StemVacs + BORIS

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TimGDixon
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StemVacs + BORIS

Post by TimGDixon »

I thought i would just give everyone a little backdrop on BORIS - there may still be a few people around that remember hearing about BORIS from us so who or what is BORIS?

The cancer–testis antigen BORIS (and the paralogue CTCFL) was discovered about 19 years ago. Normally in men BORIS is found in the testis and in no other tissues. However in the abnormal of cancer BORIS is present across most cancers. Dr. Ichim famously said that "a tumor that stops expressing boris is no longer a tumor" nails it. If its found in tissues outside the testis then it could be a early indicator of cancer or reveal actual cancer. Tumors express BORIS as long as they have a living cancer stem cell. We've developed a way of taking our allogeneic dendritic cell (StemVacs) approach to ex vivo (outside the body) and generate boris killing T cells.

Now in full disclosure this is not our first patent on BORIS but this is version 2.0 and begins as an allogeneic product (universal) rather than our autologous version (patient donated/self) thereby making this off the shelf universal product. The biggest difference though is the T effector cells we generated that are BORIS killers. This is really cool stiuff you giys - we've been working on boris for years and years and Dr. Ichim goes back to the very beginning publishing with the guy who discovered it and I have provided those 3 papers below for you to read. Im going to tell you more but in a second post.


Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant.
Loukinov D, Ghochikyan A, Mkrtichyan M, Ichim TE, Lobanenkov VV, Cribbs DH, Agadjanyan MG.
J Cell Biochem. 2006 Aug 1;98(5):1037-43. doi: 10.1002/jcb.20953.
PMID: 16741971 https://pubmed.ncbi.nlm.nih.gov/16741971/

Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer-testis antigen, brother of the regulator of imprinted sites.
Ghochikyan A, Mkrtichyan M, Loukinov D, Mamikonyan G, Pack SD, Movsesyan N, Ichim TE, Cribbs DH, Lobanenkov VV, Agadjanyan MG.
J Immunol. 2007 Jan 1;178(1):566-73. doi: 10.4049/jimmunol.178.1.566.
PMID: 17182597 Free PMC article. https://pubmed.ncbi.nlm.nih.gov/17182597/

DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice.
Mkrtichyan M, Ghochikyan A, Loukinov D, Davtyan H, Ichim TE, Cribbs DH, Lobanenkov VV, Agadjanyan MG.
Gene Ther. 2008 Jan;15(1):61-4. doi: 10.1038/sj.gt.3303044. Epub 2007 Nov 1.
PMID: 17972923 Free PMC article. https://pubmed.ncbi.nlm.nih.gov/17972923/
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TimGDixon
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Re: StemVacs + BORIS

Post by TimGDixon »

Dr. Loukinov published this paper in 2018 Targeting CTCFL/BORIS for the immunotherapy of cancer https://pubmed.ncbi.nlm.nih.gov/30390146/
and had this to say:

"Recently CTCFL/BORIS has received additional attention as a target expressed in cancer stem cells (CSC). These cells drive tumor growth recurrence, metastasis, and treatment resistance. CTCFL/BORIS silencing leads to senescence and death of CSC. Therefore, an immunotherapeutic strategy that targets CTCFL/BORIS may lead to the selective destruction of CSC and potential eradication of metastatic disease."

We have thought a lot about this since 2018 when that paper was published and today we told all of you we figured out how to do it and it is novel enough to file patent app. Admittedly i was disappointed at how the market responded but tomorrow is a new day.

Let me show you a few examples.

Stimulation of Immunity to CD133 Positive PC-3 Cancer Stem Cells

Cord blood generated allogeneic dendritic cells were obtained by culture of adherent monocytes with GM-CSF (100 IU/ml) and IL-4 (100 IU/ml) for 7 days. Cells expressed CD11c and possessed typical dendritic morphology. Cells were incubated with full length BORIS protein and treated with 30 ng/ml Poly (IC) for 24 hours to induce dendritic cell maturation. Dendritic cells were cultured with allogeneic peripheral blood mononuclear cells for 7 days in the presence of IL-2 (10 IU/ml) and anti-CD3 and anti-CD28 beads (10(5) beads per ml. T cells where purified by Magnetic Activated Cell Sorting for CD3 (containing both CD8 and CD4 cells). PC-3 prostate cancer cells where cultured and separated into either control (no T cells added), unfractionated, CD133 negative and CD133 positive. Cells where co-cultured at a 1:1 ratio and cytotoxicity was determined by MTT assay.
As observed, T cells possessed a preferential ability to kill CD133 cells, which corresponds to cancer stem cell phenotype.

