Overexpressed oncogenic tumor-self antigens

Bright, Robert K.; Bright, Jennifer D.; Byrne, Jennifer A.

doi:10.4161/hv.29475

Cited by 54 publications

(52 citation statements)

References 93 publications

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“…The overexpressed self-antigens, as the name indicates, are overexpressed in tumors, while their presence is low but detectable in normal cells. These antigens induce immune responses only against cancerous cells and leave normal ones unharmed, in other words, they do not provoke autoimmunity [35] [36].…”

Section: Discussionmentioning

confidence: 99%

Designing a novel multi-epitope T vaccine for “targeting protein for Xklp-2” (TPX2) in hepatocellular carcinoma based on immunoinformatics approach

Ghahremanifard

Afzali

Rostami

et al. 2019

Preprint

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Hepatocellular carcinoma (HCC) is one of the leading cancer-related deaths worldwide.Recently, studies for HCC treatment are focused on cancer immunotherapy, particularly cancer vaccines, to complete and assist other therapies. TPX2 is a microtubule-associated protein necessary for cell division; therefore, alteration in its expression, especially up regulation, is associated with several human carcinomas such as HCC.In this study, immunoinformatics tools were used to design a rational multi-epitope T vaccine against TPX2 in HCC. Cytotoxic T lymphocytes (CTL) and Helper T lymphocytes (HTL) epitopes were predicted and Maltose-binding protein (MBP) was added to the construct as an adjuvant. Evaluation of vaccine properties was indicated that our construct is stable and immunogenic enough to induce relevant responses besides not being allergic. After predicting the tertiary structure and energy minimization, protein-protein docking was performed to calculate the free energy of possible interactions between the vaccine and tolllike receptor 4 (TLR4) to assure that simultaneous complementary responses would be activated by our construct. Finally, Codon optimization and in-silico cloning were performed to ensure the vaccine expression efficiency in the desired host.

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Section: Discussionmentioning

confidence: 99%

Designing a novel multi-epitope T vaccine for “targeting protein for Xklp-2” (TPX2) in hepatocellular carcinoma based on immunoinformatics approach

Ghahremanifard

Afzali

Rostami

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Since the first immunogenic antigen MAGE-1 was brought to light, several immunogenic antigens have been reported 36 , 37 . But majority of them is shared TAAs that are expressed by both tumor cells and normal cells, despite the fact that, at a relative lower level, the on-target/off tumor effects pose to be potential threats 38 , 39 . Furthermore, shared TAAs can be classified into three groups: 1) cancer-testis antigens; 2) tissue differentiation antigens; and 3) over-expressed antigens (table.…”

Section: Obstacles Limiting Cancer Vaccinesmentioning

confidence: 99%

“…Through the discovery of this mechanism, there have been developed numerous for the purpose of targeting those immune checkpoints, such as PD-1 inhibitors, Nivolumab and Pembrolizumab that have been both appraised and approved by the FDA in respect of the treatment of melanoma, non-small cell lung cancer (NSCLC) and melanoma respectively 50 . Furthermore, the therapeutic efficiency of PD-1 inhibitors was reported having association with the somatic mutation load, which is coupled with the dysfunction of MMR system 38 . It implies that the higher somatic mutation load of the patients together with the higher number of neo-antigens will be encoded, and the higher response rate of the patients will be attained from PD-1 inhibitors 56 .…”

Section: Lessons Learned From Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Cancer vaccine: learning lessons from immune checkpoint inhibitors

Qian

Jin

et al. 2018

J. Cancer

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Cancer vaccines have been exclusively studied all through the past decades, and have made exceptional achievements in cancer treatment. Few cancer vaccines have been approved by the US Food and Drug Administration (FDA), for instance, Provenge, which was approved for the treatment of prostate carcinoma in 2012. Moreover, more recently, T-VEC got approval for the treatment of melanoma. While, the overall therapeutic effects of cancer vaccines have been taken into consideration as below expectations, low antigenicity of targeting antigen and tumor heterogeneity are the two key limiting barriers encountered by the cancer vaccines. Nonetheless, recent developments in cancer immune-therapies together with associated technologies, for instance the unparalleled achievements bagged by immune checkpoint inhibitor based therapies and neo-antigen identification tools, envisage potential improvements in cancer vaccines in respect to the treatments of malignancies. This review brings forth measures for the purpose of refining therapeutic cancer vaccines by learning lessons from the success of PD-1 inhibitor based immune-therapies.

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“…The mechanism of AEs may be that specific antigen encoded by prostate acid phosphatase fusion protein, selectively induced to specific immune response to cancer cells, has expression in the normal cells but peptide epitope is not high enough, resulting in weak immune response. 36 The combination of antigen specific cancer vaccine and checkpoint inhibitors do not appear to lead to increased toxicity.…”

Section: The Toxicities Of Cancer Vaccinesmentioning

confidence: 99%

Recognizing and managing on toxicities in cancer immunotherapy

et al. 2017

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Over the past 4 years, cancer immunotherapy has significantly prolonged survival time of patients with prostate cancer, melanoma, lung cancer, and liver cancer, but its side effects are also impressive. Different types of the immune therapeutic agents have different on-target or off-target toxicity due to high affinity or weak specificity, respectively. Treatment toxicity spectrums vary greatly even in patients with the same type of cancer. Common toxicities are fevers, chills, diarrhea colitis, maculopapular rash, hepatitis, and hormone gland disorder; therefore, routine monitoring of thyroid function, liver function, renal function, and complete blood count are absolutely necessary once treatment begins. Some side effects are reversible, and can be processed through the standard medicines. However, serious toxicities are lethal, which should be frequently followed-up, identified at an early stage and immediately symptomatic treated by high-dose immunosuppressors. In this case, thereafter, the same agent should not be challenged again.

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Overexpressed oncogenic tumor-self antigens

Cited by 54 publications

References 93 publications

Designing a novel multi-epitope T vaccine for “targeting protein for Xklp-2” (TPX2) in hepatocellular carcinoma based on immunoinformatics approach

Designing a novel multi-epitope T vaccine for “targeting protein for Xklp-2” (TPX2) in hepatocellular carcinoma based on immunoinformatics approach

Cancer vaccine: learning lessons from immune checkpoint inhibitors

Recognizing and managing on toxicities in cancer immunotherapy

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