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Engineered MSCs could treat GVHD

Image by Megan Farrell
Mesenchymal stem cells in a hyaluronic acid hydrogel

LAUSANNE, SWITZERLAND—A mesenchymal stem cell (MSC) product could treat acute graft-versus-host disease (GVHD), according to preclinical research.

The product, apceth-201, improved symptoms of GVHD and prolonged survival in two mouse models.

Researchers described results with apceth-201 in a poster presentation at the Annual Congress of the European Society of Gene and Cell Therapy.

Most of the researchers involved in this study work for apceth Biopharma, the company developing apceth-201.

Apceth-201 consists of allogeneic human MSCs that have been genetically modified to express alpha-1 antitrypsin, a protease inhibitor exerting anti-inflammatory and tissue-protective functions.

In vitro assays showed that apceth-201 suppresses T-cell proliferation, polarizes macrophages to an anti-inflammatory M2 type, converts dendritic cells to a tolerogenic phenotype, and increases induction of regulatory T cells.

Apeceth-201 also demonstrated activity in vivo.

In a humanized GVHD model, treatment with apceth-201 improved bone marrow cellularity and reduced levels of inflammatory markers.

Additionally, mice treated with apceth-201 had double the median survival of mice treated with native MSCs.

Researchers also tested the effects of apceth-201 against GVHD in a model of haploidentical hematopoietic stem cell transplant.

All control mice succumbed to GVHD within 22 days, but more than half of mice treated with apceth-201 survived until the end of the experiment, which was 100 days.

All of the survivors had complete resolution of GVHD symptoms.

The researchers also said apceth-201 was safe. It did not impair T-cell-dependent antibody responses, and host resistance was similar in treated mice and controls.

“We are very excited with these results that clearly show the transformative therapeutic potential of apceth-201 in an immune-mediated disease with high unmet medical need and few treatment options,” said Christine Guenther, CEO of apceth Biopharma.

“Based on these promising and impressive data, we are currently preparing to initiate a phase 1/2 clinical study assessing the safety and efficacy of apceth-201 in adult steroid-refractory GVHD patients.”

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Image by Megan Farrell
Mesenchymal stem cells in a hyaluronic acid hydrogel

LAUSANNE, SWITZERLAND—A mesenchymal stem cell (MSC) product could treat acute graft-versus-host disease (GVHD), according to preclinical research.

The product, apceth-201, improved symptoms of GVHD and prolonged survival in two mouse models.

Researchers described results with apceth-201 in a poster presentation at the Annual Congress of the European Society of Gene and Cell Therapy.

Most of the researchers involved in this study work for apceth Biopharma, the company developing apceth-201.

Apceth-201 consists of allogeneic human MSCs that have been genetically modified to express alpha-1 antitrypsin, a protease inhibitor exerting anti-inflammatory and tissue-protective functions.

In vitro assays showed that apceth-201 suppresses T-cell proliferation, polarizes macrophages to an anti-inflammatory M2 type, converts dendritic cells to a tolerogenic phenotype, and increases induction of regulatory T cells.

Apeceth-201 also demonstrated activity in vivo.

In a humanized GVHD model, treatment with apceth-201 improved bone marrow cellularity and reduced levels of inflammatory markers.

Additionally, mice treated with apceth-201 had double the median survival of mice treated with native MSCs.

Researchers also tested the effects of apceth-201 against GVHD in a model of haploidentical hematopoietic stem cell transplant.

All control mice succumbed to GVHD within 22 days, but more than half of mice treated with apceth-201 survived until the end of the experiment, which was 100 days.

All of the survivors had complete resolution of GVHD symptoms.

The researchers also said apceth-201 was safe. It did not impair T-cell-dependent antibody responses, and host resistance was similar in treated mice and controls.

“We are very excited with these results that clearly show the transformative therapeutic potential of apceth-201 in an immune-mediated disease with high unmet medical need and few treatment options,” said Christine Guenther, CEO of apceth Biopharma.

“Based on these promising and impressive data, we are currently preparing to initiate a phase 1/2 clinical study assessing the safety and efficacy of apceth-201 in adult steroid-refractory GVHD patients.”

Image by Megan Farrell
Mesenchymal stem cells in a hyaluronic acid hydrogel

LAUSANNE, SWITZERLAND—A mesenchymal stem cell (MSC) product could treat acute graft-versus-host disease (GVHD), according to preclinical research.

The product, apceth-201, improved symptoms of GVHD and prolonged survival in two mouse models.

Researchers described results with apceth-201 in a poster presentation at the Annual Congress of the European Society of Gene and Cell Therapy.

Most of the researchers involved in this study work for apceth Biopharma, the company developing apceth-201.

Apceth-201 consists of allogeneic human MSCs that have been genetically modified to express alpha-1 antitrypsin, a protease inhibitor exerting anti-inflammatory and tissue-protective functions.

In vitro assays showed that apceth-201 suppresses T-cell proliferation, polarizes macrophages to an anti-inflammatory M2 type, converts dendritic cells to a tolerogenic phenotype, and increases induction of regulatory T cells.

Apeceth-201 also demonstrated activity in vivo.

In a humanized GVHD model, treatment with apceth-201 improved bone marrow cellularity and reduced levels of inflammatory markers.

Additionally, mice treated with apceth-201 had double the median survival of mice treated with native MSCs.

Researchers also tested the effects of apceth-201 against GVHD in a model of haploidentical hematopoietic stem cell transplant.

All control mice succumbed to GVHD within 22 days, but more than half of mice treated with apceth-201 survived until the end of the experiment, which was 100 days.

All of the survivors had complete resolution of GVHD symptoms.

The researchers also said apceth-201 was safe. It did not impair T-cell-dependent antibody responses, and host resistance was similar in treated mice and controls.

“We are very excited with these results that clearly show the transformative therapeutic potential of apceth-201 in an immune-mediated disease with high unmet medical need and few treatment options,” said Christine Guenther, CEO of apceth Biopharma.

“Based on these promising and impressive data, we are currently preparing to initiate a phase 1/2 clinical study assessing the safety and efficacy of apceth-201 in adult steroid-refractory GVHD patients.”

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