Magic Bullet and Immunotherapy against Metastasis

Pak, Vladimir

doi:10.15406/jcpcr.2016.06.00206

Cited by 5 publications

(5 citation statements)

References 24 publications

(25 reference statements)

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“…It also retrospectively explains our previous results in metastases treatments with AFP-toxin drugs [34,35]. These good results assumed to be due to a summary action of the targeted chemotherapy and MDSCimmunotherapy [36].…”

Section: Introductionmentioning

confidence: 65%

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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Section: Introductionmentioning

confidence: 65%

Cancer Is the Innate Immunity Fault

Pak¹

2017

CTOIJ

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“…On the opposite, depleting MDSC by AFP-toxin drug can reverse immune suppression. MDSC-targeted immunotherapy is a new type of immunotherapy [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…with chemotherapy. AFPR was detected on majority of cancer cells that is why AFP-toxin drug already works as combination of the targeted chemotherapy [13] and MDSC-targeted immunotherapy [10]. Nevertheless, the immunotherapy impact is much more powerful because one magic bullet (targeted chemotherapy) can hit only one MDSC or cancer cell while MDSC depletion has greater consequences.…”

Section: Introductionmentioning

confidence: 99%

Achilles Heel of Cancer

Pak¹

2017

CTOIJ

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Immunotherapy is the most promising trend in cancer treatments. Checkpoint inhibitors block the blocking molecules, enabling T-cells to target the cancer. MDSC-targeted immunotherapy is a new type of immunotherapy that depletes the blocking cells, enabling NK and T-cells to target the cancer. MDSC accumulates in tumor places and suppresses both adaptive and innate immunity. An oncofetal protein -AFPR -was found on host MDSC as well as on majority of cancer cells. This receptor can internalize its ligand: another oncofetal protein -AFPloaded with nutrients. AFP can be cancer, host or artificial origin; it accumulates in tumor places where it works in a shuttle manner feeding both cancer cells and MDSC. On the opposite, toxin being delivered by AFP instead of nutrient through AFPR depletes MDSC that in its turn unleashes subordinate executive cells both of innate and adaptive immunity to destroy cancer cells. Unlike adaptive immunity T cells innate immunity NK are capable to destroy cancer stem cells that prevent metastases. AFP-toxin drugs can be used to treat metastases, early stage cancers and cancer prophylactics. The use of oncofetal proteins is Achilles hill of cancer and should be reversed against it.

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“…Vaccination of cancer patients with AFP, AFPR and AFP–AFPR complexes can raise an immune response that depletes AFPR-positive MDSCs (as well as cancer cells). 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%

“…AFP-toxin complexes that selectively target MDSCs through AFP-binding receptors could become a necessary tool for cancer/metastases treatments and could be used as monotherapy or combined with other immunotherapies and chemotherapies. As a matter of fact, the AFP–toxin complex itself works as the combination of MDSC-targeted immunotherapy and cancer cells-targeted chemotherapy [7] and is remarkably promising. Unlike T-cell immunotherapies, MDSC-targeted immunotherapy is not personalized and consequently could be more affordable for cancer patients.…”

mentioning

confidence: 99%

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

Pak¹

2018

Future Sci. OA

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Magic Bullet and Immunotherapy against Metastasis

Cited by 5 publications

References 24 publications

Cancer Is the Innate Immunity Fault

Cancer Is the Innate Immunity Fault

Achilles Heel of Cancer

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

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