- Gastrointestinal cancer
-
First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer
-
Minkyu Jung, Jii Bum Lee, Hyo Song Kim, Woo Sun Kwon, Hyun Ok Kim, Sinyoung Kim, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Hyun Cheol Chung, Sun Young Rha
-
Cancer Res Treat. 2024;56(1):208-218. Published online June 28, 2023
-
DOI: https://doi.org/10.4143/crt.2022.1328
-
-
 Abstract
 PDF Supplementary Material PubReader ePub
- Purpose
BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials and Methods
Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses.
Results
Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients.
Conclusion
BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.
-
Citations
Citations to this article as recorded by  - HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments
Magdalena K. Scheck, Ralf D. Hofheinz, Sylvie Lorenzen
Cancers.2024; 16(7): 1336. CrossRef
-
3,220
View
-
195
Download
-
1
Web of Science
-
1
Crossref
|
KCA
