Allogeneic processed thymus tissue

Identification

Summary

Allogeneic processed thymus tissue is a cell transplant therapy indicated for immune reconstitution in pediatric patients with congenital athymia.

Brand Names

Rethymic

Generic Name

Allogeneic processed thymus tissue

DrugBank Accession Number

DB16736

Background

Allogeneic processed thymus tissue is used for immune reconstitution in immune disorders where the patients are severely immunocompromised due to the absence of a functional thymus, such as congenital athymia. As part of the immune system, the thymus is an organ responsible for the maturation and selection of T cells ³; thus, patients without a functional thymus experience profound immunodeficiency and are placed at higher risk for developing life-threatening or fatal infections and immune dysregulation.⁵ Congenital athymia is a rare condition that leads to the absence of a thymus at birth and a high premature mortality rate, with patients typically dying by age two or three.⁵ Multiple factors contribute to the development of congenital athymia, such as genetic abnormalities, congenital syndromes, and environmental factors. Allogeneic processed thymus tissue implantation works by migrating the recipient’s bone marrow-derived stem cells to the implanted cultured thymus tissue that develops immunocompetent naïve T cells.³

On October 8, 2021, FDA approved allogeneic processed thymus tissue-agdc, under the market name RETHYMIC, as a one-time regenerative tissue-based therapy for immune reconstitution in pediatric patients with congenital athymia: this marks the first and only FDA-approved treatment for such therapeutic indication.⁵

Type

Biotech

Groups

Approved

Biologic Classification

Cell transplant therapies
Other cell transplant therapies

Synonyms

Allogeneic processed thymus tissue-agdc
Allogeneic thymocyte depleted processed thymus tissue slices
Allogeneic thymocyte-depleted thymus tissue-agdc
Allogenic thymocyte-depleted thymus tissue-agdc

External IDs

RVT-082

Pharmacology

Indication

Allogeneic processed thymus tissue is indicated for immune reconstitution in pediatric patients with congenital athymia. It is not indicated for the treatment of patients with severe combined immunodeficiency (SCID).⁴

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Associated Conditions

Congenital athymia

Associated Therapies

Immune reconstitution

Contraindications & Blackbox Warnings

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Pharmacodynamics

Allogeneic processed thymus tissue is an engineered human thymus tissue that is used to regenerate the thymic function ⁵ and reconstitutes immunity in patients who are athymic to develop immunocompetent naïve T cells. The presence of naïve T cells in the peripheral blood of the recipient is evident of thymic function, although this effect is unlikely to be observed prior to 6-12 months following treatment with allogeneic processed thymus tissue.⁴ In recent studies of thymus transplantation, thymopoiesis in the transplanted thymus was observed within two months of transplantation and naïve T cells in the peripheral blood were detected in about three to five months after transplantation.¹ In an immune evaluation study of thymus recipients surviving beyond 1 year, recipients possessed naïve T cells with normal mitogen proliferative responses and diverse T cell receptor repertoires.²

Mechanism of action

The thymus is a critical organ of the immune system as it is responsible for the maturation and selection of thymocytes so that they ultimately become naïve T cells. Normally, T cell precursors from the bone marrow migrate to the thymus for maturation and differentiation. Congenital athymia is characterized by the absence of a thymus at birth, leading to the lack of functional T cells and profound immune deficiency; therefore, patients with congenital athymia are at high risk for developing life-threatening or fatal infections as well as autologous graft-versus-host disease.³

Allogeneic processed thymus tissue aims to restore thymic function in patients with congenital athymia. Thymus tissue is obtained from unrelated infant donors to be processed and cultured, so that the thymus tissue preserves thymic epithelial cells but lacks most of the donor thymocytes. The resulting allogeneic processed thymus tissue is then surgically implanted into the muscles of recipients with congenital athymia. T cell progenitors from the bone marrow of the recipient are migrated to the implanted allogeneic processed thymus tissue,⁴ which provides an environment for progenitor cells to undergo positive and negative selection to develop into naïve immunocompetent recipient T cells.^2,4

Absorption