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

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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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We love to see the science community solve this not uncle sam.
curncman
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Prophylactic immunization with Bubble liposomes and ultrasound-treated dendritic cells provided a four-fold decrease in

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Prophylactic immunization with Bubble liposomes and ultrasound-treated dendritic cells provided a four-fold decrease in the frequency of melanoma lung metastasis

https://www.sciencedirect.com/science/a ... 5911011059

Abstract
Melanoma has an early tendency to metastasize, and the majority of the resulting deaths are caused by metastatic melanoma. It is therefore important to develop effective therapies for metastasis. Dendritic cell (DC)-based cancer immunotherapy has been proposed as an effective therapeutic strategy for metastasis and recurrence due to prime tumor-specific cytotoxic T lymphocytes. In this therapy, it is important that DCs present peptides derived from tumor-associated antigens on MHC class I molecules. Previously, we developed an innovative approach capable of directly delivering exogenous antigens into the cytosol of DCs using perfluoropropane gas-entrapping liposomes (Bubble liposomes, BLs) and ultrasound. In the present study, we investigated the prevention of melanoma lung metastasis via DC-based immunotherapy. Specifically, antigens were extracted from melanoma cells and used to treat DCs by BL and ultrasound. Delivery into the DCs by this route did not require the endocytic pathway. The delivery efficiency was approximately 74.1%. DCs treated with melanoma-derived antigens were assessed for in vivo efficacy in a mouse model of lung metastasis. Prophylactic immunization with BL/ultrasound-treated DCs provided a four-fold decrease in the frequency of melanoma lung metastases. These in vitro and in vivo results demonstrate that the combination of BLs and ultrasound is a promising method for antigen delivery system into DCs.
curncman
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Lineage Cell COVID-19 vaccine Lineage Cell Therapeutics Leveraging Dendritic Cell Therapy Program for COVID-19 Vaccine D

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Lineage Cell COVID-19 vaccine
Lineage Cell Therapeutics Leveraging Dendritic Cell Therapy Program for COVID-19 Vaccine Development

Lineage Cell Therapeutics to apply allogeneic dendritic cell therapy programme to Covid-19 vaccine development
https://www.pharmaceutical-business-rev ... ward%20the

Lineage Cell Therapeutics, a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, announced that it has applied for grant funding from the California Institute for Regenerative Medicine (CIRM) to support the use of VAC, Lineage’s allogeneic dendritic cell therapy, toward the development of a potential vaccine against SARS-CoV-2, the virus which causes COVID-19.

In response to the COVID-19 pandemic, CIRM recently approved emergency funding and the allocation of $5 million for peer-reviewed regenerative medicine and stem cell research that could quickly advance treatments for COVID-19. The funding would be awarded as part of an expedited approval process.

“Several lines of clinical evidence encouraged us to apply the use of the VAC technology to the development of a prophylactic vaccine against SARS-CoV-2 and other coronaviruses,” stated Brian M. Culley, Lineage CEO.

“Recent publications have reported that patients infected with coronaviruses can exhibit modest neutralizing antibody titers and diminished T cell responses, suggesting it may be difficult for traditional vaccine approaches to generate long-term protection via the cellular immune response. Our belief is that dendritic cells, the body’s most potent antigen-presenting cell, can present viral antigens to the immune system to prime a robust immunological memory and provide durable, multi-year protection against the severe consequences of infection. This would be especially beneficial for front-line healthcare workers and others at risk of repeated exposure. Clinical data in patients with various cancers collected by Duke University Medical Center in early clinical trials of VAC1, the first product candidate from the VAC platform, showed nearly all patients developed evidence of antigen-specific T cell immune responses. This signal was confirmed in a majority of patients enrolled in a subsequent phase 2 study of VAC1 reported in 2016 by Asterias Biotherapeutics, which Lineage acquired in 2019. We believe these and additional data provide validation of the underlying mechanism of using dendritic cells to present antigens to the body’s immune system. We believe we are unique among cell therapy companies that are evaluating solutions to the COVID-19 pandemic because we are not focused on late-stage critical care, but on providing long-term prophylactic protection against infection, which may help reduce the need for hospitalization and address a critical gap among the critical care and humoral immunity approaches currently in development. The ideal scenario is that protection against COVID-19 in high-risk individuals would become durable, similar to measles or pertussis, rather than influenza, which requires an annual vaccination.”

Mr. Culley continued, “Presenting a viral antigen by means of our allogeneic dendritic cell platform will require manufacturing process development and creating a new expression construct prior to submitting an Investigational New Drug (IND) application to enable clinical evaluation. This will entail a modest investment of capital, but we feel that we are able to manage this new program alongside our existing programs in dry AMD and spinal cord injury. We recently raised $3.8M of cash from the sale of OncoCyte shares and this capital, alongside the translational research grant application submitted to CIRM, should it be approved, will help support our work in this area. We also intend to seek additional opportunities to obtain non-dilutive backing for this program.”

