05-24-2021 Immunotherapies for Targeting of Tumor Vasculature

https://therapeuticsolutionsint.com/the ... cs-v-ipsc/

Disclosed are novel means, protocols, and compositions of matter for creating targeted immune responses and/or induction of immunological memory towards the tumor vasculature. In one embodiment pluripotent stem cells are transfected with one or more genes capable of eliciting immunity, induced to differentiate into endothelial-like cells which resemble the tumor endothelial cells, and utilized as a vaccine. In some embodiment’s genes are engineered under control of specific promoters to allow for various specificities of activity. In one specific embodiment pluripotent stem cells engineered to endow properties capable of inducing expression of the α-Gal epitope (Galα1,3Galα1,4GlcNAc-R). Addition of adjuvants to enhance antigen presentation of the vaccine composition, as well as means of stimulating systemic enhancement of circulating endothelial specific T cells are also disclosed.

03-29-2021 Compositions Capable of Stimulating Immunity Towards Tumor Blood Vessels

https://therapeuticsolutionsint.com/the ... ntibodies/

Disclosed are novel means, protocols, and compositions of matter for eliciting an immune response against blood vessels supplying neoplastic tissue. In one embodiment pluripotent stem cells are transfected with one or more genes capable of eliciting immunity. In some embodiments such genes are engineered under control of specific promoters to allow for various specificities of activity. In one specific embodiment pluripotent stem cells engineered to endow properties capable of inducing expression of the α-Gal epitope (Galα1,3Galα1,4GlcNAc-R).

03-23-2021 Chimeric Cells Comprising Dendritic Cells and Endothelial Cells Resembling Tumor Endothelium

https://therapeuticsolutionsint.com/the ... d-vessels/

Disclosed are means, methods and compositions of matter useful for induction of immunological responses towards tumor endothelial cells. In one embodiment the invention teaches fusion of dendritic cells and cells resembling tumor endothelial cells and administration of such chimeric cells as an immunotherapy for stimulation of tumor endothelial cell destruction. In other embodiments pluripotent stem cells are utilized to generate dendritic cells, wherein said dendritic cells are fused with pluripotent stem cell derived endothelial cells created in a manner to resemble tumor endothelial cells.


03-16-2021 Pluripotent Stem Cell Derived Dendritic Cells and Engineered Dendritic Cells for Cancer Immunotherapy

https://therapeuticsolutionsint.com/the ... temvacs-v/

Disclosed are populations of dendritic cells generated from stem cells capable of inducing immunity towards cancer. In one embodiment said dendritic cells are generated from allogeneic inducible pluripotent stem cells, for some uses, said pluripotent stem cells are genetically engineered/edited to induce cancer specific immunity and/or resist immunosuppressive effect of tumor derived microenvironment. In one embodiment pluripotent stem cells are transfected with cancer stem cell antigens such as BORIS and/or NR2F6.

02-22-2021 Ex Vivo Generation of Immunocytes Recognizing Brother of the Regulator of Imprinted Sites (BORIS) Expressing Cancer Stem Cells

https://therapeuticsolutionsint.com/the ... tem-cells/

Disclosed are means, methods and compositions of matter useful for induction of immunity towards cancer stem cells by providing a dendritic cell, wherein said dendritic cells express BORIS and/or peptides derived from BORIS, wherein said dendritic cell is cultured in the presence of one or more immunocytes. In one embodiment said dendritic cells are derived from umbilical cord blood sources and allogeneic to T cells, which are expanded ex vivo and used for the purposes of immunotherapy.

02-08-2021 Stimulation of Natural Kill Cell Memory by Administration of Dendritic Cells

https://therapeuticsolutionsint.com/the ... to-cancer/

Disclosed are means, methods and compositions of matter useful for induction of natural killer cell memory by administration of dendritic cells and/or exosomes thereof. In one embodiment a mammal suffering from cancer is administered allogeneic cord blood derived dendritic cells that are not pulsed exogenously. In one embodiment the dendritic cells are stimulated to possess chemotactic activity towards the tumor by culture of dendritic cell progenitors in hypoxia. Natural killer cell memory is induced, in part, by triggering of upregulation of cytokines associated with homeostatic expansion such as interleukin 7 and interleukin 15.

01-26-2021 Stimulation of Dendritic Cell Activity by Homotaurine and Analogues Thereof

https://therapeuticsolutionsint.com/the ... motaurine/

Disclosed are means, methods, and compositions of matter useful for enhancement of dendritic cell activity. In one embodiment the invention provides the use of GABA agonists such as homotaurine for stimulation of dendritic cell activity. In one embodiment said dendritic cell activity is enhancement of natural killer cell activity and/or of T cell activity. In one embodiment NK cell activity is ability to induce cytotoxicity in neoplastically transformed cells, whereas T cell activity is either cytokine production for CD4 cells or cytotoxicity for CD8 cells.


