scholarly journals A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5801
Author(s):  
Alexandre Harari ◽  
Apostolos Sarivalasis ◽  
Kaat de Jonge ◽  
Anne-Christine Thierry ◽  
Florian Huber ◽  
...  

Endometrial cancer (EC) is a common gynecological malignancy and the fourth most common malignancy in European and North American women. Amongst EC, the advanced serous, p53-mutated, and pMMR subtypes have the highest risk of relapse despite optimal standard of care therapy. At present, there is no standard of care maintenance treatment to prevent relapse among these high-risk patients. Vaccines are a form of immunotherapy that can potentially increase the immunogenicity of pMMR, serous, and p53-mutated tumors to render them responsive to check point inhibitor-based immunotherapy. We demonstrate, for the first time, the feasibility of generating a personalized dendritic cell vaccine pulsed with peptide neoantigens in a patient with pMMR, p53-mutated, and serous endometrial adenocarcinoma (SEC). The personalized vaccine was administered in combination with systemic chemotherapy to treat an inoperable metastatic recurrence. This treatment association demonstrated the safety and immunogenicity of the personalized dendritic cell vaccine. Interestingly, a complete oncological response was obtained with respect to both radiological assessment and the tumor marker CA-125.

2011 ◽  
Vol 71 (21) ◽  
pp. 6611-6620 ◽  
Author(s):  
Huanfa Yi ◽  
Chunqing Guo ◽  
Xiaofei Yu ◽  
Ping Gao ◽  
Jie Qian ◽  
...  

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.


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.


2009 ◽  
Vol 29 (3) ◽  
pp. 265-270
Author(s):  
Dan-feng XU ◽  
Yi GAO ◽  
Yu-shan LIU ◽  
Xin-gang CUI ◽  
Jian-ping CHE ◽  
...  

2015 ◽  
Vol 23 ◽  
pp. S167
Author(s):  
Hiroki Saito ◽  
Koichi Kitagawa ◽  
Risa Yamasaki ◽  
Nami Katai ◽  
Naoya Morishita ◽  
...  

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