THE THYMUS: SCHOOL FOR T-CELLS

Scientific Focus

Immune Tolerance IS at the core of most remaining unmet medical need - and the thymus controls central immune tolerance

Diagram explaining immune tolerance, self and non-self recognition, thymic function, and immune imbalance related to aging or injury.

THE THYMUS HAS A CRITICAL ROLE IN ESTABLISHING AND MAINTAINING IMMUNE TOLERANCE

  • “The school for T cells”: The thymus is the primary immune organ which provides education for the developing adaptive immune system, predominantly the T cell compartment

  • It facilitates positive selection for TCR-HLA binding, and negative selection of T cells that bind too strongly to self-antigens. This results in an adaptive immune system that recognizes pathogens but is tolerant to self [1]

  • The thymus starts to involute after two years of age, with loss accelerated after puberty. If the thymus is partially maintained into adult age, recirculation of activated T cells to the thymus is believed to maintain self-tolerance, cancer surveillance, and immune regulation [2]

T CELL DEVELOPMENT IN THE THYMUS

  • Hematopoietic progenitor cells enter the thymus and mature through positive and negative selection into CD8+ T cells and CD4+ T cells and Tregs [3]

Diagram of immune response in the thymus, bone marrow, cortex, medulla, and corticomedullary junction, showing different immune cells and processes.

1. Lin et al. Revisiting the Thymus: the origin of T cells. Frontiers in Immunology 2023
2. Kooshesh et al. Health Consequences of Thymus Removal in Adults. NEJM 2023
3. Perrino et al. Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs. Frontiers in Immunology 2024

Thymic Insufficiency Leads to Immune Disease – TOLERANCE BIO STRIVES TO PRESERVE, RESTORE, AND MODULaTE THE THYMUS

Illustration of the human thymus gland highlighted in orange, a graph titled "Thymic Involution" showing a decline in the thymus cortex volume with age, and a microscopic view of cells.
Bar chart showing increased risks associated with adult thymectomy, including 300% higher mortality, 200% higher cancer risk, and 50% higher autoimmunity risk, with a red dashed line at a relative risk of 1.
Graph showing that increased thymus activity correlates with higher survival probability in elderly populations over time, with two lines representing different TREC values.
Comparison of tissue samples showing age-related thymic involution, with a young thymus on the left and an old thymus on the right, both stained purple.

THE PROBLEM

Thymic involution/loss leads to immune disease and increased mortality

  • AGE-RELATED THYMIC INVOLUTION: The thymus is the first organ to start to atrophy during adolescence, leading to reduced T cell output. Maintaining thymus function as adults may lead to longer life in better health with less immune disease [1-4]

  • ACUTE THYMIC INVOLUTION: Caused by surgery, medications (steroids, immune-suppressants, chemotherapy), infection, inflammation

  • CONGENITAL THYMIC DEFECTS: DiGeorge syndrome, ultra-orphan congenital athymia, Down and Good's syndromes [5]    

  • Thymus impairment, failure, or removal leads to increased risk for cancer, autoimmunity, infection, and allergy [6-7]

1. Steinmann et al. The Involution of the Ageing Human Thymic Epithelium is Independent of Puberty. Scandinavian Journal of Immunology 1985
2. Duah et al. Thymus degeneration and regeneration. Frontiers in Immunology 2021
3. Srinivasan et al. Age-Related Changes in Thymic Central Tolerance. Frontiers in Immunology 2021
4. Paparazzo et al. Thymic function and survival at advanced ages in nursing home residents from Southern Italy. Immunity and Ageing 2023
5. Marx et al. Thymus and Autoimmunity. Seminars in Immunopathology 2021
6. Kooshesh et al. Health Consequences of Thymus Removal in Adults. NEJM 2023
7. Biggs et al. Chromosome 22q11.2 Deletion (DiGeorge Syndrome): Immunologic Features, Diagnosis, and Management. Current Allergy Asthma Reports 2023

THE SOLUTION

  • DELAY/PREVENT NATURAL AND ACCELERATED THYMIC INVOLUTION WITH DRUGS/THERAPEUTICS 

    1. For acute and age-related thymic involution 

  • RESTORE THYMIC FUNCTION WITH ADULT STEM CELL-DERIVED THYMIC EPITHELIAL CELL IMPLANTS

    1. Bio-engineered thymus made from iPSC-derived thymic epithelial cells 

    2. Disease-specific thymic cells

Delay/prevent thymic involution, and restore thymic function if lost

OUR PIPELINE

Table comparing different immunotherapy modalities, including monoclonal antibodies, fusion proteins, and cell therapies, with details on products, development focus, and clinical stages.
Table comparing different immunotherapy modalities, including monoclonal antibodies, fusion proteins, and cell therapies, with details on products, development focus, and clinical stages.