Breast Cancer Treatment with STEMVACS-V-iPSC-TEC +Nanostilbene

Post Reply
curncman
Posts: 564
Joined: Sat Mar 19, 2022 10:10 am

Breast Cancer Treatment with STEMVACS-V-iPSC-TEC +Nanostilbene

Post by curncman »

As of January 2022, there are more than 3.8 million women with a history of breast cancer in the U.S. This includes women currently being treated and women who have finished treatment. Breast cancer is the most commonly diagnosed cancer among American women.How many people are diagnosed with breast cancer worldwide? In 2020, more than 2.3 million women were diagnosed with breast cancer worldwide and 685,000 died.

In 2020, there were 2.3 million women diagnosed with breast cancer and 685 000 deaths globally. As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past 5 years, making it the world’s most prevalent cancer. There are more lost disability-adjusted life years (DALYs) by women to breast cancer globally than any other type of cancer. Breast cancer occurs in every country of the world in women at any age after puberty but with increasing rates in later life.

Breast cancer mortality changed little from the 1930s through to the 1970s. Improvements in survival began in the 1980s in countries with early detection programmes combined with different modes of treatment to eradicate invasive disease.
It is estimated that 43,780 deaths (43,250 women and 530 men) from breast cancer will occur in the United States this year. Worldwide, female breast cancer is the fifth leading cause of death. In 2020, an estimated 684,996 women across the world died from breast cancer.



What is the latest chemotherapy treatment?
The FDA has approved a form of gene therapy called CAR T-cell therapy. It uses some of your own immune cells, called T cells, to treat your cancer. Doctors take the cells out of your blood and change them by adding new genes so they can better find and kill cancer cells.

How fast does chemo shrink breast tumors?
A pair of drugs can dramatically shrink and eliminate some breast cancers in just 11 days, UK doctors have shown. They said the "surprise" findings, reported at the European Breast Cancer Conference, could mean some women no longer need chemotherapy.


The drug, called abemaciclib – brand name Verzenio – is now approved for patients with the HR+, HER2-early breast cancer, which makes up 70% of all breast cancers. The drug was already approved for advanced, or metastatic, breast cancer.

Can you take chemo pills for breast cancer?
Image result
Capecitabine (Xeloda) and cyclophosphamide (Cytoxan) are chemotherapy drugs approved and available in pill form for the treatment of breast cancer. In addition, targeted therapies may also be an option. Talk with your healthcare professional to determine the best solution for you.

What is in Keytruda?
Keytruda contains the drug pembrolizumab. It belongs to a class of drugs called PD-1 inhibitors. Keytruda is an immunotherapy drug, which means it tells certain parts of your immune system to attack cancer cells. Keytruda is given as an intravenous (IV) infusion by healthcare providers.

Is Methotrexate a chemo drug?
Methotrexate is one of a group of chemotherapy drugs called anti metabolites. These stop cells making and repairing DNA. Cancer cells need to make and repair DNA so that they can grow and multiply. Methotrexate stops the cells working properly.


Results presented at the American College of Rheumatology/Association of Rheumatology Professionals 2012 annual meeting show that adalimumab and methotrexate are more effective than DMARDs and prednisone in achieving remission in patients with early rheumatoid arthritis or undifferentiated arthritis patients.

Tim, The above are sum of the basic current medications and treatment options for Breast Cancer Patients. We would like to know how STEMVACS-V-iPSC+TEC in combination with NanoStilbene can offer better treatment option for curing Breast Cancer ?
I am well wisher of everyone! GOD will pardon all your sins but not your Central Nervous System! Think Positive!
User avatar
TimGDixon
Posts: 3871
Joined: Fri Mar 18, 2022 12:00 pm

Re: Breast Cancer Treatment with STEMVACS-V-iPSC-TEC +Nanostilbene

Post by TimGDixon »

Tim, The above are sum of the basic current medications and treatment options for Breast Cancer Patients. We would like to know how STEMVACS-V-iPSC+TEC in combination with NanoStilbene can offer better treatment option for curing Breast Cancer ?
As I posted in another thread yesterday, StemVacs-V is an interferon gamma pretreated allogeneic iPSC derived endothelial cell.

