The Promise of Preventive Cancer Vaccines

Lollini, Pier‐Luigi; Cavallo, Federica; Nanni, Patrizia

doi:10.3390/vaccines3020467

Cited by 35 publications

(27 citation statements)

References 129 publications

(152 reference statements)

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“…Cancer vaccines are generated using different approaches. They are accomplished by exposure to cancer cells, cell lysates, RNA/DNA, or engineered-viral tumour antigens, but most commonly developed through tumour-associated antigens (TAA) [7,8]. These vaccines can be used for prevention-such as the FDA-approved hepatitis B virus (HBV) vaccine for liver cancer and human papillomavirus (HPV) vaccine for cervical cancer [9,10]-or therapeutically to regulate the progression of existing tumours.…”

Section: Cancer Vaccinesmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Law

Valdés-Mora

Gallego‐Ortega

2020

Cells

334

272

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The emergence of immunotherapy has been an astounding breakthrough in cancer treatments. In particular, immune checkpoint inhibitors, targeting PD-1 and CTLA-4, have shown remarkable therapeutic outcomes. However, response rates from immunotherapy have been reported to be varied, with some having pronounced success and others with minimal to no clinical benefit. An important aspect associated with this discrepancy in patient response is the immune-suppressive effects elicited by the tumour microenvironment (TME). Immune suppression plays a pivotal role in regulating cancer progression, metastasis, and reducing immunotherapy success. Most notably, myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have potent mechanisms to inhibit T-cell and NK-cell activity to promote tumour growth, development of the pre-metastatic niche, and contribute to resistance to immunotherapy. Accumulating research indicates that MDSC can be a therapeutic target to alleviate their pro-tumourigenic functions and immunosuppressive activities to bolster the efficacy of checkpoint inhibitors. In this review, we provide an overview of the general immunotherapeutic approaches and discuss the characterisation, expansion, and activities of MDSCs with the current treatments used to target them either as a single therapeutic target or synergistically in combination with immunotherapy.

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Section: Cancer Vaccinesmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Law

Valdés-Mora

Gallego‐Ortega

2020

Cells

334

272

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“…It is administered prior to cancer development for the purposes of primary prevention. 16,22 Confirmatory studies with further molecular biology techniques are needed to establish a potential role of HER2 in the carcinogenesis of feline mammary tumors. Furthermore, in vitro models could properly establish a possible therapeutic predictivity in the feline species.…”

Section: Discussionmentioning

confidence: 99%

HER2Amplification Status in Feline Mammary Carcinoma: A Tissue Microarray–Fluorescence In Situ Hydridization–Based Study

Muscatello

Oto²,

Sarli

et al. 2018

Vet Pathol

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Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor overexpressed in a subset of breast cancer due to HER2 gene amplification. HER2 protein is expressed in feline mammary carcinomas, but little is known about its cytogenetic alterations. The aim of this study was to evaluate HER2 gene amplification status and its correlation with HER2 protein expression in feline mammary carcinomas. Feline mammary carcinomas were retrospectively selected and immunohistochemically (IHC) evaluated for HER2 protein expression. All the HER2 IHC-positive (3+) and equivocal (2+) cases and a subset of negative cases (0/1+) were selected for fluorescence in situ hybridization (FISH). Dual-core tissue microarrays were prepared for FISH. IHC and FISH were evaluated according to the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The study included 107 feline mammary carcinomas from 88 queens. HER2 protein expression was positive (3+) in 7 cases (6.5%), equivocal (2+) in 48 cases (45%), and negative (0/1+) in 52 cases (48.5%). HER2 status was indeterminate in 8 feline mammary carcinomas (12%), amplified in 3 (4%), equivocal in 4 (6%), and nonamplified in 53 (78%). HER2 gene amplification and protein expression were significantly positively correlated ( R = 0.283; P < .0001). HER2 gene is amplified in a subset of feline mammary carcinomas despite the HER2 positive or equivocal protein expression, but it remains to be determined if the HER2 amplification is a gene alteration that drives mammary tumor carcinogenesis or only a bystander passenger mutation.

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“…Among the vaccination strategies used until now, gene-based vaccines have been shown to possess a number of advantages compared to cell-and protein/peptide-based vaccines, being a relatively simple and very flexible way of activating the immune response in animal models against a specific antigen [53][54][55]. However, simple naked plasmid DNA injection is accompanied by limited uptake and a consequent inadequate antigen transcription by transfected cells [56], and this is particularly evident when naked DNA vaccines are scaled up from smaller species such as mice and rats to non-human primates and humans [57,58]. This issue can be overcome through the use of the in vivo intramuscular electroporation of DNA plasmids (electrovaccination) that has been one of the most effective strategies among the innovative delivery methods exploited until now [59][60][61][62].…”

Section: Of 23mentioning

confidence: 99%

Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

et al. 2020

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Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed with oncoantigen features, is activated by chromosomal rearrangement or overexpression in NSCLC and in several tumor histotypes. In this work, we have exploited transgenic mice harboring the activated K-Ras oncogene (K-RasG12D) that spontaneously develop metastatic NSCLC as a preclinical model to test the efficacy of ROS1 immune targeting. Indeed, qPCR and immunohistochemical analyses revealed ROS1 overexpression in the autochthonous primary tumors and extrathoracic metastases developed by K-RasG12D mice and in a derived transplantable cell line. As proof of concept, we have evaluated the effects of the intramuscular electroporation (electrovaccination) of plasmids coding for mouse- and human-ROS1 on the progression of these NSCLC models. A significant increase in survival was observed in ROS1-electrovaccinated mice challenged with the transplantable cell line. It is worth noting that tumors were completely rejected, and immune memory was achieved, albeit only in a few mice. Most importantly, ROS1 electrovaccination was also found to be effective in slowing the development of autochthonous NSCLC in K-RasG12D mice.

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The Promise of Preventive Cancer Vaccines

Cited by 35 publications

References 129 publications

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

HER2Amplification Status in Feline Mammary Carcinoma: A Tissue Microarray–Fluorescence In Situ Hydridization–Based Study

Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

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