This technology identifies both a biomarker for autoimmune hemolytic anemia (AIHA) and a potential treatment that can prevent AIHA onset (i.e., prophylactic) and mitigate disease symptoms (i.e., therapeutic) in AIHA preclinical mouse models.
Autoimmune hemolytic anemia (AIHA) is a heterogenous blood disease that is difficult to diagnose and can cause severe hemolysis and high fatality rates. AIHA can be primary (i.e., no underlying cause identified) or secondary (e.g., to infections, lymphoproliferative disorders, immunodeficiencies etc.). Of note, the incidence of AIHA secondary to immune checkpoint inhibitor immunotherapy, a therapy for many cancer patients, has risen to become the most frequent hematological adverse effect caused by immunotherapy. Treatment for AIHA includes corticosteroids and immunosuppressants; however, treatment strategies have variable success, with relapse rates up to 50% and mortality in ~11% of cases. Currently, there are no FDA-approved treatments specific for AIHA and few approaches produce treatment-free, durable remission.
This technology identifies a T cell biomarker, detectable in peripheral blood, that predicts AIHA onset and correlates with disease severity. The identified T cell biomarker secretes pro-inflammatory cytokines and stimulates B cells to produce pathogenic RBC autoantibodies. This technology also identifies a signaling pathway involved in disease onset. Leveraging the properties of the T cell biomarker and the signaling pathway that contributes to AIHA onset, this technology also identifies apyrase as an effective AIHA treatment. Using a mouse model of AIHA secondary to immune checkpoint inhibitor immunotherapy, apyrase treatment is effective as a prophylactic and therapeutic: apyrase treatment at time of the T cell biomarker appearance prevented AIHA onset and apyrase treatment after AIHA development led to symptom mitigation. Prophylactic and therapeutic treatment with apyrase decreased T cell biomarker numbers, which correlated with disease prevention and/or mitigation. This biomarker may be useful in predicting which patients on immune checkpoint inhibitor immunotherapy will develop AIHA and evaluating therapeutic efficacy. Additionally, apyrase may be used as a therapeutic in AIHA patients or those at high risk at developing AIHA.
This technology has been validated in preclinical mouse models of AIHA to mitigate disease onset and progression.
Patent Pending
IR CU24097
Licensing Contact: Sara Gusik