StemVacs-V for Metastatic Breast Cancer

The proposed study will assess feasibility and safety of an allogeneic therapeutic vaccine, StemVacs-V comprising inducible pluripotent stem cell (iPSC) derived endothelial-like cells generated under conditions designed to replicate the tumor microenvironment. StemVacs-V is designed to replicate tumor endothelial cells and induce immunity

Numerous preclinical studies in animal models, as well as 2 clinical studies, have demonstrated the feasibility of breaking tolerance to tumor associated endothelium, while not inducing cross-immunity towards healthy endothelium. Previous clinical studies have utilized human umbilical vein derived endothelial cells as a polyvalent immunogen, the current approach is modified in that iPSC-derived endothelial cells are utilized. This modification is performed based on: a) need for consistency of manufacturing; b) significantly higher amount of endothelial cells can be derived from the iPSC source as compared to umbilical cord; and c) ability for future generations of the vaccine to utilize molecular adjuvants. Additionally, the iPSC based StemVacs-V product is different than classical endothelial cell vaccines due to the step of pre-treatment with interferon gamma, which is performed in order to augment immunogenicity of tumor endothelial-like cells.

In the current study we seek to evaluate safety and signals of efficacy of StemVacs-V. Treatment protocol will comprise of 4 administrations of StemVacs-V, once per month, with each administration consisting of 4 separate intradermal administrations of 2.5 million cells in a volume of 1 ml. Therefore total cell dose will be 40 million cells, with 10 million cells administered per month.

Blockade of tumor angiogenesis is a therapeutically attractive target, which has been the basis of several FDA approved drugs such as Avastin. Numerous studies, preclinical and clinical, have demonstrated endothelial derived cells are capable of stimulating immunity towards tumor endothelium. Such an active immunity against polyvalent antigens offers the possibility of superior therapeutic results, with a decreased possibility of acquired resistance. StemVacs-V is an iPSC derived endothelial-based tumor vaccine which has demonstrated efficacy in animal models of breast cancer.

Immunological targeting of tumor endothelium is appealing based on: a) For every tumor endothelial cell therapeutically neutralized approximately 200-300 tumor cells perish, thus reducing the ability of tumors to lose expression of antigens; b) The immune system is in direct contact with the tumor endothelium, while immune access inside tumors is difficult due to areas of necrosis and high interstitial pressure; and c) Demonstrated prior efficacy of other anti-angiogenesis inhibitory compounds such as bevacizumab [1, 2].

Another further potential benefit of targeting the tumor associated vasculature is the potential of sensitizing tumors to radiotherapy [3], in part due to the selective thrombotic and apoptotic effects irradiation has on the tumor vasculature [4-7].

Angiogenesis, the outgrowth of new blood vessels from pre-existing capillaries and post-capillary venules, occurs during embryonic development, in the uterus during the menstrual cycle, in the process of wound healing, and in pathological conditions [8]. In healthy adults, endothelial cells can maintain a quiescent state for years, whereas they proliferate and migrate to form new vessels in response to inflammatory conditions and during tumor growth. Several studies have estimated that tumor associated endothelial cells proliferate 30-40 times faster relative to endothelial cells found in healthy vasculature [9-11]. Based on estimates that tumors fail to grow beyond 1-2 mm in the absence of new capillary growth, Dr. Judah Folkman put forth the central hypothesis that tumors release diffusible factors that stimulate endothelial cell proliferation in host capillary blood vessels [12]. Indeed, it has been estimated that eradication of one endothelial cell is capable of neutralizing of up to 100-300 tumor cells [13]. Since the immune system is in direct contact with the tumor vasculature, vaccination against tumor endothelium is theoretically very promising for breaching the immunological barriers created by the tumor microenvironment.

The goal in vaccination strategies is to raise immunity against antigens present in tumor endothelium while avoiding antigens that cross-react with healthy vasculature, thereby preventing deleterious autoimmune reactions. Since the landmark publication by Dr. Folkman, a catalog of molecular players involved in the process of tumor angiogenesis have been identified and characterized. However, clinical outcomes of traditional anti-angiogenic therapies such as monoclonal antibodies have improved patient survival rates only modestly [14]. Vaccination against endothelial cells is poised to overcome the existing problems of drug resistance and adverse side effects associated with other approaches. This report reviews vaccination strategies against the tumor endothelium that have been tested to date, including DNA, protein and peptide vaccines using tumor-endothelium-associated antigens, as well as polyvalent vaccines comprised of whole endothelial cells. Very encouraging data point toward the efficacy of vaccination in raising humoral and cell-mediated immunity against angiogenesis-associated antigens in cancer. In this discussion, we also highlight our novel approach wherein placenta-derived endothelial cell lysates (ValloVax™) are used as a source of antigen for vaccinating against proliferating tumor endothelial cells in tumors.

