Development of inCVAX, In situ Cancer Vaccine, and Its Immune Response in Mice with Hepatocellular Cancer

Qi, Xiaoqiang; Lam, Samuel Siu Kit; Dai, Li‐Xin; Kim, Dae Young; Ma, Lixin; Alleruzzo, Lu; Chen, Wei; Hode, Tomas; Henry, Carolyn J.; Kaifi, Jussuf T.; Kimchi, Eric T.; Li, Guangfu; Staveley-O’Carroll, Kevin F.

doi:10.4172/2155-9899.1000438

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…Human Panc-1 and MIA PaCa-2 cells were purchased from ATCC (Manassas, VA, United States). The cell lines were maintained in Dulbecco’s Modified Eagle Medium (DMEM; Cellgro, Manassas, VA, United States) supplemented with 100 U/mL penicillin, 100 μg/mL streptomycin, 2 mmol/L L-glutamine, 10 mmol/L HEPES, and 10% fetal bovine serum (FBS) at 37°C in a 5% CO 2 humidified atmosphere ( Qi et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis

Liu

Hao

Zhou

et al. 2021

Front. Cell Dev. Biol.

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Pancreatic cancer (PC) is one of the most lethal human malignancies without effective treatment. In an effort to discover key genes and molecular pathways underlying PC growth, we have identified LIM domain only 7 (LMO7) as an under-investigated molecule, which highly expresses in primary and metastatic human and mouse PC with the potential of impacting PC tumorigenesis and metastasis. Using genetic methods with siRNA, shRNA, and CRISPR-Cas9, we have successfully generated stable mouse PC cells with LMO7 knockdown or knockout. Using these cells with loss of LMO7 function, we have demonstrated that intrinsic LMO7 defect significantly suppresses PC cell proliferation, anchorage-free colony formation, and mobility in vitro and slows orthotopic PC tumor growth and metastasis in vivo. Mechanistic studies demonstrated that loss of LMO7 function causes PC cell-cycle arrest and apoptosis. These data indicate that LMO7 functions as an independent and unrecognized druggable factor significantly impacting PC growth and metastasis, which could be harnessed for developing a new targeted therapy for PC.

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Section: Methodsmentioning

confidence: 99%

LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis

Liu

Hao

Zhou

et al. 2021

Front. Cell Dev. Biol.

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“…Specimens, including the wounded skin and liver, were immediately fixed in 10% of formalin for 2 days. The fixed tissues were embedded in paraffin, sectioned at 5 μm thickness, and stained with hematoxylin and eosin [39]. Three sections of each tissue were evaluated and scored by a veterinary pathologist unaware of the treatment conditions.…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial efficacy and toxicity of novel CAMPs against P. aeruginosa infection in a murine skin wound infection model

et al. 2019

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BackgroundTreatment of P. aeruginosa wound infection is challenging due to its inherent and acquired resistance to many conventional antibiotics. Cationic antimicrobial peptides (CAMPs) with distinct modes of antimicrobial action have been considered as the next-generation therapeutic agents. In the present study, a murine skin surgical wound infection model was used to evaluate the in vivo toxicity and efficacy of two newly designed antimicrobial peptides (CAMP-A and CAMP-B), as chemotherapeutic agents to combat P. aeruginosa infection.ResultsIn the first trial, topical application of CAMPs on the wounds at a dose equivalent to 4 × MIC for 7 consecutive days did not cause any significant changes in the physical activities, hematologic and plasma biochemical parameters, or histology of systemic organs of the treated mice. Daily treatment of infected wounds with CAMP-A and CAMP-B for 5 days at a dose equivalent to 2× MIC resulted in a significant reduction in wound bacterial burden (CAMP-A: 4.3 log10CFU/g of tissue and CAMP-B: 5.8 log10CFU/g of tissue), compared to that of the mock-treated group (8.1 log10CFU/g of tissue). Treatment with CAMPs significantly promoted wound closure and induced epidermal cell proliferation. Topical application of CAMP-A on wounds completely prevented systemic dissemination of P. aeruginosa while CAMP-B blocked systemic infection in 67% of mice and delayed the onset of systemic infection by at least 2 days in the rest of the mice (33%). In a second trial, daily application of CAMP-A at higher doses (5× MIC and 50× MIC) didn’t show any significant toxic effect on mice and the treatments with CAMP-A further reduced wound bacterial burden (5× MIC: 4.5 log10CFU/g of tissue and 50× MIC: 3.8 log10CFU/g of tissue).ConclusionsThe data collectively indicated that CAMPs significantly reduced wound bacterial load, promoted wound healing, and prevented hepatic dissemination. CAMP-A is a promising alternative to commonly used antibiotics to treat P. aeruginosa skin infection.

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“…Recently the development of an in situ cancer vaccine InCVAX for the treatment of HCC has been reported [ 74 , 75 ]. InCVAX works by stimulating robust antitumor immune reactions via a two-pronged approach.…”

Section: Immunotherapeutic Approaches To Treat Liver Cancermentioning

confidence: 99%

“…This includes a thermal treatment of tumors, such as with a laser, followed by administration of N -dihydro-galacto-chitosan (NDGC). Thermal treatment releases antigens and increases immunogenicity, while NDGC acts as a potent immune activator [ 74 ]. In that study, the strategy of local immunological cell death with DC activation with NDGC was found to be effective in a murine HCC model.…”

Section: Immunotherapeutic Approaches To Treat Liver Cancermentioning

confidence: 99%

“…In that study, the strategy of local immunological cell death with DC activation with NDGC was found to be effective in a murine HCC model. Tumor infiltration of CD3 + , CD4 + , and CD8 + cells was observed after the injection of InCVAX, which indicated the in situ elimination of the tumor [ 74 ]. A vaccine containing the epitope of α-fetoprotein (AFP) linked with a heat shock protein 70 epitope also elicited anti-tumoral immunity by activating AFP-specific CD8 + T cells and was effective in reducing tumors in mice [ 76 ].…”

Section: Immunotherapeutic Approaches To Treat Liver Cancermentioning

confidence: 99%

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Immune-Mediated Therapies for Liver Cancer

Aravalli

Steer

2017

Genes

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In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma.

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Development of inCVAX, In situ Cancer Vaccine, and Its Immune Response in Mice with Hepatocellular Cancer

Cited by 16 publications

References 31 publications

LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis

LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis

Antimicrobial efficacy and toxicity of novel CAMPs against P. aeruginosa infection in a murine skin wound infection model

Immune-Mediated Therapies for Liver Cancer

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