Background:
During a transplant, blood stem cells from one person are given to someone else. The cells grow into the different cells that make up the immune system. This can cure people with certain immunodeficiencies. But transplant has many risks and complications.
Objective:
To see if stem cell transplant can be successfully performed in people with primary immunodeficiency disease and cure them.
Eligibility:
People ages 4-69 for whom a primary immunodeficiency (PID) or Primary Immune Regulatory Disorder (PIRD), has caused significant health problems and either standard management has not worked or there are no standard management options, along with their donors
Design:
Donors will be screened under protocol 01-C-0129. They will donate blood or bone marrow.
Participants will be screened with:
Medical history
Physical exam
Blood, urine, and heart tests
CT or PET scans
Before transplant, participants will have dental and eye exams. They will have a bone marrow biopsy. For this, a needle will be inserted through the skin into the pelvis to remove marrow.
Participants will be hospitalized before their transplant. They will have a central catheter put into a vein in their chest or neck. They will get medications through the catheter to prevent complications. Participants will get stem cells through the catheter. They will stay in the hospital for at least 4 weeks. They will give blood, urine, bone marrow, and stool samples. They may need blood transfusions. They may need more scans. They will take more medications.
Participants will have visits on days 30, 60, 100, 180, and 360, and 24 months after the transplant. Then they will have visits once a year for about 5 years

Start Date22 Sep 2020

Sponsor / Collaborator

National Cancer Institute

NCT03663933 / RecruitingPhase 2IIT

Phase II Trial of Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation

Background:
Blood stem cells in the bone marrow make all the cells to normally defend a body against disease. Allogeneic blood or marrow transplant is when these stem cells are transferred from one person to another. Researchers think this treatment can provide a new, healthy immune system to correct T-cell problems in some people.
Objective:
To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with T-cell problems.
Eligibility:
Donors: Healthy people ages 4 and older
Recipients: People the same age with abnormal T-cell function causing health problems
Design:
All participants will be screened with:
Medical history
Physical exam
Blood, heart, and urine tests
Donors will also have an electrocardiogram and chest x-ray. They may have veins tested or a pre-anesthesia test.
Recipients will also have lung tests.
Some participants will have scans and/or bone marrow collected by needle in the hip bones.
Donors will learn about medicines and activities to avoid and repeat some screening tests.
Some donors will stay in the hospital overnight and have bone marrow collected with anesthesia.
Other donors will get shots for several days to stimulate cells. They will have blood removed by plastic tube (IV) in an arm vein. A machine will remove stem cells and return the rest of the blood to the other arm.
Recipients will have:
More bone marrow and a small fragment of bone removed
Dental, diet, and social worker consultations
Scans
Chemotherapy and antibody therapy for 2 weeks
Catheter inserted in a chest or neck vein to receive donor stem cells
A hospital stay for several weeks with more medicines and procedures
Multiple follow-up visits

Start Date04 Sep 2018

Sponsor / Collaborator

National Cancer Institute

NCT03188419 / CompletedNot ApplicableIIT

Retrospective Study of the Breadth of Donor Options for Patients With Inherited Diseases Requiring Allogeneic Hematopoietic Stem Cell Transplant in the Era of Alternative Donor Transplants Using Post-Transplantation Cyclophosphamide

Background:
People who have certain immune system diseases often need a procedure called allo HSCT. This is short for allogeneic hematopoietic stem cell transplant. This might cure people with these diseases. Many people who need allo HSCT need donors who are relatives with similar genes. But the disease may also affect those in the donor pool. This may mean there are fewer options for people with inherited diseases. Researchers want to collect data on how transplant candidates and their donors are found.
Objective:
To find out how genetic diseases and the ways they are inherited affect the breadth of options for allo HSCT donors.
Eligibility:
Records from studies that have already been done. These will be for people ages 4 and older who were evaluated for allo HSCT or to be donors.
Design:
Participants already signed a consent form for their records to be shared.
Researchers will study the participant data.
Data will be stored in an electronic system. Researchers will use passwords to protect the data.