Examples:

StemVacs-V Reduces 4T1 Tumor Growth After Intravenous Administration

svv-4t1-1.png
svv-4t1-1.png (146.98 KiB) Viewed 462 times
Cultured 4T1 cells were administered into the mammary fat pads of BALB/c mice at a concentration of 100,000 cells per mouse. When tumors reached a diameter of 5 mm, mice were administered control (saline) (diamond), 500,000 iPSC cells (square), or 500,000 StemVacs with no interferon pretreatment (triangle), or 500,000 cells with interferon pretreatment (“X”), intravenously once per week for three weeks. Tumors were excised and weighed at day 30 (n=11).


StemVacs-V Reduces 4T1 Tumor Growth After Intradermal Administration

svv-4t1-2.png
svv-4t1-2.png (221.99 KiB) Viewed 462 times
Cultured 4T1 cells were administered into the mammary fat pads of BALB/c mice at a concentration of 100,000 cells per mouse. When tumors reached a diameter of 5 mm, mice were administered control (saline) (diamond), 500,000 iPSC cells (square), or 500,000 StemVacs with no interferon pretreatment (triangle), or 500,000 cells with interferon pretreatment (“X”), intradermally once per week for three weeks. Tumors were excised and weighed at day 30 (n= 11).

References:

1. Carmeliet, P. and R.K. Jain, Angiogenesis in cancer and other diseases. Nature, 2000. 407(6801): p. 249-57.
2. Folkman, J., The role of angiogenesis in tumor growth. Semin Cancer Biol, 1992. 3(2): p. 65-71.
3. Meng, M.B., et al., Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: experimental and clinical evidence. Radiother Oncol, 2013. 106(1): p. 130-7.
4. Czarnota, G.J., et al., Tumor radiation response enhancement by acoustical stimulation of the vasculature. Proc Natl Acad Sci U S A, 2012. 109(30): p. E2033-41.
5. Peng, F., et al., Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models. PLoS One, 2012. 7(4): p. e34646.
6. Zawaski, J.A., et al., Effects of irradiation on brain vasculature using an in situ tumor model. Int J Radiat Oncol Biol Phys, 2012. 82(3): p. 1075-82.
7. Truman, J.P., et al., Endothelial membrane remodeling is obligate for anti-angiogenic radiosensitization during tumor radiosurgery. PLoS One, 2010. 5(9).
8. Stockmann, C., et al., The impact of the immune system on tumor: angiogenesis and vascular remodeling. Front Oncol, 2014. 4: p. 69.
9. Hirst, D.G., J. Denekamp, and B. Hobson, Proliferation kinetics of endothelial and tumour cells in three mouse mammary carcinomas. Cell Tissue Kinet, 1982. 15(3): p. 251-61.
10. Denekamp, J. and B. Hobson, Endothelial-cell proliferation in experimental tumours. Br J Cancer, 1982. 46(5): p. 711-20.
11. Hobson, B. and J. Denekamp, Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br J Cancer, 1984. 49(4): p. 405-13.
12. Folkman, J., Tumor angiogenesis: therapeutic implications. N Engl J Med, 1971. 285(21): p. 1182-6.
13. Folkman, J., Fighting cancer by attacking its blood supply. Sci Am, 1996. 275(3): p. 150-4.
14. Ellis, L.M. and I.J. Fidler, Finding the tumor copycat. Therapy fails, patients don't. Nat Med, 2010. 16(9): p. 974-5.
“And the corner sign says it's closing time so I'll bid farewell and be down the road...”
curncman
Posts: 564
Joined: Sat Mar 19, 2022 10:10 am

Re: Breast Cancer Treatment with STEMVACS-V-iPSC-TEC +Nanostilbene

Post by curncman »

Thanks Tim for your outstanding preview of what STEMVACS-V-iPSC-TEC could offer to suffering Breast Cancer patients worldwide. I wish your team efforts in bringing this treatment to the patient BEDSIDE is not far away and in that process many pharma Cos are ready to come forward to partner with TSOI to make STEMVACS-V-iPSC-TEC available to all breast cancer patients worldwide!
I am well wisher of everyone! GOD will pardon all your sins but not your Central Nervous System! Think Positive!
User avatar
Codycrusher
Posts: 730
Joined: Sat Mar 19, 2022 7:51 am

Re: Breast Cancer Treatment with STEMVACS-V-iPSC-TEC +Nanostilbene

Post by Codycrusher »

If it’s a successful treatment that knowing how TSOI rolls, it probably will be extremely successful, I don’t even think pharma would want to partner with TSOI, pharma are greedy, they will probably just make a huge buyout offer and be like, I want ownership of this and us pharma will complete it ourselves, they’re greedy and they like the valuable things for themselves.
Post Reply