Delivery of mRNA vaccines and anti-PDL1 siRNA through non-invasive transcutaneous route effectively inhibits tumor growth

10061 Background: Although a number of advances in ovarian cancer treatment have occurred in the last decade, most patients will experience a recurrence after standard therapies. Recently, virotherapy has been proposed as a new therapeutic approach for ovarian cancer. Conditionally replicative adenovirus (CRAd) contains tumor-specific promoters that restrict virus replication to cancer cells and has shown particular promise as oncolytic viral agents. However, the lack of a tumor-volume monitoring system hinders the evaluation of CRAd impact on cancer treatment. Therefore, methods for analyzing CRAd efficacy and tumor response are required. Mesothelin, a cell surface glycoprotein, is overexpressed in ovarian cancer but not in normal ovarian tissues. The purpose of this study was to explore the therapeutic utility of a mesothelin promoter-based CRAd in a murine model of ovarian cancer, using a non-invasive biological imaging system. Methods: We constructed a mesothelin promoter based CRAd which also contains a modified fiber (Ad5/3 fiber) previously shown to improve infectivity of many ovarian cancer cells (Ad5/3MSLN). Viral replication and oncolysis were assessed in a panel of ovarian cancer cell lines. To test the oncolytic efficacy of Ad5/3MSLN in murine model, firefly luciferase-expressing SK-OV-3-luc cells were injected intraperitoneally (i.p.), followed by an i.p. injection of viruses. Then, bioluminescence imaging of tumor luciferase activity was carried out. Results: Ad5/3MSLN achieved up to 10,000-fold higher cell killing effect and up to 120-fold higher levels of viral replication in all ovarian cancer cell lines tested, compared to wild type Ad5. In vivo tumor imaging confirmed that Ad5/3MSLN significantly inhibited tumor growth, while the untreated mice had rapid tumor growth (p<0.05). Survival with Ad5/3MSLN was significantly enhanced when compared with no virus, or wild type Ad5-treated group (p<0.05). Conclusions: The robust replication, oncolysis, and in vivo therapeutic efficacy of Ad5/3MSLN demonstrated that this CRAd is a promising candidate for treating ovarian cancer. Importantly, we have established an in vivo non-invasive imaging system, which has allowed repeated and longitudinal measurements of tumor growth after CRAd treatment. No significant financial relationships to disclose.

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Non-invasive monitoring of patient-derived orthotopic xenograft: An optimal system for rapid in vivotesting.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.235 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 235-235

Author(s):

Mayrim V. Rios Perez ◽

Michael Pratt ◽

Ya'an Kang ◽

Jason B. Fleming

Keyword(s):

Tumor Growth ◽

Mouse Models ◽

Response To Therapy ◽

Ductal Adenocarcinoma ◽

In Vivo Models ◽

Treatment Groups ◽

Non Invasive ◽

Orthotopic Xenograft ◽

Metastatic Burden

235 Background: Heterotopic patient-derived xenografts (PDX) have been used to assess response to therapy however they underrepresent the role of tumor microenvironment and rarely develop metastasis, both of which are overcome by orthotopic models. Fluorescent orthotopic mouse models require invasive measures to determine tumor bioluminescence. Ultrasonography (US) is a cost-effective, non-invasive imaging technique that has been used in genetically engineered mouse models of pancreatic cancer for a three-dimensional (3D) acquisition of tumor volume, which allows rapid and safe in vivo drug testing. We intend to demonstrate that this technique allows real time monitoring of in vivo response to therapy using patient-derived orthotopic xenograft (PDOX) of pancreatic ductal adenocarcinoma (PDAC). Methods: A non-survival study using PDOX was designed with control (n = 5) and treatment (n = 5) groups. Weekly 3D US images were obtained pre and post-treatment over 4 weeks. Tumor growth curves were generated to monitor progression of disease. Metastatic burden was determined during necropsy. Results: One mouse was excluded from control and treatment groups due to baseline tumor size exceeding 300mm3 and drug toxicity, respectively. Pre-treatment average tumor volumes for control and treatment groups were (36±12)mm3 and (34±12)mm3, respectively. No difference was found in average tumor growth over time between groups (p = 0.9120). A 20% tumor regression was observed per group. Both groups exhibited gross metastasis to spleen, peritoneum, and omentum. Liver, periportal metastasis and local extension to the gastrointestinal and genitourinary system were present on the treatment group. Conclusions: This study describes a rapid technique for in vivo drug response by using 3D US to monitor PDOX; failure of response to therapy correlated with metastatic burden observed. PDOX regression could be explained by tumor heterogeneity. PDOX models, as challenging as they could be, remain to be necessary in vivo models to show therapeutic response to human PDAC, which could be easily monitored using 3D US imaging.

