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After seeing that fostemsavir could reduce signs of chronic inflammation in HIV-infected cells, the researchers are launching a clinical trial to see if the drug benefits HIV patients when added to their ART regimen. Antiretroviral therapy, or ART, has made it possible for HIV-positive people to live just as long as those without the virus. But though their lifespans may be equal, healthspans are another matter: People with HIV start experiencing chronic health problems, like liver and heart disease, an average of 16 years earlier than their HIV-negative peers.  Researchers have linked this gap to ongoing inflammation, which persists even when ART has suppressed the virus to undetectable levels. Now, new findings from researchers at the University of Montreal Hospital Research Centre suggest that a protein called gp120 might be a key culprit. They concluded that there is a case for using the gp120-inhibiting ART drug fostemsavir—marketed as Rukobia by GSK's subsidiary ViiV—beyond its indication for patients with multi-drug resistant HIV.  Gp120 is found on the outer surface of HIV, which uses it to infect immune cells. The new study shows its presence may also contribute to chronic inflammation as well as mild heart disease and immune dysfunction. When the researchers measured gp120 levels in the plasma of 347 male and 39 female patients with HIV, all of whom had an undetectable viral load, they found that it was elevated in a third of them. Those patients were more likely to also have higher levels of inflammatory cytokines and low-grade coronary artery disease.  “We’re showing that [gp120] acts as a toxin and is associated [with] chronic inflammation leading to comorbidities,” study lead Andrés Finzi, Ph.D., said in a press release.  Given that fostemsavir works by inhibiting gp120, the researchers conducted studies on HIV-infected cells to see if it could reduce biomarkers related to chronic inflammation. The results were positive enough to convince three Canadian health organizations, including the Canadian Institutes of Health Research, to fund a two-year clinical trial to see if the drug could stave off inflammation-linked comorbidities in patients when added to their existing ART treatments.  "If our trial proves to be conclusive, there would be a paradigm shift in current treatment," Madeleine Durand, M.D., a senior author of the study and scientist at the University of Montreal research center, said in the press release. Personalizing ART regimens to add fostemsavir in patients with elevated gp120 levels "could relieve the burden of their comorbidities and improve their quality of life," she added.  The trial will start in 2024 and will measure the progression of atherosclerosis along with changes in frailty and cognition, the press release said. It will include around 200 people; the researchers aim for half of them to be women.

Recent $11.3 million grant from the California Institute for Regenerative Medicine (CIRM) intended to fund the Phase 1 clinical trial at City of Hope; the Investigational New Drug application for which has now been accepted by the Food and Drug Administration In preclinical studies, administration of the dual-action CAR T cells followed by administration of a CMV vaccine successfully eradicated HIV, including from latent reservoirs Triplex is currently the subject of multiple ongoing clinical trials, including: a Phase 1/2 trial for CMV control in pediatric recipients of HCT (see NCT03354728); a Phase 2 trial for reduction in viral load of Human Immunodeficiency Virus (“HIV”) in adults co-infected with HIV and CMV (see NCT05099965); and a Phase 1 trial of Triplex in combination with a bi-specific CMV/CD19 Chimeric Antigen Receptor T Cell for the treatment of Non-Hodgkin Lymphoma (see NCT05432635); Other planned studies of Triplex include: a multicenter Phase 2 trial for CMV control in recipients of liver transplant (U01AI163090, see NCT06075745); a Phase 2 trial for CMV control in recipients of kidney transplant; and a Phase 2 trial for CMV control in recipients of stem cell transplant in which the stem cell donor is vaccinated with Triplex (see NCT06059391) Helocyte, Inc. (“Helocyte”), a subsidiary company of Fortress Biotech, Inc. (“Fortress”) (Nasdaq: FBIO), today announced that it executed an exclusive option agreement with City of Hope for patent rights to use Triplex, a cytomegalovirus vaccine, in combination with cytomegalovirus (“CMV”)-specific, Anti-Human Immunodeficiency Virus (“HIV”) Chimeric Antigen Receptor (“CAR”) (collectively, CMV/HIV-CAR) T Cells for the treatment of adults living with HIV. Triplex was initially developed by City of Hope, one of the largest cancer research and treatment organizations in the United States, and exclusively licensed to Helocyte in 2015. Additionally, the California Institute for Regenerative Medicine (“CIRM”) recently awarded a $11.3 million grant to City of Hope to fund a Phase 1 clinical trial. The Phase 1 trial is expected to enroll up to 12 healthy individuals living with HIV-1 on stable anti-retroviral therapy (“ART”) who have maintained viral suppression for at least 48 weeks. The study will include three dose-escalating cohorts, along with an expansion cohort. Other cohorts will include further vaccination of subjects with Triplex to drive continued proliferation of the CAR. The trial will initially enroll at City of Hope