06-30-2020 Augmentation of Natural Killer Cell Activity and Induction of Cytotoxic Immunity Using Leukocyte Lysate Activated Allogeneic Dendritic Cells: StemVacs™

https://therapeuticsolutionsint.com/the ... ine-storm/

Stimulation of immunity would be beneficial in various chronic conditions such as viral infections and neoplasia. Autologous dendritic cell therapy has been widely described in the immunotherapy literature and has been approved by the FDA for treatment of prostate cancer. Unfortunately, the need to generate individual doses is costly and limited by ability of the patients to have sufficient starting cell numbers available to generate sufficient dendritic cells. Here we describe the process of preparing allogeneic dendritic cells utilizing a leukocyte lysate based approach. These data support development of StemVacs for conditions that would benefit from NK activation such as cancer and COVID-19.

An Open-Label Single-Arm, Monocentric Study Assessing the Efficacy and Safety of Natural Pterostilbene (Pterocarpus marsupium) for Skin Brightening and Antiaging Effects

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999773/

Abstract
Background
Both intrinsic and environmental factors play a role in premature ageing of the skin. Natural extracts have been extensively used to reduce the signs of ageing in recent years. Pterostilbene is a natural analog of resveratrol with therapeutic properties against numerous diseases mainly due to its ability to reduce reactive oxygen species.

Methods
We studied the anti-aging and skin brightening effect of a 0.4% formulation of natural pterostilbene in healthy volunteers (N=38) in an open-label, single-arm, monocentric study for 8 weeks. The melanogenesis inhibitory, anti-tyrosinase and anti-collagenase and anti-elastase properties of pterostilbene were evaluated in vitro.

Results
Natural pterostilbene showed significant inhibition of melanogenesis in vitro. Pterostilbene cream (0.4%) was highly effective in reducing markers of aging and induces even skin tone. The product was effective in reducing wrinkles and fine lines, improved skin hydration elasticity and showed no adverse effects.

Conclusion
Our results suggest that natural pterostilbene is a safe and effective ingredient for use in cosmetic preparation to reduce the markers of skin ageing and brighten the skin tone.

Trial Registration
Clinical Trial Registration India Identifier CTRI/2019/01/017160 [Registered on 18/01/2019].

NanoStilbene Cream

This unscented body cream offers carefully selected plant-based ingredients. It spreads easily and absorbs fast, providing nourishment in abundance. It soothes dry skin, sensitive skin, and adds plenty of moisture to keep the skin supple, healthy, and youthful. A unique formulation of Soy, Jojoba, Coconut and Palm extracts that restores skin's natural balance for radiant health. In addition, this cream contains Patented NanoStilbene, a potent antioxidant and anti-inflammatory made with Nanoparticle Pterostilbene.

Pterostilbene (PTER) is a natural compound predominantly found in blueberries. Studies show that PTER is an effective anti-oxidative and anti-inflammatory agent.

Allergic contact dermatitis (ACD) is an important occupational disease caused mainly by topical exposure to hexavalent chromium (Cr(VI)), an impurity of cement manufacture. In Europe, the prevalence of ACD is approximately 4–5% in cement workers [1]. In some Asian countries the prevalence is even higher, such as 40% in Singapore and 13% in Taiwan [2,3]. Due to its high prevalence, ACD exerts an important occupational health impact on those workers. The pathologic process of ACD has been well defined as a cell-mediated type IV hypersensitivity reaction in which many cell types are involved, including keratinocytes, dendritic cells, T-lymphocytes and leucocytes [4]. Reactive oxygen species (ROS) activation was proposed as the initial event, as it leads to the activation of transcriptional factors and signaling pathways, including NF-κB and p38 mitogen-activated protein kinase (MAPK) pathway, which leads to the release of pro-inflammatory cytokines such as TNF-α and IL-1β [5,6,7]. Interestingly, the p38-downstream kinase MAPK-activated protein kinase 2 (MK2) has recently been explored in inflammatory disorders of the skin, such as psoriasis and has become a therapeutic strategy for anti-inflammatory disease. Disruption of MK2 signaling leads to a significant reduction in the level of several pro-inflammatory cytokine production [8]. ROS are also involved in the activation of the NLRP3 inflammasome, which is required to direct the proteolytic maturation of inflammatory cytokines, such as IL-1β and IL-18. Recent studies have indicated that the NLRP3 inflammasome is often wrongly activated by environmental irritants, thus resulting in cutaneous inflammatory diseases [9]. Moreover, ROS can facilitate the process of ACD by changing the extracellular microenvironment [10]. When skin is exposed to Cr(VI), it can penetrate and bind to keratinocytes and immune cells. The intracellular reduction of Cr(VI) is associated with the production of ROS, leading to dermal toxicity, cytokine excretion and skin hypersensitivity [1].

