Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

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TimGDixon
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Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by TimGDixon »

Even though its contained in PR here is a direct link to submitted prepublication https://therapeuticsolutionsint.com/CV/ ... -01274.pdf
rrao11
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by rrao11 »

Tim,

This is awesome! This has soooooo much potential, I am hopeful that the market and the shareholders realize the magnitude and value of this.

I shared it with entire family/community of physicians. I know they’ll love it.

Go $tsoi!
curncman
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by curncman »

Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication
Company Advances its Clinical Stage Cancer Immunotherapy Candidate into Battle with Coronavirus

Jul 07, 2020, 09:00 ET

OCEANSIDE, Calif., July 7, 2020 /PRNewswire/ — Therapeutic Solutions International, Inc., (OTC Markets: TSOI), announced submission of a publication providing preclinical data which supports repositioning of its Cancer Immunotherapy StemVacs™ as a candidate for treatment of COVID-19. StemVacs™ is based on activating universal donor immune system cells called dendritic cells in a manner so that upon injection they reprogram the body’s “Natural Killer” cells.

Natural killer cells are the most potent cell type in the body in terms of killing viruses. Unfortunately, natural killer cells also produce chemicals called cytokines which at high concentrations can be lethal. The current data suggests that StemVacs™ can activate natural killer cells while at the same time suppressing lung inflammation. This dual mechanism of action makes StemVacs™ a promising candidate for treatment of coronavirus.

“The activation of natural killer cells caused by StemVacs™ was so significant that we were able to obverse inhibition of tumor growth. The data submitted today strongly suggest the possibility of using our immunotherapy in COVID-19, but also supports the original disease indication of StemVacs™ which is oncology” said Dr. James Veltmeyer, first author on the publication and Chief Medical Officer of the Company. “Many immunotherapies possess the potential side effect of what is called cytokine storm. Interestingly, our immunotherapy actually seems to suppress pathological inflammation.”

The authors of the paper discussed the concept of a potential “tolerogenic loop” in which the dendritic cells are activating natural killer cells but also stimulating generation of T regulatory cells which act to protect the lung from excess inflammation.

“Given that StemVacs™ already has an IND number with the FDA, the studies that we need to undertake to initiate our COVID-19 repositioning need only to support potential efficacy. We believe that the data we are submitting for publication strongly supports efficacy” said Timothy Dixon, President and CEO of the Company. “We are in the process of collecting data from patients treated with StemVacs for cancer and once these data are properly presented, we hope to file an IND amendment to request the FDA to allow us to initiate clinical trials in coronavirus.”
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TimGDixon
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

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Below is our closing discussion of StemVacs2 paper with a few highlights. Of the two authors mentioned below, one is none other than our own Dr. Ichim. I have provided the abstract to the referenced paper at the bottom and a link to the full paper. I forgot to ask, have the "flinstones" come up with anything yet?

Discussion https://therapeuticsolutionsint.com/CV/ ... -01274.pdf
We have demonstrated that transfer factor activated DC are capable of inducing potent immunity by stimulating both T and NK cells. The current data support the translational use of StemVacs™ in treatment of COVID-19 due to its unique ability to activate NK cells but also suppress inflammation in the lungs.

Pulmonary inflammation such as in ARDS is associated with augmentation of interleukin-17 [29, 30]. It is known that the cells which produce IL-17, called Th17 cells, have a reciprocal relationship with T regulatory cells. Indeed it may be possible that our dendritic cell therapy was stimulating NK cells which account for its anticancer properties, while stimulating T regulatory cells, which may have been responsible for reduction of inflammation.

In many situations it is established that mature DC activate T cells while immature ones generate T regulatory cells. Two of the authors (WPM and TEI) more than ten years ago described the Tolerogenic Feedback Loop in which permanent allograft tolerance is maintained through a self-amplifying loop between regulatory T cells and tolerogenic dendritic cells [31]. We believe that further experiments are needed to determine whether the suppression of pulmonary inflammation is occurring as a result of T regulatory cells being elicited.

While utilization of autologous dendritic cells is well-known in the area of oncology, allogeneic dendritic cells present the tantalizing option of an “off the shelf” therapy. Initial clinical reactions using this approach have demonstrated safety (manuscript in preparation) and signals of efficacy. It may be that allogeneic dendritic cells work by activating NK cells as compared to T cells. Further studies are needed to elucidate whether it is the allogeneic nature of the stimulating cells, or whether it is the potency of the TF in activating DC.

One unexplained observation was the finding that while TF stimulated expression of costimulatory molecules in a manner superior to LPS and TNF-alpha, it did not stimulate IL-12 production. IL-12 is needed for NK activation, however NK activation was higher with TF as compared to traditional means of activating dendritic cells. We postulate that other cytokines may be involves such as IL-18, which we are in the process of assessing.

In conclusion, StemVacs™ appears to be a novel means of stimulating innate immunity while concurrently suppressing cytokine storm and pathology associated with adaptive immunity. These current data will serve to provide preclinical support for the planned StemVacs™ IND application.

29. Hagau N, Slavcovici A, Gonganau DN, Oltean S, Dirzu DS, Brezoszki ES, Maxim M, Ciuce C, Mlesnite M, Gavrus RL et al: Clinical aspects and cytokine response in severe H1N1 influenza A virus infection. Crit Care 2010, 14(6):R203.
30. Holloway TL, Schwacha MG: The Th-17 response and its potential role in post-injury pulmonary complications. Int J Burns Trauma 2012, 2(1):11-17.