and University of California at San Diego. “City of Hope made a major advancement when our transplant team helped a patient achieve remission for both HIV and leukemia,” said John A. Zaia, M.D., the Aaron D. Miller and Edith Miller Chair for Gene Therapy at City of Hope. “We are hoping to evaluate a CAR T therapy for HIV in a Phase 1 clinical trial so that one day more people with HIV might be able to achieve long-term HIV remission.” The clinical study will build upon preclinical data published in Molecular Therapy - Methods & Clinical Development which demonstrated the potential efficacy of combining a CMV vaccine and CMV/HIV CAR T cell therapy to eradicate HIV. The study illustrated the potential long-term durability of the combination therapy, which induced therapeutic immune cells to take hold in bone marrow. The objective of this approach is to target and eradicate latent viral T cell reservoirs in immune cells to achieve complete HIV clearance. The current standard of care for the treatment of HIV relies upon the use of ART, which is a non-curative, life-long therapy. Optimal use of ART can effectively control HIV replication; prevent the onset of Acquired Immuno-Deficiency Syndrome (“AIDS”); prolong survival; and reduce the risk of transmission to others. However, there are several challenges associated with the use of ART, including: chronic treatment adherence; drug resistance, particularly in those who do not fully adhere to treatment; adverse events; and the persistence of immune dysfunction during treatment. There remains a significant unmet medical need to provide a functional cure for HIV and eliminate the need for ART. To date, the engineering of T cells to express HIV-specific CAR T cells has failed to demonstrate meaningful clinical benefits. This is believed to be due in part to the effectiveness of highly active ART, which reduces HIV viral load to a level that prevents the activation of CAR T cells. The use of Triplex is believed to stimulate CMV/HIV-CAR T cells to proliferate within patients’ bodies. In the aforementioned preclinical study, CAR T cells were engineered to target and kill cells tagged with a particular protein called gp120, which is expressed in all HIV viruses, frequently with mutations that cause the virus to evade natural immunity without affecting healthy cells. Lindsay A. Rosenwald, M.D., Fortress’ Chairman and Chief Executive Officer and Chairman of Helocyte, Inc., said, “Our goal is to deliver transformational treatment options to patients suffering from conditions associated with high unmet medical need. We are pleased to expand our relationship with City of Hope and remain encouraged by the potential to combine Helocyte’s Triplex with a bispecific CMV/HIV-CAR T cell therapy that can eradicate HIV without safety issues. We look forward to building upon the data that continue to be generated relating to the use of Triplex in the treatment of HIV, including an ongoing Phase 2 clinical trial evaluating the safety and efficacy of Triplex in eliciting a CMV-specific immune response and reducing CMV replication in adults co-infected with HIV and CMV. Triplex is the subject of multiple other ongoing and planned studies.” The California Institute for Regenerative Medicine was created in 2004 after 59% of California voters approved California Proposition 71: the Research and Cures Initiative, which allocated $3 billion to fund stem cell research in California. For additional information regarding the grant, please see https://www.cirm.ca.gov/our-progress/awards/evaluation-safety-and-feasibility-cytomegalovirus-specific-anti-hiv-chimeric-antigen-receptor-cmv-hiv-car-t-cells-people-hiv/. About Triplex Triplex is a universal (non-HLA-restricted) recombinant Modified Vaccinia Ankara viral vector vaccine engineered to induce a robust and durable virus-specific T cell response to three immuno-dominant proteins [UL83 (pp65), UL123 (IE1), UL122 (IE2)] linked to CMV complications in the post-transplant setting. In previous Phase 1 and Phase 2 studies, Triplex was found to be safe, well-tolerated and highly immunogenic. Triplex is currently the subject of multiple ongoing clinical trials, including: a Phase 1/2 trial for CMV control in pediatric recipients of HCT (see NCT03354728); a Phase 2 trial for reduction in viral load of Human Immunodeficiency Virus (“HIV”) in adults co-infected with HIV and CMV (see NCT05099965); and a Phase 1 trial of Triplex in combination with a bi-specific CMV/CD-19 Chimeric Antigen Receptor T Cell for the treatment of Non-Hodgkin Lymphoma (see NCT05432635). Triplex is also the subject of several planned studies, including: a Phase 2 evaluation for CMV control in recipients of liver transplant (see NCT06075745); a Phase 2 trial for CMV control in recipients of kidney transplant; and a Phase 2 trial for CMV control in recipients of stem cell transplant in which the stem cell donor is vaccinated with Triplex (see NCT06059391). About Helocyte Helocyte is a clinical-stage company developing novel immunotherapies for the prevention and treatment of cancer and infectious disease (and in particular, cytomegalovirus or “CMV”). The Centers for Disease Control estimate that 50 to 80 percent of Americans are infected with CMV by the age of 40. While the virus is asymptomatic in healthy individuals, it can cause severe and life-threatening disease in those with weakened or uneducated immune systems. Patients undergoing