Contains: Water, Vegetable Glycerin, Stearic Acid, Myristyl Myristate, Cetearyl Alcohol, Ceteareth-20, Glycerol Stearate, Simmondsia Chinensis, (Jojoba) Seed Oil, Glycerin Soja (Soybean) Oil, Cetyl Alcohol, Acrylates/C10-30 Alkyl Acrylate Crosspolymer, Butyrospermum Parkii (Shea) Butter, Calendula Officials Flower Oil, Passiflora Edulis (Passion Fruit) Seed Oil, Oryza Sativa (Rice) Bran Oil, Euterpe Oleracea (Acai Palm) Fruit Oil, Phenoxethanol, Ethylhexylglycerin, NanoStilbene.
References
1. Shelnutt, S.R.; Goad, P.; Belsito, D.V. Dermatological toxicity of hexavalent chromium. Crit. Rev. Toxicol. 2007, 37, 375–387.
2. Goh, C.L.; Gan, S.L.; Ngui, S.J. Occupational dermatitis in a prefabrication construction factory. Contact Dermat. 1986, 15, 235–240.
3. Guo, Y.L.; Wang, B.J.; Yeh, K.C.; Wang, J.C.; Kao, H.H.; Wang, M.T.; Shih, H.C.; Chen, C.J. Dermatoses in cement workers in southern Taiwan. Contact Dermat. 1999, 40, 1–7.
4. Toncic, R.J.; Lipozencic, J.; Martinac, I.; Greguric, S. Immunology of allergic contact dermatitis. Acta Dermatovenerol. Croat. 2011, 19, 51–68.
5. Fuchs, J.; Zollner, T.M.; Kaufmann, R.; Podda, M. Redox-modulated pathways in inflammatory skin diseases. Free Radic. Biol. Med. 2001, 30, 337–353.
6. Matos, T.J.; Duarte, C.B.; Goncalo,M.; Lopes,M.C. Role of oxidative stress in ERK and p38MAPK activation induced by the chemical sensitizer DNFB in a fetal skin dendritic cell line. Immunol. Cell Biol. 2005, 83, 607–614.
7. Chao, W.; Deng, J.-S.; Huang, S.-S.; Li, P.-Y.; Liang, Y.-C.; Huang, G.-J. 3,4-dihydroxybenzalacetone attenuates lipopolysaccharide-induced inflammation in acute lung injury via down-regulation of MMP-2 and MMP-9 activities through suppressing ROS-mediated MAPK and PI3K/AKT signaling pathways. Int. Immunopharmacol. 2017, 50, 77–86.
8. Singh, R.K.; Najmi, A.K.; Dastidar, S.G. Biological functions and role of mitogen-activated protein kinase activated protein kinase 2 (MK2) in inflammatory diseases. Pharmacol. Rep. 2017, 69, 746–756.
9. Chen, R.J.; Lee, Y.H.; Yeh, Y.L.; Wang, Y.J.; Wang, B.J. The Roles of Autophagy and the Inflammasome during Environmental Stress-Triggered Skin Inflammation. Int. J. Mol. Sci. 2016.
10. Corsini, E.; Galbiati, V.; Nikitovic, D.; Tsatsakis, A.M. Role of oxidative stress in chemical allergens induced skin cells activation. Food Chem. Toxicol. 2013, 61, 74–81.

Immunotherapies. More proof that TSI is in the right scientific-miracles field.

A recent drug trial administered to a handful of cancer patients had the surprising result of eliminating the disease in every participant involved.

Huh? ELIMINATED the disease?

The study was conducted on 18 rectal cancer patients at Memorial Sloan Kettering Cancer Center in Manhattan and had a 100 percent success rate, according to a paper published Sunday in the New England Journal of Medicine.

Whaaaat? 100 percent success rate?

“I believe this is the first time this has happened in the history of cancer,” Dr. Luis A. Diaz Jr, the author of the paper, told the New York Times.

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The study was conducted on 18 rectal cancer patients at Memorial Sloan Kettering Cancer Center in Manhattan and had a 100 percent success rate, according to a paper published Sunday in the New England Journal of Medicine.

Immunotherapy with monoclonal antibodies, such as dostarlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and dostarlimab may help to control the diseases.

Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as a medication for the treatment of endometrial cancer. Dostarlimab is a programmed death receptor-1 –blocking monoclonal antibody. Dostarlimab was approved for medical use in the United States and the European Union in April 2021.