Start Date14 Jun 2017

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with T Cell Immunodeficiency Primary

100 Translational Medicine associated with T Cell Immunodeficiency Primary

0 Patents (Medical) associated with T Cell Immunodeficiency Primary

366

Literatures (Medical) associated with T Cell Immunodeficiency Primary

08 Feb 2024·American journal of respiratory cell and molecular biology

Lung Interstitial Macrophages Can Present Soluble Antigens and Induce Foxp3+ Regulatory T Cells.

Article

Author: Céline Legrand ; Domien Vanneste ; Alexandre Hego ; Catherine Sabatel ; Kiréna Mollers ; Joey Schyns ; Pauline Maréchal ; Joan Abinet ; Amandine Tytgat ; Maude Liégeois ; Barbara Polese ; Margot Meunier ; Coraline Radermecker ; Laurence Fiévez ; Fabrice Bureau ; Thomas Marichal

Lung macrophages constitute a sophisticated surveillance and defense system that contributes to tissue homeostasis, host defense, and allows the host to cope with the myriad of insults and antigens to which the lung mucosa is exposed. As opposed to alveolar macrophages, lung interstitial macrophages express high levels of type 2 major histocompatibility complex (MHC-II), a hallmark of antigen-presenting cells. Here, we showed that lung IMs, like dendritic cells (DCs), possess the machinery to present soluble antigens in an MHC-II-restricted way. Using ex vivo ovalbumin (OVA)-specific T cell proliferation assays, we found that OVA-pulsed IMs could trigger OVA-specific CD4⁺ T cell proliferation and Foxp3 expression via MHC-II-, IL-10 and Tgfβ-dependent mechanisms. Moreover, we showed that IMs efficiently captured locally instilled antigens in vivo, did not migrate to the draining lymph nodes and enhanced local interactions with CD4⁺ T cells in a model of OVA-induced allergic asthma. These results support that IMs can present antigens to CD4⁺ T cells and trigger regulatory T cells, which might attenuate lung immune responses and have functional consequences for lung immunity and T-cell-mediated disorders.

05 Feb 2024·Communications biology

Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.

Article

Author: Evgeniya Petrova ; Jesús María López-Gay ; Matthias Fahrner ; Florent Leturcq ; Jean-Pierre de Villartay ; Claire Barbieux ; Patrick Gonschorek ; Lam C Tsoi ; Johann E Gudjonsson ; Oliver Schilling ; Alain Hovnanian

Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here we describe a novel and viable, Spink5 conditional knock-out (cKO) mouse model, allowing to study NS progression. By combining transcriptomics and proteomics, we determine a disease molecular profile common to mouse models and NS patients. Spink5 cKO mice and NS patients share skin barrier and inflammation signatures defined by up-regulation and increased activity of proteases, IL-17, IL-36, and IL-20 family cytokine signaling. Systemic inflammation in Spink5 cKO mice correlates with disease severity and is associated with thymic atrophy and enlargement of lymph nodes and spleen. This systemic inflammation phenotype is marked by neutrophils and IL-17/IL-22 signaling, does not involve primary T cell immunodeficiency and is independent of bacterial infection. By comparing skin transcriptomes and proteomes, we uncover several putative substrates of tissue kallikrein-related proteases (KLKs), demonstrating that KLKs can proteolytically regulate IL-36 pro-inflammatory cytokines. Our study thus provides a conserved molecular framework for NS and reveals a KLK/IL-36 signaling axis, adding new insights into the disease mechanisms and therapeutic targets.

11 Dec 2023·International journal of molecular sciences

CD147/Basigin Is Involved in the Development of Malignant Tumors and T-Cell-Mediated Immunological Disorders via Regulation of Glycolysis.