allogeneic stem cell and solid organ transplantation are at particularly high risk of experiencing complications associated with CMV. According to the Center for International Blood and Marrow Transplant Research, there were over 9,000 unrelated and related bone marrow and cord blood transplants performed in the United States in 2020. According to preliminary data from the Organ Procurement and Transplantation Network, there were over 40,000 organ transplants performed in the United States in 2021, comprised primarily of kidney and liver transplant procedures. Helocyte’s Triplex vaccine is engineered to induce a robust and durable virus-specific T cell response to control CMV in transplant recipients. While current antiviral therapies have reduced the rate of CMV disease-related mortality in transplant recipients, such treatments have been linked to increased toxicity, delayed immune reconstitution and late onset of CMV. The Helocyte vaccines can educate the body’s innate immune system to fight CMV. For more information, please visit www.helocyte.com. About Fortress Biotech Fortress Biotech, Inc. (“Fortress”) is an innovative biopharmaceutical company focused on acquiring, developing and commercializing high-potential marketed and development-stage drugs and drug candidates. The company has eight marketed prescription pharmaceutical products and over 25 programs in development at Fortress, at its majority-owned and majority-controlled partners and subsidiaries and at partners and subsidiaries it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is focused on leveraging its significant biopharmaceutical industry expertise and network to further expand the company’s portfolio of product opportunities. Fortress has established partnerships with some of the world’s leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including AstraZeneca plc, City of Hope, Fred Hutchinson Cancer Center, St. Jude Children’s Research Hospital, Nationwide Children’s Hospital and Sentynl Therapeutics, Inc. For more information, visit www.fortressbiotech.com. The content above comes from the network. if any infringement, please contact us to modify.

The CIRM funds will support cell and gene therapy clinical trials for HIV, leukemia and a bone marrow disease LOS ANGELES, Aug. 9, 2023 /PRNewswire/ -- Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States and a leading research center for diabetes and other life-threatening illnesses, were awarded $32.3 million from the California Institute for Regenerative Medicine (CIRM) to support three novel Phase 1 clinical trials evaluating innovative cell and gene therapy treatments for patients with HIV, acute myeloid leukemia and severe aplastic anemia. Continue Reading Researchers at City of Hope were awarded $32.3 million from the California Institute for Regenerative Medicine (CIRM) to support three novel Phase 1 clinical trials evaluating innovative cell and gene therapy treatments for patients with HIV, acute myeloid leukemia and severe aplastic anemia. (Photo credit: City of Hope) Beckman Research Institute of City of Hope was awarded two-thirds of the $50 million in this latest round of CIRM awards, the highest of any entity in the state. "These CIRM awards are a testament to City of Hope's commitment to the advancement of gene therapies for the treatment of human diseases," said John D. Carpten, Ph.D., City of Hope's chief scientific officer, Irell & Manella Cancer Center Director's Distinguished Chair and Morgan & Helen Chu Director's Chair of the Beckman Research Institute. "Through our tireless pursuit of best-in-class research and innovation, we believe our work at City of Hope will benefit patients living with HIV or impacted by cancer, and we thank CIRM for its support to help make this a reality." City of Hope is a leader in gene therapies, including bone marrow and blood stem cells transplants. As one of the highest volume transplant centers in the nation and the largest in California, more than 18,000 transplants have been performed at City of Hope since it became one of the first cancer centers in the U.S. to perform the therapy in 1976. City of Hope and other institutions also developed a pretransplant treatment for older adults and other patients that resulted in the fifth patient in the world — and the oldest — to achieve long-term remission for leukemia and HIV. (The patient had also received stem cells from a donor with a rare genetic mutation that makes people resistant to most HIV strains.) Potential bispecific CAR T therapy for HIV City of Hope is at the forefront of another cellular therapy known as chimeric antigen receptor therapy (CAR) T cell therapy, which uses a patient's own immune system to fight cancer and has the potential to target other diseases, such as HIV. More than 80 CAR T and other immune effector cell trials have been conducted to date at City of Hope and over 1,200 patients have been treated with CAR T therapy, either in clinical trials, which may use CARs developed by City or Hope, or Food & Drug Administration-approved CAR T cell therapies. "City of Hope made a major advancement when our transplant team helped Paul Edmonds, globally known as the 'City of Hope patient,' go into remission for both HIV and leukemia," said John A. Zaia, M.D., the Aaron D. Miller and Edith Miller Chair for Gene Therapy at City of Hope. "We are hoping to evaluate a CAR T therapy for HIV in a Phase 1 clinical trial