scholarly journals Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 627
Author(s):  
Courtney T. Stump ◽  
Gregory Ho ◽  
Chenkai Mao ◽  
Frank A. Veliz ◽  
Veronique Beiss ◽  
...  

Ovarian cancer is the deadliest gynecological malignancy. Though most patients enter remission following initial interventions, relapse is common and often fatal. Accordingly, there is a substantial need for ovarian cancer therapies that prevent relapse. Following remission generated by surgical debulking and chemotherapy, but prior to relapse, resected and inactivated tumor tissue could be used as a personalized vaccine antigen source. The patient’s own tumor contains relevant antigens and, when combined with the appropriate adjuvant, could generate systemic antitumor immunity to prevent relapse. Here, we model this process in mice to investigate the optimal tumor preparation and vaccine adjuvant. Cowpea mosaic virus (CPMV) has shown remarkable efficacy as an immunostimulatory cancer therapy in ovarian cancer mouse models, so we use CPMV as an adjuvant in a prophylactic vaccine against a murine ovarian cancer model. Compared to its codelivery with tumor antigens prepared in three other ways, we show that CPMV co-delivered with irradiated ovarian cancer cells constitutes an effective prophylactic vaccine against a syngeneic model of ovarian cancer in C57BL/6J mice. Following two vaccinations, 72% of vaccinated mice reject tumor challenges, and all those mice survived subsequent rechallenges, demonstrating immunologic memory formation. This study supports remission-stage vaccines using irradiated patient tumor tissue as a promising option for treating ovarian cancer, and validates CPMV as an antitumor vaccine adjuvant for that purpose.

2019 ◽  
Vol 7 (18) ◽  
pp. 2938-2947 ◽  
Author(s):  
Jing Wang ◽  
Yonghong Song ◽  
Mingxun Zhang ◽  
Zhensheng Wu ◽  
Yun-Jun Xu ◽  
...  

A liposomal curcumol nanocomposite has been successfully synthesized for the theranostics of human primary ovarian cancer cells from solid tumor tissue in patients.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Leonardo Mirandola ◽  
Maurizio Chiriva-Internati ◽  
Robert Bresalier ◽  
Lucia Piccotti ◽  
Fabio Grizzi ◽  
...  

Abstract Background The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and presented in the right context. Methods We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients. Results We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3+ T-reg cells in vitro. Conclusions This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients.


2018 ◽  
Vol 5 (5) ◽  
pp. 1700991 ◽  
Author(s):  
Anna E. Czapar ◽  
Brylee David B. Tiu ◽  
Frank A. Veliz ◽  
Jonathan K. Pokorski ◽  
Nicole F. Steinmetz

2019 ◽  
Vol 154 ◽  
pp. 93-94
Author(s):  
C. Dominick ◽  
P. Joseph ◽  
E. Ponting ◽  
A.J. Armstrong ◽  
J. Nakayama ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 46120-46126 ◽  
Author(s):  
Kamila Kloudová ◽  
Hana Hromádková ◽  
Simona Partlová ◽  
Tomáš Brtnický ◽  
Lukáš Rob ◽  
...  

2017 ◽  
Vol 27 (9) ◽  
pp. 2000-2005 ◽  
Author(s):  
Rajarshi Kar ◽  
Diwesh Chawla ◽  
Bindiya Gupta ◽  
Mohit Mehndiratta ◽  
Neelam Wadhwa ◽  
...  

ObjectiveOvarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol.MethodsComplete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media.ResultsPrimary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages.ConclusionThis study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.


Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 44 ◽  
Author(s):  
Afsar Rahbar ◽  
Amira AlKharusi ◽  
Helena Costa ◽  
Mattia Russel Pantalone ◽  
Ourania N. Kostopoulou ◽  
...  

One of the potential biomarkers for ovarian cancer patients is high serum level of prolactin (PRL), which is a growth factor that may promote tumor cell growth. The prolactin receptor (PRLR) and human cytomegalovirus (HCMV) proteins are frequently detected in ovarian tumor tissue specimens, but the potential impact of HCMV infection on the PRL system have so far not been investigated. In this study, HCMV’s effects on PRL and PRLR expression were assessed in infected ovarian cancer cells (SKOV3) by PCR and Western blot techniques. The levels of both PRL and PRLR transcripts as well as the corresponding proteins were highly increased in HCMV-infected SKOV3 cells. Tissue specimens obtained from 10 patients with ovarian cancer demonstrated high expression of PRLR, HCMV-IE, and pp65 proteins. Extensive expression of PRLR was detected in all examined ovarian tumor tissue specimens except for one from a patient who had focal expression of PRLR and this patient was HCMV-negative in her tumor. In conclusion, PRL and PRLR were induced to high levels in HCMV-infected ovarian cancer cells and PRLR expression was extensively detected in HCMV-infected ovarian tissue specimens. Highly induced PRL and PRLR by HCMV infection may be of relevance for the oncomodulatory role of this virus in ovarian cancer.


2017 ◽  
Vol 15 (8) ◽  
pp. 2922-2931 ◽  
Author(s):  
Christina E. Franke ◽  
Anna E. Czapar ◽  
Ravi B. Patel ◽  
Nicole F. Steinmetz

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  

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