Review

Author: Takuro Kanekura

CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MTC-1 and MCT-4 export the lactic acid that is converted from pyruvate in glycolysis to maintain the intracellular pH level and a stable metabolic state. Under physiological conditions, cellular energy production is induced by mitochondrial oxidative phosphorylation. Glycolysis usually occurs under anaerobic conditions, whereas cancer cells depend on glycolysis under aerobic conditions. T cells also require glycolysis for differentiation, proliferation, and activation. Human malignant melanoma cells expressed higher levels of MCT-1 and MCT-4, co-localized with CD147 on the plasma membrane, and showed an increased glycolysis rate compared to normal human melanocytes. CD147 silencing by siRNA abrogated MCT-1 and MCT-4 membrane expression and disrupted glycolysis, inhibiting cancer cell activity. Furthermore, CD147 is involved in psoriasis. MCT-1 was absent on CD4⁺ T cells in CD147-deficient mice. The naïve CD4⁺ T cells from CD147-deficient mice exhibited a low capacity to differentiate into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in the CD147-deficient mice than in the wild-type mice. Overall, CD147/Basigin is involved in the development of malignant tumors and T-cell-mediated immunological disorders via glycolysis regulation.

News (Medical) associated with T Cell Immunodeficiency Primary

10 Dec 2022

·www.globenewswire.com

AltruBio Presents New Positive Data from its Completed Phase 1b Study Evaluating ALTB-168 in Patients with Steroid-Refractory or Treatment-Refractory Acute Graft-Versus-Host-Disease at the 64th ASH Annual Meeting 2022