so that one day more people with HIV might be able to achieve long-term HIV remission." CIRM awarded Zaia $11.3 million for the clinical trial. Up to 12 healthy people with HIV will be treated in this first-in-human study performed at City of Hope and the University of California San Diego. The investigators include John Baird, M.D., Angelo Cardoso, M.D., Ph.D., Joycelynne Palmer, Ph.D., and Xiuli Wang, Ph.D., at City of Hope and colleagues at UCSD. Zaia's team will test a novel approach City of Hope scientists developed where a patient's immune T cells are engineered to target both the HIV antigen gp120 and a common virus that infects nearly all persons living with HIV, namely cytomegalovirus. The researchers' aim is for these bispecific HIV-CAR T cells to persist and eliminate HIV-infected cells so that antiviral drugs are no longer needed. Trial to focus on a difficult blood cancer to treat CIRM awarded a City of Hope team led by Elizabeth Budde, M.D., Ph.D., nearly $12 million to develop and conduct a first-in-human Phase 1 immunotherapy trial for acute myeloid leukemia (AML), which has the highest mortality rate of all blood cancers. "It is critical to find more effective therapies for patients whose AML has relapsed," said Budde, a City of Hope associate professor in the Department of Hematology & Hematopoietic Cell Transplantation. "We are hopeful that this novel therapy will eventually enable City of Hope and other institutions to offer a new treatment for patients whose AML has returned. We are very grateful for the recognition and support from CIRM." Most AML patients who go into remission after one treatment will develop the disease again and will then need a blood stem cell transplant from a donor. Even after a transplant, patients can still relapse, leaving them with few treatment options. The CIRM-funded trial will be the first to use T cells, a type of immune cell, from a healthy donor who has donated stem cells for the AML patient to undergo a transplant. These cells will be reengineered in a laboratory to express CD33CARs, or special receptors on a cell's surface. These CARs will target the CD33 protein, which is found in more than 80% of AML cases. T cells harboring the CD33CARs will also be multiplied to millions and then infused back into the patient. The CARs are living cells and expected to multiply inside a patient's body and recognize and kill the cancer cells. Before receiving the CAR T cell therapy, patients will receive chemotherapy to prepare their bodies to accept the CAR T cells. The trial, which will enroll up to 18 AML patients who have relapsed after receiving a transplant, will evaluate the CAR T therapy's safety and its effectiveness in eliminating leukemia cells. City of Hope's David Horne, Ph.D., Marissa Del Real, Ph.D., Karam Sandhu, M.D., and Anthony Stein, M.D., are co-investigators on this project. Finding a better treatment for severe aplastic anemia A City of Hope research team received $9.05 million from CIRM to start a clinical trial using a novel blood stem cell transplantation procedure for severe aplastic anemia, a rare bone marrow disease that can turn into blood cancer and is currently difficult to treat. If successful, the treatment could also be used for other autoimmune diseases, such as treatment-resistant type 1 diabetes. Currently, a blood stem cell transplant from a related or unrelated donor whose human leukocyte antigen (HLA) genes match a patient's HLA is the most effective treatment for severe aplastic anemia. But it is difficult to find unrelated donor matches for people of color due to a limited number of donors from various racial and ethnic groups. Transplants can also cause severe side effects, particularly in older patients. Defu Zeng, Ph.D., a City of Hope professor with the Department of Immunology & Theranostics within the Arthur Riggs Diabetes & Metabolism Research Institute, has led research on the potential new therapy, which involves induction of mixed chimerism in adult patients. Mixed chimerism refers to transplanting blood-forming stem cells from a healthy, half-matched family member donor into a patient who has received a milder, less toxic chemotherapy treatment free of radiation that removes some, but not all, of the patient's diseased bone marrow stem cells. The Phase 1 trial is expected to start later this year and will enroll up to six patients. "City of Hope has extensive expertise performing bone marrow and stem cell transplants for patients with blood cancers and other diseases, and we are consistently looking for ways to improve the process and effectively treat more patients with transplants, regardless of any barriers," said Ryotaro Nakamura, City of Hope's Jan & Mace Siegel Professor in Hematology & Hematopoietic Cell Transplantation in the Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, and the trial's principal investigator. "We are hopeful that this will provide another treatment option for patients with this devastating disease and thankful for CIRM's funding." City of Hope has treated patients with sickle cell diseases using this novel therapy in a clinical trial also funded by CIRM. About City of Hope City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago and Phoenix. City of Hope's affiliated group of organizations includes Translational Genomics Research Institute and AccessHope™. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn. SOURCE City Of Hope