INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing <i>Escherichia coli</i>-associated HUS (STEC-HUS) is one of the leading causes of AKI in childr...
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MDPI AG
2025-06-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/17/6/282 |
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| author | Marta Rivas Mariana Pichel Vanesa Zylberman Mariana Colonna Marina Valerio Carolina Massa Romina Pardo Andrés E. Ciocchini Santiago Sanguineti Ian Roubicek Linus Spatz Fernando Alberto Goldbaum |
| author_facet | Marta Rivas Mariana Pichel Vanesa Zylberman Mariana Colonna Marina Valerio Carolina Massa Romina Pardo Andrés E. Ciocchini Santiago Sanguineti Ian Roubicek Linus Spatz Fernando Alberto Goldbaum |
| author_sort | Marta Rivas |
| collection | DOAJ |
| description | Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing <i>Escherichia coli</i>-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children die during the acute phase, and about 30% experience long-term renal sequelae. Argentina has the highest incidence of STEC-HUS globally. Given the prominent role of Stx in its pathophysiology, STEC-HUS is considered more of a toxemia than a bacterial disease. Stx transport occurs before and after the STEC-HUS onset, allowing for the distinction between an early toxemia phase and an advanced toxemia phase. In this review, we present our efforts to develop INM004, an anti-Stx treatment aimed at ameliorating or preventing the clinical consequences of STEC-HUS. We describe the protein engineering that facilitated this development and the clinical path to demonstrate the safety and efficacy of INM004. This immunotherapy could represent a new step in the treatment of STEC-HUS, which could potentially prevent long-term damage. If phase 3 trials are successful, earlier and broader use of INM004 is envisioned. We also discuss the potential impact of INM004 therapy, targeted vaccination strategies, and new diagnostic tools for this disease. |
| format | Article |
| id | doaj-art-c661d326ada6409f9b69be6cebcea3f7 |
| institution | Kabale University |
| issn | 2072-6651 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj-art-c661d326ada6409f9b69be6cebcea3f72025-08-20T03:32:32ZengMDPI AGToxins2072-66512025-06-0117628210.3390/toxins17060282INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic SyndromeMarta Rivas0Mariana Pichel1Vanesa Zylberman2Mariana Colonna3Marina Valerio4Carolina Massa5Romina Pardo6Andrés E. Ciocchini7Santiago Sanguineti8Ian Roubicek9Linus Spatz10Fernando Alberto Goldbaum11Inmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaConsejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Godoy Cruz 2290, Ciudad Autonoma de Buenos Aires 1425, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaInmunova S.A., Av. 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaHemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing <i>Escherichia coli</i>-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children die during the acute phase, and about 30% experience long-term renal sequelae. Argentina has the highest incidence of STEC-HUS globally. Given the prominent role of Stx in its pathophysiology, STEC-HUS is considered more of a toxemia than a bacterial disease. Stx transport occurs before and after the STEC-HUS onset, allowing for the distinction between an early toxemia phase and an advanced toxemia phase. In this review, we present our efforts to develop INM004, an anti-Stx treatment aimed at ameliorating or preventing the clinical consequences of STEC-HUS. We describe the protein engineering that facilitated this development and the clinical path to demonstrate the safety and efficacy of INM004. This immunotherapy could represent a new step in the treatment of STEC-HUS, which could potentially prevent long-term damage. If phase 3 trials are successful, earlier and broader use of INM004 is envisioned. We also discuss the potential impact of INM004 therapy, targeted vaccination strategies, and new diagnostic tools for this disease.https://www.mdpi.com/2072-6651/17/6/282Shiga toxinhemolytic uremic syndromeSTEC-HUSdiagnosisimmunotherapy treatmentvaccine development |
| spellingShingle | Marta Rivas Mariana Pichel Vanesa Zylberman Mariana Colonna Marina Valerio Carolina Massa Romina Pardo Andrés E. Ciocchini Santiago Sanguineti Ian Roubicek Linus Spatz Fernando Alberto Goldbaum INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome Toxins Shiga toxin hemolytic uremic syndrome STEC-HUS diagnosis immunotherapy treatment vaccine development |
| title | INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome |
| title_full | INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome |
| title_fullStr | INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome |
| title_full_unstemmed | INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome |
| title_short | INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome |
| title_sort | inm004 polyclonal neutralizing antibodies against shiga toxin as a treatment for hemolytic uremic syndrome |
| topic | Shiga toxin hemolytic uremic syndrome STEC-HUS diagnosis immunotherapy treatment vaccine development |
| url | https://www.mdpi.com/2072-6651/17/6/282 |
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