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Stimulation of Immunity to flk Positive PC-3 Cancer Stem Cells

Cord blood generated allogeneic dendritic cells were obtained by culture of adherent monocytes with GM-CSF (100 IU/ml) and IL-4 (100 IU/ml) for 7 days. Cells expressed CD11c and possessed typical dendritic morphology. Cells were incubated with full length BORIS protein and treated with 30 ng/ml Poly (IC) for 24 hours to induce dendritic cell maturation. Dendritic cells were cultured with allogeneic peripheral blood mononuclear cells for 7 days in the presence of IL-2 (10 IU/ml) and anti-CD3 and anti-CD28 beads (10(5) beads per ml. T cells were purified by Magnetic Activated Cell Sorting for CD3 (containing both CD8 and CD4 cells). PC-3 prostate cancer cells were cultured and separated into either control (no T cells added), unfractionated, flk negative and flk positive. Cells where co-cultured at a 1:1 ratio and cytotoxicity was determined by MTT assay.
As observed, T cells possessed a preferential ability to kill CD133 cells, which corresponds to cancer stem cell phenotype.

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Stimulation of Immunity to Rhodamine Positive PC-3 Cancer Stem Cells

Cord blood generated allogeneic dendritic cells were obtained by culture of adherent monocytes with GM-CSF (100 IU/ml) and IL-4 (100 IU/ml) for 7 days. Cells expressed CD11c and possessed typical dendritic morphology. Cells were incubated with full length BORIS protein and treated with 30 ng/ml Poly (IC) for 24 hours to induce dendritic cell maturation. Dendritic cells were cultured with allogeneic peripheral blood mononuclear cells for 7 days in the presence of IL-2 (10 IU/ml) and anti-CD3 and anti-CD28 beads (10(5) beads per ml. T cells were purified by Magnetic Activated Cell Sorting for CD3 (containing both CD8 and CD4 cells). PC-3 prostate cancer cells where cultured and separated into either control (no T cells added), unfractionated, Rhodamin negative and Rhodamin positive. Cells where co-cultured at a 1:1 ratio and cytotoxicity was determined by MTT assay.
As observed, T cells possessed a preferential ability to kill CD133 cells, which corresponds to cancer stem cell phenotype.
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TimGDixon
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Re: StemVacs + BORIS

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So in those three examples we said T cells possessed a preferential ability to kill CD133 cells, which corresponds to cancer stem cell phenotype. So what is CD133? It's a glycoprotein found in humans that gets encoded by a gene called PROM1. CD133 has been found in 82% of the cancer genome. In this paper CD133: beyond a cancer stem cell biomarker https://pubmed.ncbi.nlm.nih.gov/29911902/ the authors says:

"CD133 (prominin-1), a pentaspan membrane glycoprotein, is one of the most well-characterized biomarkers used for the isolation of cancer stem cells (CSCs). The presence of CSCs is one of the main causes of tumour reversal and resilience...Therefore, CD133 could be considered to be an 'Achilles' heel' for CSCs, because by inhibiting this protein, the signalling pathways that are involved in cell proliferation will also be inhibited. By understanding the molecular biology of CD133, we can not only isolate stem cells but can also utilise it as a therapeutic strategy."

So the fact that we effectively killed CD133 this has broad application to a variety of cancers across the genome where CD133 is found. So the markets may not have recognized the significance of this i hope you do now.
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TimGDixon
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Re: StemVacs + BORIS

Post by TimGDixon »

There is just too much literature to share it here but heres a couple of links

CD133 has over 6,000 papers published
https://pubmed.ncbi.nlm.nih.gov/?term=cd133

and for BORIS about 2800 papers
https://pubmed.ncbi.nlm.nih.gov/?term=boris
TaylorBurton24
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Re: StemVacs + BORIS

Post by TaylorBurton24 »

Tim, this is excellent due diligence on behalf of the company and the investors appreciate it I’m sure. Very very interesting and I am sure hoping that therapeutic solutions will be an impact player globally in the fight against cancer.

