A Phase I Trial of Autologous Tumour Vaccine for Advanced Solid Cancers
Phase 1 trial to evaluate the feasibility of preparation, safety, tolerability and response to a personalised autologous tumour vaccine (ATV) formulated with Advax adjuvant when administered to patients with advanced solid cancers either as monotherapy or in combination with other standard of care agents
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer: a Phase II Study
Single-arm, monocentric trial to assess safety and immunological efficacy of adjuvant vaccination with autologous dendritic cells loaded with autologous tumour homogenate after curative resection for stage IV colorectal cancer
GM-CSF and IL-7 fusion cytokine engineered tumor vaccine generates long-term Th-17 memory cells and increases overall survival in aged syngeneic mouse models of glioblastoma.
作者: Jack M Shireman ; Nikita Gonugunta ; Lei Zhao ; Akshita Pattnaik ; Emily Distler ; Skyler Her ; Xiaohu Wang ; Rahul Das ; Jaques Galipeau ; Mahua Dey
Age-related immune dysfunctions, such as decreased T-cell output, are closely related to pathologies like cancers and lack of vaccine efficacy among the elderly. Engineered fusokine, GIFT-7, a fusion of interleukin 7 (IL-7) and GM-CSF, can reverse aging-related lymphoid organ atrophy. We generated a GIFT-7 fusokine tumor vaccine and employed it in aged syngeneic mouse models of glioblastoma and found that peripheral vaccination with GIFT-7TVax resulted in thymic regeneration and generated durable long-term antitumor immunity specifically in aged mice. Global cytokine analysis showed increased pro-inflammatory cytokines including IL-1β in the vaccinated group that resulted in hyperactivation of dendritic cells. In addition, GIFT-7 vaccination resulted in increased T-cell trafficking to the brain and robust Th-17 long-term effector memory T-cell formation. TCR-seq analysis showed increased productive frequency among detected rearrangements within the vaccinated group. Overall, our data demonstrate that aging immune system can be therapeutically augmented to generate lasting antitumor immunity.
2022-11-02·Small (Weinheim an der Bergstrasse, Germany)
Tumor Microenvironment-Activated Hydrogel Platform with Programmed Release Property Evokes a Cascade-Amplified Immune Response against Tumor Growth, Metastasis and Recurrence.
作者: Songlin Gong ; Xiuqi Liang ; Miaomiao Zhang ; Lu Li ; Tao He ; Yuan Yuan ; Xinchao Li ; Furong Liu ; Xi Yang ; Meiling Shen ; Qinjie Wu ; Changyang Gong
In situ tumor vaccines (ITV) have been recognized as a promising antitumor strategy since they contain the entire tumor-specific antigens, avoiding tumor cells from evading immune surveillance due to antigen loss. However, the therapeutic benefits of ITV are limited by obstacles such as insufficient antigen loading, inadequate immune system activation, and immunosuppressive tumor microenvironments (TME). Herein, a tumor microenvironment-activated hydrogel platform (TED-Gel) with programmed drug release property is constructed for cascaded amplification of the anti-tumor immune response elicited by ITV. Both doxorubicin (Dox) and cytosine-phosphate-guanosine oligodeoxynucleotides (CpG) are released first, in which Dox induces immunogenic tumor cell death causing additional tumor antigen release and leading the dying primary tumor cells into autologous tumor vaccine, and the released CpG promotes antigen presenting cell activation. Subsequently, the decomposed scaffold materials in conjunction with CpG, turn the anti-inflammatory M2-like macrophages into the M1 type, reversing the immunosuppressive TME. With decomposition of the TED-Gel, large amounts of macromolecule anti-PD-L1 antibodies are liberated, reinvigorating the exhausted effector T cells. In vivo studies demonstrate that TED-Gel significantly inhibits the primary, distant and rechallenged tumor growth. Overall, the simple and powerful TED-Gel provides an alternative strategy for the future development of tumor vaccines with broad application.