VAC is an allogeneic, or non-patient specific, product candidate platform designed to stimulate patient immune responses to antigens commonly expressed in cancerous cells but not in normal adult cells. VAC product candidates are produced from a pluripotent cell line using a directed differentiation method and are comprised of a population of nonproliferating mature dendritic cells. As the most potent type of antigen presenting cell in the body, dendritic cells instruct our body’s immune system to attack and eliminate harmful pathogens and unwanted cells. Because the antigen is loaded exogenously into the dendritic cells prior to administration, VAC is a platform technology that can be modified to carry any antigen, including patient-specific tumor neo-antigens or viral antigens. An earlier VAC program, called VAC1, was comprised of autologous dendritic cells and provided proof-of-concept for VAC2, an allogeneic product candidate.

With $3 billion in funding and approximately 300 active stem cell programs in its portfolio, CIRM is the world’s largest institution dedicated to helping people by bringing the future of cellular medicine closer to reality. In response to the crisis caused by the COVID-19 virus, CIRM recently approved emergency funding and the allocation of $5 million for peer-reviewed regenerative medicine and stem cell research that could quickly advance treatments for COVID-19. The funding would be awarded as part of an expedited approval process.
curncman
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STEMVACS2

Post by curncman »

A I understand STEMVACS 2 is loading dendritic cells with protiens expressed in cancer cells, to get our immune system super charged to attack COVID-19.
STEMVACS2 is an allogeneic, or non-patient specific, COVD-19 vaccine candidate designed to stimulate patient immune responses against COVID-19. STEMVACS2, which is produced from our pluripotent cell technology using a directed differentiation method, is comprised of a population of mature dendritic cells. As the most potent type of antigen presenting cell in the body, dendritic cells instruct our body’s immune system to attack and eliminate harmful pathogens and unwanted cells. Because the tumor antigen is loaded exogenously into the dendritic cells prior to administration, STEMVACS2 is a platform technology that can be modified to carry any antigen, including patient-specific tumor neo-antigens.
curncman
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Joined: Fri Jun 26, 2020 8:27 am

STEMVACS2

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COVID-19, which afflicts millions worldwide, is one the largest unmet clinical needs with current treatment options providing limited efficacy and a wide range of debilitating side effects. The use of pluripotent cells as the starting material for STEMVACS2 production adds several additional advantages to this candidate therapeutic. In comparison to autologous technologies that rely on the use of a patient’s own blood, TSOI's allogeneic STEMVACS2 is pluripotent cell technology provides a scalable system for production of a large number of vaccine doses in a single lot, lower manufacturing costs, greater product consistency, and off-the-shelf availability to provide broader access to patients. In addition, we believe that as an allogeneic therapy, STEMVACS2 has the potential to stimulate a more robust immune response through an adjuvant effect resulting from the partial immune mismatch between the STEMVACS2 cells and patients receiving the therapy.
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

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

Post by curncman »

Tim, Can u please when we can expect to have the preclinical and pilot human trial for COVID 19 treatment completed and paper published on STEMVACS 2? TiA

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.”
curncman
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Effects of decitabine on allogeneic immune reactions of donor lymphocyte infusion via activation of dendritic cells

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Effects of decitabine on allogeneic immune reactions of donor lymphocyte infusion via activation of dendritic cells
Research
Open Access
Published: 03 September 2020
https://ehoonline.biomedcentral.com/art ... 20-00178-y

Abstract
Background
Successful prevention of post-transplantation relapse after donor lymphocyte infusion (DLI) depends on its capability to mediate an effective graft-versus-leukemia (GVL) response while minimizing DLI-related toxicity, including graft-versus-host disease (GVHD).

Methods
We assessed the effects of decitabine (DEC), a hypomethylating agent, upon allogeneic immune reaction in a murine model of DLI.

Results
Significantly greater tumor growth retardation and survival prolongation occurred in mice administered with 1.0 mg/kg DEC for 5 days (DEC-1.0) than in control or DEC-0.1 mice. Upon prompt DEC and DLI co-administration, dendritic cells (DCs) were activated; DEC-1.0/DLI induced severe GVHD, and survival was significantly lower than with DLI alone or DEC-0.1/DLI treatments. IFN-γ and CD28 levels were higher in splenic DCs of DEC-1.0 mice than in those of control mice. Assessment of delayed DLI co-administration with DEC, when IFN-γ levels were normalized to control levels, revealed that DEC-1.0/DLI successfully facilitated tumor management without causing severe GVHD.