31. Min WP, Zhou D, Ichim TE, Strejan GH, Xia X, Yang J, Huang X, Garcia B, White D, Dutartre P et al: Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. J Immunol 2003, 170(3):1304-1312.

https://www.jimmunol.org/content/170/3/1304.full

Abstract
An active role of T regulatory cells (Treg) and tolerogenic dendritic cells (Tol-DC) is believed important for the induction and maintenance of transplantation tolerance. However, interactions between these cells remain unclear. We induced donor-specific tolerance in a fully MHC-mismatched murine model of cardiac transplantation by simultaneously targeting T cell and DC function using anti-CD45RB mAb and LF 15-0195, a novel analog of the antirejection drug 15-deoxyspergualin, respectively. Increases in splenic Treg and Tol-DC were observed in tolerant recipients as assessed by an increase in CD4+CD25+ T cells and DC with immature phenotype. Both these cell types exerted suppressive effects in MLR. Tol-DC purified from tolerant recipients incubated with naive T cells induced the generation/expansion of CD4+CD25+ Treg. Furthermore, incubation of Treg isolated from tolerant recipients with DC progenitors resulted in the generation of DC with Tol-DC phenotype. Treg and Tol-DC generated in vitro were functional based on their suppressive activity in vitro. These results are consistent with the notion that tolerance induction is associated with a self-maintaining regulatory loop in which Tol-DC induce the generation of Treg from naive T cells and Treg programs the generation of Tol-DC from DC progenitors.
Howzitgoing
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by Howzitgoing »

Potentially huge.

To add, edit slightly, StemVacs™ appears to be a novel means of stimulating innate immunity via both T and NK cells while concurrently suppressing cytokine storm ...

To help those of us who aren't virologists, interesting article, which explains the significance of T cells:

NYTimes
https://tinyurl.com/y24c5ps4
The Coronavirus Is New, but Your Immune System Might Still Recognize It
> Some people carry immune cells called T cells that can capitalize on the virus’s resemblance to other members of its family tree.

,,, to some of our immune cells, the virus was already something of a familiar foe.

A flurry of recent studies has revealed that a large proportion of the population — 20 to 50 percent of people in some places — might harbor immunity assassins called T cells that recognize the new coronavirus despite having never encountered it before.

These T cells, which lurked in the bloodstreams of people long before the pandemic began, are most likely stragglers from past scuffles with other, related coronaviruses, including four that frequently cause common colds. It’s a case of family resemblance: In the eyes of the immune system, germs with common roots can look alike, such that when a cousin comes to call, the body may already have an inkling of its intentions.

[More]
curncman
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by curncman »

Howitzgoing, Nice correlation to the conclusion of Stemvacs2 as potent vaccine to COVID-19, SARS and ARDS....Vallah there you have it folks TSOI is coming with their COVID-19 vaccine ready far superior than any Pharoah's vaccine in trials...GO TSOI! GO STEMVACS!
curncman
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Stemvacs2 activates NK and T cells ?

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Tim, can you please clarify for us if stemvacs2 activates NK cells (reduces inflammation in lungs) and also Tcells (reduces cancer) ?
It may be that allogeneic dendritic cells work by activating NK cells as compared to T cells.
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TimGDixon
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by TimGDixon »

Transfer Factor (TF) was generated according to previously published protocols and added to dendritic cell progenitors. As seen in Figure 1, dendritic cells activated with TF possessed higher expression of CD80 (Fig 1a), higher expression of CD86 (Fig 1b), lower expression of IL-12 (Fig 1c) and possessed enhanced ability to stimulate NK cytotoxicity (Fig 1d).
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One therapeutic possibility for cell therapies which activate NK cells could be in the treatment of COVID19. One of the potential drawbacks of utilizing immunotherapies in this condition is the possibility of cytokine storm and exaggeration of pulmonary failure.

Accordingly, we sought to assess whether administration of StemVacs™ would exacerbate inflammatory reactions subsequent to endotoxin challenge. To our surprise StemVacs™ administration was associated with enhanced protection from lung inflammation as compared to conventionally activated DC which actually enhanced inflammation (Figure 3).
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curncman
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Re: Therapeutic Solutions International Submits Publication on StemVacs™ Preclinical Data Supporting COVID-19 Indication

Post by curncman »

Tim, thanks for the confirmation. Stemvacs2 clearly supports NK and T1 cells activation while suppressing the inflammation also increases immunity. its HUGE NEWS for the COVID-19 CDC staff to take closer look at STEMVACS now.
curncman
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The Treatment That Could Crush Covid Early trials show signaling cells eliminate the virus, calm the immune response and

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https://www.wsj.com/articles/the-treatm ... 1597360709

The Treatment That Could Crush Covid
Early trials show signaling cells eliminate the virus, calm the immune response and repair tissue damage.

More than 500 clinical trials are under way world-wide in the race to find an effective treatment for Covid-19. Everybody wants it; nobody has it—yet. But one of the most promising therapies for Covid-19 patients uses “medicinal signaling cells,” or MSCs, which are found on blood vessels throughout the body.
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