Tim I would like to make a few points here. See if you could address these if you don’t mind.

1) The PR that went out this a.m was powerful; StemVacs might be the cure for cancer! :) However, the share price fell and I am wondering yet again, if being on the pink sheets is actually hurting TSOI indirectly! I do think todays new was a litmus test and the news just might have been not taken seriously and the share price retracted down. Perhaps IMHO if TSOI traded on a more respectable exchange such as the OTCQB or OTCQX, this might have had a different impact.

2) If we have a hunch that the investment community is yawning at some of these news releases, would it be an idea to include potential revenues for the company if a StemVacs is adopted after positive outcomes from its ph 3 trial? And what type of appetite the world might have for your technologies and perhaps state what this type of research could be worth ... in the millions/billions? Investors might want to see a valuation on the potential of.... for example... a StemVacs. Perhaps in future PR’s You could allude to the size of the cancer market and potential revenues.

Here is an example if you don’t mind me suggesting this...

“The Global Metastatic Cancer Treatment Market is projected to be worth USD 111.16 Billion by 2027, according to the current analysis by Emergen Research. The market is anticipated to witness growth owing to the increase in the medical needs of the patient affected by the disease. The market is driven by the growing incidences of breast cancer and its consistent recurrence. Advancement in technology has also impacted the demand for the market. The advent of innovative technologies and growing awareness among the population has boosted the demand for the treatment. However, the lack of effective treatment for the metastatic disease and serious side effects have hindered the growth of the market.“

Thank you for taking the time to read this. I look forward to hearing from you. In a nutshell, I believe we need to get off the pinks and onto a more respectable exchange, and I think investors need to know The financial size of the market you are hoping to target.

keep up the great work!
AC330
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Re: StemVacs + BORIS

Post by AC330 »

Great questions. I think it is mostly that so many folks purchased at a prices less than a penny and it is it difficult not to take some profits. In my case, I sold half and kept half. I love everything this about this company including you Tim but I can’t find myself purchasing my other half back until We raise the $100mm needed. Once there is more clarity on this, I have a feeling invesors will flock back in. I almost rather rip off the band aid and have clarity. It is the uncertainty that is driving the price down. Hope this doesnt offend but my two cents. I am a huge believer in Tim and team but this uncertainty is alive and well and once we squash it, to the moon!!!
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TimGDixon
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Re: StemVacs + BORIS

Post by TimGDixon »

TaylorBurton24 wrote: Mon Feb 22, 2021 6:13 pm Tim, this is excellent due diligence on behalf of the company and the investors appreciate it I’m sure. Very very interesting and I am sure hoping that therapeutic solutions will be an impact player globally in the fight against cancer.

Tim I would like to make a few points here. See if you could address these if you don’t mind.
Thanks for the questions. Let me see if i can give a reasonable response.

1) I don't think pink sheets is hurting us at this point, in fact it helps us to be who we are. QB/QX has requirements we could comply with (independent board members/audit committee/compensation committee) but my honest opinion is it would stifle and retard our work and innovation. We just moved our corporate headquarters to Idaho because the state of california was trying to dictate who is on our board and they don't care if we are grey sheets, pink sheets, OTCBB, QB,QX, NasDaq, NYSE... On Jan 1, 2021, we were facing $400,000 in fines in CA if we didn't comply - i'm not complying and were out of here. I'm heading to the property as soon as the snow melts to start building my new nutraceutical lab and the next year we are going to attempt to build our cellular lab - having a bunch of stuffy old independent people without a lick of vision isn't what i need to pull off these moves.

2) If anyone yawned at that press release they are foolish and naive and should find another issue to invest in. I only put out material pressers and i am sorry but my lawyer isn't going to ever let me pump a PR - about a year ago i mentioned rev's that were specific to the financial statement and we got a call from FINRA and the SEC on the same day - i am very careful about making predictions - we are pretty sober around here.

