OncoTargets and Therapy (Aug 2020)
A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model
Abstract
Xin-Long Li,1,2,* Shan Zeng,1,2,* Hai-Ping He,1,2 Xu Zeng,1,2 Li-Lei Peng,1,2 Li-Gang Chen1,2 1Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Neurosurgery Clinical Medical Research Center of Sichuan Province, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Gang Chen; Li-Lei PengDepartment of Neurosurgery, Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou, Sichuan, People’s Republic of ChinaEmail [email protected]; [email protected]: Conventional immunotherapy for glioma is not only expensive but also demonstrates less-than-desired clinical efficacy. In this study, we evaluated the immunotherapeutic efficacy of a tumor cell lysate-based hybrid glioma vaccine developed using a molecular-based approach.Methods: First, the ability of the autologous (9L-cell lysate) and allogeneic (C6-cell lysate) vaccines against glioma, individually and in combination, to activate Fischer344 rat dendritic cells (DCs) was determined. Next, the activated DCs were co-cultured with T lymphocytes and screened for the optimal DC-to-T-cell ratio. The in vitro efficacy of the DC/T-cell vaccine formulations subjected to different immunogen treatments and co-cultured with glioma cells was evaluated based on glioma cell viability and monocyte chemoattractant protein (MCP)-2 and interferon (IFN)-γ secretion. Subsequently, the efficacy of the 9L + C6 hybrid vaccine was evaluated in 32 glioma rat models, randomly allocated to the following five treatment groups: blank control, tumor, vaccine treatment, thymosin treatment, and vaccine + thymosin treatment (combined treatment). Changes in survival duration, intracranial tumor volume, peripheral blood immune-cell (CD4+ T, CD8+ T, and natural killer [NK] cell) count, and serum cytokine (interleukin [IL]-2, IL-10) levels were assessed in these groups.Results: The hybrid vaccine demonstrated the highest glioma cell apoptosis and the lowest cell viability and promoted MCP-2 and IFN-γ secretion in vitro. The vaccine treatment and combined treatment groups demonstrated longer survival duration, lower intracranial tumor volume, and higher immune cell glioma tissue infiltration and IL-2 secretion than the untreated tumor group, indicating the vaccine’s good in vivo efficacy. Thymosin treatment had minimal effect in enhancing anti-glioma immunity.Conclusion: We demonstrated the feasibility of combining autologous and allogeneic tumor cell lysates to stimulate specific host cell immune response against glioma cells. The good clinical efficacy of our developed glioma hybrid vaccine in rat models suggests its potential clinical application.Keywords: tumor cell lysate, vaccine, glioma, molecular simulation, rat, immunotherapy