Conclusions
Our results suggest that DEC primes allogeneic immune reactions of DLI via DC activation, and GVHD and GVL effects are separable through optimal DLI timing based on DEC-induced increase in IFN-γ expression levels.
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

Immunomic Therapeutics Announces Publication of Results from 3 ATTAC Studies of CMV-Specific Dendritic Cell Vaccines for

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Immunomic Therapeutics Announces Publication of Results from 3 ATTAC Studies of CMV-Specific Dendritic Cell Vaccines for the Treatment of GBM

https://www.firstwordpharma.com/node/1753894

~25-35 % survival over 5 years from diagnosis in vaccinated GBM patients vs a historical rate of ~ 5%

ROCKVILLE, Md. & SAN DIEGO--(BUSINESS WIRE)-- Immunomic Therapeutics, Inc., ("ITI"), a privately-held clinical-stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, announced today that results from multiple ATTAC clinical studies of dendritic cell vaccines have been published online by American Association for Cancer Research (AACR) in an article titled, "Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma."

ITI is developing several dendritic cell vaccines for the treatment of cancer, including ITI-1000 for glioblastoma (GBM), with leaders in cancer immunotherapy for brain tumors, John Sampson, M.D., Ph.D. from Duke University and Duane Mitchell, M.D., Ph.D. from the University of Florida. ITI's dendritic cell vaccine is designed to target the pp65 viral antigen of Cytomegalovirus (CMV) that is expressed in GBM, but not in normal brain cells.

In the ATTAC studies, the GBM patients' white blood cells are removed, matured into dendritic cells (DCs), and modified to generate a vaccine to the pp65 viral protein when fused to the LAMP1 protein for antigen presentation. This DC vaccine is then returned to the patient. As observed in the ATTAC studies, ITI believes this approach may harness the body's immune system to recognize, attack and destroy tumor cells that express CMV in GBM and potentially other cancers. The published results from the three original ATTAC clinical studies are summarized below:

Three separate clinical trials conducted by Drs. Mitchell and Sampson utilized Cytomegalovirus specific dendritic cell vaccines in patients with newly diagnosed glioblastoma.

The three small studies (total n = 26; NCT#s 00639639, 2366728) revealed that overall 5-year survival increased from a historical low of 5% to 25%. However, in two of the studies, vaccination site pre-conditioning with either Td or GM-CSF:

Enhanced the immune response by increasing migration of DCs to regional lymph nodes to "present" the pp65 CMV antigen to immune cells.
Increased the percentage of long-term, 5-year survivors to nearly 35% in that subset of treated patients who received vaccination site pre-conditioning with either Td or GM-CSF.
This data is preliminary, and additional studies are needed.

"These study results not only advance our understanding of a virus' role in cancer, but they also signal tremendous hope to patients and their families suffering from this devastating disease," Sampson said. "I look forward to continued evaluation of ITI's dendritic cell vaccines, including ITI-1000, in the ongoing, randomized, placebo-controlled ATTAC-II study."

"GBM is the most aggressive form of brain cancer, often resulting in a patient's death within one to two years from diagnosis. Historically, it is a very difficult disease to treat and current treatment options offer limited benefit to extend survival," added Mitchell. "The results demonstrated with CMV-specific dendritic vaccines in the ATTAC studies are very encouraging, particularly in the observation of a significant fraction of long-term survivors and favorable safety profile of the vaccine platform. We remain steadfast in our pursuit to identify effective treatments for patients with GBM and look forward to the continued evaluation of ITI's vaccines in addressing this clear and pressing unmet medical need."

The AACR article can be found here.

About Glioblastoma (GBM)

According to the American Association of Neurological Surgeons, GBM is an aggressive brain cancer that often results in death within 15 months of diagnosis. GBM develops from glial cells (astrocytes and oligodendrocytes), grows rapidly, and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents about 15% of all primary brain tumors and approximately 10,000 cases of GBM are diagnosed each year in the U.S.

About ITI-1000 and the Phase 2 (ATTAC-II) Study

ITI-1000 is an investigational dendritic cell vaccine therapy currently in a Phase 2 clinical trial (ATTAC-II) for the treatment of GBM. ITI-1000 was developed using Immunomic's proprietary investigational lysosomal targeting technology, UNITE, in the context of cell therapy. In May 2017, Immunomic exclusively licensed a patent portfolio from Annias Immunotherapeutics for use in combination with UNITE and ITI-1000, allowing Immunomic to combine UNITE with a patented and proprietary CMV immunotherapy platform. The ATTAC-II study (NCT02465268) is a Phase II randomized, placebo-controlled clinical trial enrolling patients with newly diagnosed GBM that will explore whether dendritic cell (DC) vaccines, including ITI-1000, targeting the CMV antigen pp65 improves survival. This study is enrolling up to 120 subjects at 3 clinical sites in the United States. For more information on the ATTAC-II study, please visit www.clinicaltrials.gov.
curncman
Posts: 496
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Genetic models of human and mouse dendritic cell development and function

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Genetic models of human and mouse dendritic cell development and function

https://www.nature.com/articles/s41577-020-00413-x
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-e

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The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model

https://link.springer.com/article/10.10 ... 20-02117-0
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