Whatever happened yesterday and the previous couple of days is MM manipulation - plain and simple - they see all those programmed trades and they trigger them and that starts the cascade - if you sold (or got sold) because of that i'm sorry but you might want to buy back in. I can't tell you where we will be a week from now or a year.

I know everyone wants me to say we're going to the moooooooooooooon - do you realize that had you bought on June 1st of last year and held until Feb 11 this year you would be up 6,718%? 10k last june was 200k on Feb 11... thats a 20 bagger
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TimGDixon
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Re: StemVacs + BORIS

Post by TimGDixon »

AC330 wrote: Mon Feb 22, 2021 6:42 pm Great questions. I think it is mostly that so many folks purchased at a prices less than a penny and it is it difficult not to take some profits.
Without a doubt you are going to have profit takers - and thats pretty groovy if you bought subpenny and got a dime - are you kidding me... look i could have very easily cleared 22,000,000 shares for selling and sold into the run last week at 10 cents, 15 cents, whatever, and took out a big chunk of equity from the market but i didn't and that should tell you guys everything - if you think i haven't worked my ass off for no pay for years and eaten a lot of PB&J sandwiches and slept a few hours a night non stop that i am not entitled to take some profits? But i didn't even though like the rest of you i could use the money.

Look you guys since May of last year we have given the company on average, two new patents a month. I would like someone to show me another co you are invested in that has done similar for you and i'll put some money over there - 22 new patent applications in 10 months. Most of the bio's have a single IP that they licensed from someone else - we invent our own technologies and we license others. A very famous stem cell guy called Dr. Ichim the other day and said i don't get it - how did Tim get Amit's cells because i have been trying for years and he won't give me the time of day even though i have published with him.. Tom replied 13 words... "Long live the Republic of Texas, do we have a deal or not"

So listen you guys i can't tell you where this will be but if you can't see me painting my masterpiece you need to change the angle of your view. BTW, do any of your other CEO's get up at 2am and answer hard questions from their investors? Can you show me just one? No, you don't get squat from those other CEO's because they are scared to death of you - i'm not - dig this - 2024 i'll throw i giant BBQ on our river property and you are all invited - how about that for something to look forward to?

Tim
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Last edited by TimGDixon on Tue Feb 23, 2021 3:33 am, edited 1 time in total.
Codycrusher
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Re: StemVacs + BORIS

Post by Codycrusher »

Hey Tim, I have so much faith in this company and I completely understand you, but what the guys said is in part, true. There are a lot of investors on a daily basis, new and not alike, who are weary about this company, being on the QB/QX market would have a impact in the share price tremendously through shear faith of the investor community being renewed, this would effect the company long term. I watch and involve myself in the boards daily, many investor boards and I can say for certainty, it’s a big hurt and a big boulder this company being a pink sheet, that’s a fact.
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TimGDixon
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Re: StemVacs + BORIS

Post by TimGDixon »

I understand but show me some of those QB/QX companies where the officers and directors are directly inventing the technologies they are bringing to market. Having a bunch of independent people to run rough-shod over me and my crew isn't going to produce more intellectual properties - look you guys we do bold cutting edge risky stuff and we need freedom to achieve that - can you imagine someone who isn't the inventor making decisions about where that technology goes when it us who have the vision and knowledge and experience. How about when we decided to provide stem cells to a comatose patient? Do you think that a bunch of outsiders would have approved that? How about me wanting to go to mexico like right now (just need the $) and treat another 10 patients with StemVacs - how easy do you think that would be to get approved by people who don't even understand what we do. I'll tell you what; when we hit a 50 billion dollar market cap we'll go to the Naz...

So what is it exactly that isn't transparent here about our operations that would be more transparent up there? We are fully reporting and i have 11 years of PCAOB audits behind me and im about to file the 10K for 2020 - i have personally written every single word of every 10Q and 10K we have filed over the year and signed all those 302/906 certifications under the penalty of perjury. We didn't just come on the scene so as i said when i deliver a 50 billion dollar market cap on the pink sheets we'll go north.
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