-Participants with SR-aGVHD disease achieved an ORR of 67% and CR of 17% as measured by best response- -Participants with TR-aGVHD (11 of 12 concomitant ruxolitinib) achieved an ORR of 67% and CR of 25% at Day 28- -Median survival benefits in TR-aGVHD participants compare favorably to historical controlsneihulizumab was well tolerated, with similar safety profiles observed when given alone or in combination with ruxolitinib- SAN FRANCISCO, Dec. 10, 2022 (GLOBE NEWSWIRE) -- AltruBio Inc. (“AltruBio” or “the Company”), a clinical stage biotech company dedicated to the development of novel therapeutics for the treatment of immunological diseases with high unmet medical needs, today announced the presentation of new data from its completed Phase 1b clinical trial evaluating ALTB-168 in patients with steroid-refractory (SR-aGVHD) or treatment-refractory (TR-aGVHD) acute graft-versus-host-disease at the 64th American Society of Hematology (ASH) Annual Meeting, taking place December 10-13, 2022 in New Orleans, La. The data will be presented in a poster by clinical trial investigator, Sameem Abedin, M.D., Assistant Professor, Medical College of Wisconsin, Cancer Center, Froedtert Hospital Medical. “The promising efficacy, positive safety and tolerability of ALTB-168 is highly encouraging especially in this patient population that has minimal treatment options,” said Dr. Sameem Abedin, M.D., Assistant Professor, Medical College of Wisconsin, Cancer Center, Froedtert Hospital Medical, and a principal investigator participating in the clinical trial. “60% of patients with aGVHD do not respond to corticosteroids as first line treatment, and those that do not respond to any treatment have extremely poor outcomes. There is an urgent need to provide effective and long-lasting treatment options with less side effects.” Jesse Hall, M.D., Chief Medical Officer of AltruBio added, “We’re pleased to share efficacy data demonstrating that treatment with an immune checkpoint enhancer, ALTB-168, has the potential to improve outcomes in patients with aGVHD. The clinical results in this indication validated the strategy of targeting PSGL-1 to control chronically active T cell-related immunological disorders and restore immune balance. Combined with previous data to date showing that ALTB-168 has been well tolerated in close to 200 patients in four autoimmune diseases, we believe this supports ALTB-168’s first-in-class and clinically validated mechanism of action, derisking our next generation immune checkpoint enhancer ALTB-268. ALTB-268 has the same mechanism of action as ALTB-168 with a greater potency that allows for subcutaneous delivery enabling pursuit of different indications than ALTB-168. We look forward to sharing final data from this trial and preliminary Phase 1 data from ALTB-268 in 2023.”Key data highlights from the ALTB-168 multiple dose portion of the Phase 1 trial with ruxolitinib from 14 evaluable SR-aGVHD/TR-aGVHD patients to date, include: Overall response rate (ORR) of 67% in SR-aGVHD patients (N=12) and a complete response (CR) of 17% as measured by best responseORR of 67% in TR-aGVHD patients (11 of 12 concomitant ruxolitinib) at the multiple dose phase of 6-4-4-4 mg/kg – a COR of 25% at Day 28.Five SR-aGVHD patients and six TR-aGVHD patients were alive at the end of the study (Visit day 180).Corticosteroid reductions were achieved in a significant portion of TR-aGVHD participantsSafety results were comparable between the SR and TR cohorts Key data highlights from the ALTB-168 single dose portion of the Phase 1 trial from 13 evaluable SR-aGVHD patients to date, include: Best response ORR of 86% (N=7) at the 3 mg/kg dose and a best response ORR of 50% (N=6) at the 6 mg/kg dose – this includes six CRs at the 3 mg/kg dose and two CRs and 1 PR at the 6 mg/kg dose at Day 28. ASH Presentation Details: Title: Neihulizumab (ALTB-168) in Patients with Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) or Treatment-Refractory Acute Graft-Versus-Host Disease (TR-aGVHD)Abstract #: 163027Presenter: Sameem Abedin, M.D., Assistant Professor Medical College of Wisconsin, Cancer Center – Froedtert Hospital Medical For more information on the 64th American Society of Hematology (ASH) Annual Meeting and how to register, visit the website. About ALTB-168ALTB-168 is an immune checkpoint enhancer that regulates T cell homeostasis. The unique mechanism of action of this agonist antibody maintains T cell homeostasis by preferentially inducing downregulation of activated T cells, potentially sparing resting T cells and early-activated T cells. Because pathogenic T cells involved in inflammatory conditions are usually in an activated and/or auto-activated states, eliminating this population of cells can potentially control inflammation in T cell associated diseases, such as GvHD. ALTB-168 is being evaluated in a Phase 1 study (NCT03327857) to establish the pharmacokinetics, pharmacodynamics, safety and efficacy profiles in patients with steroid-refractory or treatment refractory acute graft-versus-host disease (SR/TR-aGVHD). About AltruBio Inc.AltruBio is a privately held biotechnology company headquartered in San Francisco that is focused on developing novel therapeutics for the treatment of immunological diseases with high unmet medical needs. The company has leveraged its deep understanding of the role PSGL-1 plays as an immune checkpoint regulator protein to develop a platform for T-cell mediated immunological diseases. Its first-generation molecule, ALTB-168, an immune checkpoint agonist antibody targeting PSGL-1/CD162 has achieved proof of mechanism in four autoimmune and inflammatory diseases including ulcerative colitis, steroid refractory acute graft-versus-host disease (SR-aGVHD), psoriatic arthritis, and psoriasis. The next-generation PSGL-1 agonist ALTB-268 is a tetravalent version of ALTB-168 and has demonstrated high potency via the same mechanism, which makes it suitable for subcutaneous administration in the proven indications and is advancing toward IND for multiple autoimmune and inflammatory disorders. Note on Forward-Looking StatementsStatements made in this news release that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as expects, believes, intends, and similar expressions are intended to identify forward-looking statements. Actual results may differ materially from those projected in any forward-looking statement. Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as the Company's ability to raise additional capital, and risks related to the Company's ability to initiate, and enroll patients in, planned clinical trials. You should not place undue reliance on any forward-looking statements. The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by law. Contacts AltruBio Inc: +1-415-655-6603+886-2-2627-2707info@altrubio.com Media Contact:Darren Opland, PhDLifeSci Communications+1-646-627-8387darren@lifescicomms.com

Clinical ResultPhase 1ImmunotherapyASHAACR

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