendritic cell vaccines were prepared through homologous antigenic loading and administered to newly-diagnosed patients bilaterally in the vicinity of the deep cervical lymph nodes, assisted by ultrasound sonography. Patients were additionally adjuvanted with six weeks of concurrent type I interferon. Four dose levels from 3.5 x 106 to 3.6 x 107 total vaccine cells were tested, none of which resulted in AEs &amp;gt; grade 2 attributable to the investigational regimen. Immunohistochemistry of tumors derived from early post-vaccination second resections displayed enhanced CD8+ T-cell infiltration and pathologic findings consistent with residual rather than relapsed GBM in 2/3 patients. Radiologic pseudoprogression was also routinely observed among patients of all cohorts. Analysis of post-vaccination circulating PBMC indicated expansion of both CD4+ and CD8+ central memory T-cell compartments (p&amp;lt;0.05 for each by student’s two-tailed t-test) as well as expansion of CD8+CD127+ T-cells (p&amp;lt;0.05 by student’s two tailed t-test) in 4/4 patients analyzed. With an average of 10.9 months follow-up, median survival of this largely MGMT promoter unmethylated cohort was not yet reached and was statistically greater (p&amp;lt;0.05 by log-rank[Mantle-Cox]) than that of matched historical controls. At the time of submission, 13/15 trial patients remained alive with ECOG &amp;lt;/= 2. The results suggest that modern dendritic cell vaccines are safe, potentially efficacious, and can be effectively integrated within existing standards of care. Citation Format: Joseph F. Georges, Mazen Zaher, Corey M. Mossop, Christopher J. Bilbao, Christina M. Clay, Sabina Amin, Hamza A. Shaikh, Akshar Trivedi, Wei Liu, Madhuri Namekar, Colby J. Hofferek, Keenan Ernste, Eva H. Schumann, Mia Vu, Damilola Oyewole-Said, Nalini Bisht, Jonathan Vazquez-Perez, Ashley M. Goralczyk, Lindsey Colman, Lynne S. Kohler, Thuy V. Cao, Ngozi Okereke, Benjamin L. Musher, Vinod Ravi, Jan O. Kemnade, Rodrick C. Zvavanjanja, Jay-Jiguang Zhu, Sigmund H. Hsu, Yoshua Esquenazi-Levy, Nitin Tandon, Alan Turtz, Vanaja Konduri, William Karl Decker. Vaccine immunotherapy by homologous antigenic loading as adjuvant therapy for glioblastoma: Ongoing phase I analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT093.