Enhanced anti-tumor immunity ex vivo induced by GM-CSF gene transducted dendritic cell vaccine

2011 ◽  
Vol 10 (3) ◽  
pp. 178-182 ◽  
Author(s):  
Songbing He ◽  
Liang Wang ◽  
Kang Sun ◽  
Yanyun Zhang ◽  
Dechun Li
2012 ◽  
Vol 14 (3) ◽  
pp. 252-260 ◽  
Author(s):  
Pei Zhang ◽  
Jinyan Wang ◽  
Danan Wang ◽  
Huan Wang ◽  
Fengping Shan ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 40 ◽  
Author(s):  
Ananda Mookerjee ◽  
Michele Graciotti ◽  
Lana E. Kandalaft

In the last 20 years, dendritic cells (DCs) have been largely used as a platform for therapeutic vaccination in cancer patients. However, despite its proven safety and ability to induce cancer specific immune responses, the clinical benefits of DC-based immunotherapy are currently very limited. Thus, novel approaches are still needed to boost its efficacy. Our group recently showed that squaric acid treatment of antigens is an important adjuvant that can increase vaccine-induced downstream immune responses and therapeutic outcomes. Here we further improved this dendritic cell vaccine formulation by developing a new method for differentiating and maturing DCs from their bone marrow precursors. Our data demonstrate that bone marrow-derived DCs differentiated with GM-CSF and IL-15 and matured with a maturation cocktail in two steps present a more mature and immunogenic phenotype, compared to standard DC preparations. Further suppression of the prostaglandin E2 pathway achieved even more immunogenic DC phenotypes. This vaccine was more potent at delaying tumor growth, improved animal survival and induced a more immunogenic and Th1-skewed T cell response in an ovarian cancer mouse model. These promising results support future efforts for the clinical translation of this approach.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi158-vi158
Author(s):  
Sol Hooy Oh ◽  
Stephen Ahn ◽  
Jae Sung Park ◽  
Yong Kil Hong ◽  
Sin-Soo Jeon

Abstract BACKGROUND Dendritic cell (DC)-based vaccines have been suggested as one of the promising immunotherapies for treating various cancers, including glioblastoma. We already developed a novel vaccination protocol with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine- polycytidylic acid (poly-IC) and anti-CD40 antibodies (Trivax) in a melanoma mouse model. However, in a glioma mouse model, therapeutic efficacy is not as much as enough maybe due to relatively low antigenicity and blood brain barrier. MATERIAL AND METHODS IL-7, which is one of the most important cytokines to expand and develop T cells with anti-tumor immunity, was co-administrated intravenously with Trivax in an orthotopic murine malignant glioma. RESULTS Co-administration of the Trivax and recombinant IL-7 (Trivax7) increased the number of survivin specific T cells measured using ELISPOT assay and the population of central memory T cells, comparing with administration of Trivax. The tumor size of orthotopic mouse model in Trivax 7 group was smaller than those of Trivax only group. Finally, overall survival in Trivax 7 was longer than those of Trivax only. In addition, there was a prolonged survival of antigen-specific T cells in Trivax7 group than Trivax only group. CONCLUSION In summary, our novel combinational immunotherapy may overcome the limitations of current cell-based cancer vaccines and could be applicable for the treatment of glioblastoma patients.


2020 ◽  
Author(s):  
Adarsh Kumbhari ◽  
Colt A. Egelston ◽  
Peter P. Lee ◽  
Peter S. Kim

ABSTRACTTherapeutic vaccines can elicit tumor-specific cytotoxic T lymphocytes (CTLs), but durable reductions in tumor burden require vaccines that stimulate high-avidity CTLs. Recent advances in immunotherapy responses have led to renewed interest in vaccine approaches, including dendritic cell vaccine strategies. However, dendritic cell requirements for vaccines that generate potent anti-tumor T-cell responses are unclear. Here we use mathematical modeling to show that counterintuitively, increasing levels of immature dendritic cells may lead to selective expansion of high-avidity CTLs. This finding contrasts with traditional dendritic cell vaccine approaches that have sought to harness ex vivo generated mature dendritic cells. We show that the injection of vaccine antigens in the context of increased numbers of immature dendritic cells results in a decreased overall peptide:MHC complex load that favors high-avidity CTL activation and expansion. Overall, our results provide a firm basis for further development of this approach, both alone and in combination with other immunotherapies such as checkpoint blockade.


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