Achilles Heel of Cancer

Pak, Vladimir

doi:10.19080/ctoij.2017.03.555625

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…Targeting MDSCs is a new approach to immunotherapy that can eliminate immune tolerance molecules, activate NK cells, activate T cells and engage the immune system in recognizing and destroying cancer cells through a positive response ( Makkouk and Weiner, 2015 ; Pak, 2017 ). Many lines of evidence have indicated that AFP inhibits the immune response in patients with cancers ( Um et al, 2004 ; Meng et al, 2016 ; Suryatenggara et al, 2017 ; Wang and Wang, 2018 ; Zheng et al, 2020 ).…”

Section: Application Of Aif To Enhance Immunotherapy Of Cancermentioning

confidence: 99%

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

Lin

Wang

et al. 2021

Front. Cell Dev. Biol.

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Alpha fetoprotein (AFP) plays a key role in stimulating the growth, metastasis and drug resistance of hepatocellular carcinoma (HCC). AFP is an important target molecule in the treatment of HCC. The application of AFP-derived peptides, AFP fragments and recombinant AFP (AFP-inhibiting fragments, AIFs) to inhibit the binding of AFP to intracellular proteins or its receptors is the basis of a new strategy for the treatment of HCC and other cancers. In addition, AIFs can be combined with drugs and delivery agents to target treatments to cancer. AIFs conjugated to anticancer drugs not only destroy cancer cells with these drugs but also activate immune cells to kill cancer cells. Furthermore, AIF delivery of drugs relieves immunosuppression and enhances chemotherapy effects. The synergism of immunotherapy and targeted chemotherapy is expected to play an important role in enhancing the treatment effect of patients with cancer. AIF delivery of drugs will be an available strategy for the targeted treatment of cancer in the future.

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Section: Application Of Aif To Enhance Immunotherapy Of Cancermentioning

confidence: 99%

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

Lin

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Accumulation of MDSC and AFP (native or cancer cells-origin) in cancer cells microenvironment makes immune system tolerable to cancer. That is why MDSC is a perfect target for immunotherapy [19,20] and AFP-AFPR delivery system utilization by cancer cells is its "Achilles heel" [21]. MDSC depletion breaks immune tolerance to cancer and became a new generation of immunotherapy that unleashes combined T-cells and NK attack to cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Cancer Is the Innate Immunity Fault

Pak¹

2017

CTOIJ

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While a large portion of cancer immunotherapy's focus on targeting T cells, there has been a surge of interest in harnessing the relatively underexplored NK system for therapeutic intervention. Unlike adaptive immunity innate one starts working immediately with low number of cells and can become the new generation of cancer prophylactic and ordinary immunotherapy. Innate immunity is locally blocked in the cases of embryo cells and cancer stem cells or metastases due to mechanisms that are triggered in the immune system by these types of cells.If you can look into the seeds of time, And say which grain will grow and which will not, Than speak to me. W. ShakespeareOne of the triggers is AFPR that is expressed by embryo cells and re-expressed by the majority of cancer cells. AFPR binds its ligand-AFP loaded with the nutrients. AFP shuttles nutrients from microenvironment to AFPR-positive cells. In addition to embryo and cancer cells the host immune system MDSC are also AFPR-positive. As the top cells in immune hierarchy MDSC are able to suppress both innate and adaptive immunity. Local accumulation of MDSC and AFP provides indulgence to cancer cells. MDSC depletion can awake innate immunity NK and adaptive immunity T-cells to destroy cancer cells. One of the ways to deplete MDSC is AFP-toxin drug. Combined action of innate and adaptive immunity plus targeted chemotherapy all provided by AFP-toxin drug is beneficial for cancer patients.

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“…This enables the innate and adaptive immunity to destroy cancer cells and metastases [7]. This ‘Achilles-heel’ of cancer [8] was discovered and used by Govallo who achieved a 77.1% 5-year survival rate, and a 65.4% 10-year, or more, survival rate in 35 terminal patients after vaccination with the placental proteins [9], the majority of which comprised oncofetal AFP and AFPR.…”

mentioning

confidence: 99%

Achilles Heel of Cancer

Cited by 3 publications

References 12 publications

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

Cancer Is the Innate Immunity Fault

Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Through AFP-Binding Receptors

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