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Non-Invasive Markers of Tumor Growth, Metastases and Sensitivity to AntiNeoplastic Therapy

10.21236/ada460278 ◽

2006 ◽

Author(s):

Jason A. Koutcher

Keyword(s):

Tumor Growth ◽

Antineoplastic Therapy ◽

Non Invasive

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The role of the microenvironment in regulation of CSPG-driven invasive and non-invasive tumor growth in glioblastoma

Japan Journal of Industrial and Applied Mathematics ◽

10.1007/s13160-015-0188-2 ◽

2015 ◽

Vol 32 (3) ◽

pp. 771-805 ◽

Cited By ~ 2

Author(s):

Hyun Geun Lee ◽

Yangjin Kim

Keyword(s):

Tumor Growth ◽

Invasive Tumor ◽

Non Invasive

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Non-invasive prediction of the tumor growth rate using advanced diffusion models in head and neck squamous cell carcinoma patients

Oncotarget ◽

10.18632/oncotarget.16851 ◽

2017 ◽

Vol 8 (20) ◽

pp. 33631-33643 ◽

Cited By ~ 1

Author(s):

Noriyuki Fujima ◽

Tomohiro Sakashita ◽

Akihiro Homma ◽

Taisuke Harada ◽

Yukie Shimizu ◽

...

Keyword(s):

Growth Rate ◽

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Diffusion Models ◽

Neck Squamous Cell Carcinoma ◽

Tumor Growth Rate ◽

Non Invasive

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In-vivo monitoring and quantification of breast cancer growth dynamics with non-invasive intravital mesoscopic fluorescence molecular tomography

10.1101/2020.08.03.234898 ◽

2020 ◽

Author(s):

Mehmet S. Ozturk ◽

Marta G. Montero ◽

Ling Wang ◽

Lucas M. Chaible ◽

Martin Jechlinger ◽

...

Keyword(s):

Tumor Growth ◽

Tumor Cells ◽

Tumor Volume ◽

Residual Disease ◽

Growth Dynamics ◽

Treatment Phase ◽

High Sensitivity ◽

Fluorescence Molecular Tomography ◽

Non Invasive

Preclinical breast tumor models are an invaluable tool to systematically study tumor progression and treatment response, yet methods to non-invasively monitor the involved molecular and mechanistic properties under physiologically relevant conditions are limited. Here we present an intravital mesoscopic fluorescence molecular tomography (henceforth IFT) approach that is capable of tracking fluorescently labeled tumor cells in a quantitative manner inside the mammary gland of living mice. Our mesoscopic approach is entirely non-invasive and thus permits prolonged observational periods of several months. The relatively high sensitivity and spatial resolution further enable inferring the overall number of oncogene-expressing tumor cells as well as their tumor volume over the entire cycle from early tumor growth to residual disease following the treatment phase. We find that sheer tumor volume, as commonly assessed by other imaging modalities, is not well correlated to tumor cell quantity, hence our IFT approach is a promising new method for studying tumor growth dynamics in a quantitative and longitudinal fashion in-vivo.

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