A Novel CRAd in Combination With Cisplatin Enhanced the Antitumor Efficacy in Ovarian Cancer

Zhang, Bei; Liu, Yaowu; Zhang, Peiying; Wei, Yaqin; Yin, Xiaoxing; Zheng, Junnian

doi:10.1097/igc.0b013e31823105ed

Cited by 5 publications

(6 citation statements)

References 31 publications

(25 reference statements)

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“…A similar adenoviral agent to ours (CRAd-S-RGD [arginine-lysine-aspartate]) was also investigated in combination with cisplatin for ovarian cancer. Their virus results in synergistically increased efficacy in a xenograft flank tumor model without a concomitant increase in toxicity 43 . The RGD modification on the fiber knob domain of this virus enhances tumor cell infection via integrins instead of the polylysine-facilitated infection in our virus that utilizes proteoglycans.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer

Mooney

Majid

Batalla‐Covello

et al. 2019

Molecular Therapy - Oncolytics

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Oncolytic virotherapy is a promising approach for treating recurrent and/or drug-resistant ovarian cancer. However, its successful application in the clinic has been hampered by rapid immune-mediated clearance or neutralization of the virus, which reduces viral access to tumor foci. To overcome this barrier, patient-derived mesenchymal stem cells have been used to deliver virus to tumors, but variability associated with autologous cell isolations prevents this approach from being broadly clinically applicable. Here, we demonstrate the ability of an allogeneic, clonal neural stem cell (NSC) line (HB1.F3.CD21) to protect oncolytic viral cargo from neutralizing antibodies within patient ascites fluid and to deliver it to tumors within preclinical peritoneal ovarian metastases models. The viral payload used is a conditionally replication-competent adenovirus driven by the survivin promoter (CRAd-S-pk7). Because the protein survivin is highly expressed in ovarian cancer, but not in normal differentiated cells, viral replication should occur selectively in ovarian tumor cells. We found this viral agent was effective against cisplatin-resistant ovarian tumors and could be used as an adjunct treatment with cisplatin to decrease tumor burden without increasing toxicity. Collectively, our data suggest NSC-delivered CRAd-S-pk7 virotherapy holds promise for improving clinical outcome, reducing toxicities, and improving quality of life for patients with advanced ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer

Mooney

Majid

Batalla‐Covello

et al. 2019

Molecular Therapy - Oncolytics

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“…Since RGD is an α v -integrin binding motif, the addition of this peptide allows the adenovirus attachment to different integrins, like α v β 3 orα v β 5 , and subsequently the virus infects the cell in a CAR-independent manner [58] . The ability of this modified fiber to mediate adenovirus infection in CAR-negative cells has been exploited in multiple virotherapy studies for a broad range of tumors as for example in glioma [59] , [60] , [61] , osteosarcoma [62] , [63] , ovarian cancer [64] , prostate cancer [65] or bladder cancer [66] .…”

Section: Oncolytic Adenoviruses As Therapeutic Tools: Widening Adenovmentioning

confidence: 99%

Oncolytic adenoviruses as a therapeutic approach for osteosarcoma: A new hope

García-Moure

Martínez-Vélez

Patiño-García

et al. 2017

Journal of Bone Oncology

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Osteosarcoma is the most common bone cancer among those with non-hematological origin and affects mainly pediatric patients. In the last 50 years, refinements in surgical procedures, as well as the introduction of aggressive neoadjuvant and adjuvant chemotherapeutic cocktails, have increased to nearly 70% the survival rate of these patients. Despite the initial therapeutic progress the fight against osteosarcoma has not substantially improved during the last three decades, and almost 30% of the patients do not respond or recur after the standard treatment. For this group there is an urgent need to implement new therapeutic approaches. Oncolytic adenoviruses are conditionally replicative viruses engineered to selectively replicate in and kill tumor cells, while remaining quiescent in healthy cells. In the last years there have been multiple preclinical and clinical studies using these viruses as therapeutic agents in the treatment of a broad range of cancers, including osteosarcoma. In this review, we summarize some of the most relevant published literature about the use of oncolytic adenoviruses to treat human osteosarcoma tumors in subcutaneous, orthotopic and metastatic mouse models. In conclusion, up to date the preclinical studies with oncolytic adenoviruses have demonstrated that are safe and efficacious against local and metastatic osteosarcoma. Knowledge arising from phase I/II clinical trials with oncolytic adenoviruses in other tumors have shown the potential of viruses to awake the patient´s own immune system generating a response against the tumor. Generating osteosarcoma immune-competent adenoviruses friendly models will allow to better understand this potential. Future clinical trials with oncolytic adenoviruses for osteosarcoma tumors are warranted.

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“…[118][119][120][121] It has been reported that virotherapy combined with chemotherapy is a potential therapeutic modality for the improvement of transfection efficiency and therapeutic efficacy for ovarian cancer. 122,123 Zhang et al demonstrated a synergistic effect in the combination of a novel surviving promoter-based conditionally replicating adenovirus and cisplatin in the enhancement of the antitumor efficacy in ovarian cancer while Franke et al reported that tobacco mosaic virus delivered cisplatin restored efficacy in platinum-resistant ovarian cancer cells. 122,124 In addition, It is reported that some microtubule-disrupting drugs, such as PTX, can improve gene transfection efficiency at a non-cytotoxic dosage.…”

Section: Codelivery Of Viral Gene and Anticancer Drugmentioning

confidence: 99%

Nanoparticle-Based Combination Therapy for Ovarian Cancer

Wu¹,

Yang²,

Lv³

et al. 2023

IJN

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Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.

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A Novel CRAd in Combination With Cisplatin Enhanced the Antitumor Efficacy in Ovarian Cancer

Cited by 5 publications

References 31 publications

Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer

Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer

Oncolytic adenoviruses as a therapeutic approach for osteosarcoma: A new hope

Nanoparticle-Based Combination Therapy for Ovarian Cancer

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