Immunological and Clinical Effects of Vaccines Targeting p53‐Overexpressing Malignancies

Vermeij, Renee; Leffers, Ninke; Burg, Sjoerd H. van der; Melief, Cornelis J.M.; Daemen, Toos; Nijman, Hans W.

doi:10.1155/2011/702146

Cited by 41 publications

(36 citation statements)

References 94 publications

(89 reference statements)

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“…There is an increasing attention to develop different strategies that can modulate p53-dependent apoptotic pathways such as inhibition of p53-MDM2 interaction using MDM2 inhibitors, restoring mutated p53 back to its wild-type form and p53 vaccines [158][159][160].…”

Section: Death Receptormentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.

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Section: Death Receptormentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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“…In addition, numerous clinical trials have been performed using different kinds of p53 vaccines including I) short and long peptide-based vaccines, II) dendritic cellbased vaccines, and III) recombinant replication-defective adenoviral vectors with human wild-type p53 (Kuball et al, 2002;Svane et al, 2004;Vermeij et al, 2011).…”

Section: Targeting P53mentioning

confidence: 99%

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

490

338

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Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

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“…Historically, especially within the first 20 years of p53 research, the connection of p53 with host immune response and regulation had been mostly limited to employing fragments of p53 protein as tumor-associated antigens (TAAs) for tumor vaccines [20,21,22] because many forms of p53 mutation stabilize the p53 protein, resulting in elevated p53 level in tumors [1,3,23,24]. Recently, our studies and those of others have shown that p53 inactivation/dysfunction alters the immune landscape of the tumor microenvironment (TME) towards pro-tumor inflammation [25,26,27,28], whereas p53 reactivation or restoration changes the milieu of TME to promote antitumor immunity [29,30,31].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment

Cui

Guo

2016

IJMS

105

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The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME). It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome.

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Immunological and Clinical Effects of Vaccines Targeting p53‐Overexpressing Malignancies

Cited by 41 publications

References 94 publications

Major apoptotic mechanisms and genes involved in apoptosis

Major apoptotic mechanisms and genes involved in apoptosis

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment

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