New cell therapy offers path to stop immune rejection of blood treatments
Researchers developed immune cells that could prevent hemophilia patients from rejecting their life-saving factor VIII therapy—a breakthrough that could extend treatment viability and reduce costs. The same immune-modulation approach is being tested against brain tumors, suggesting broader applications in cancer and rare disease markets.
Originaltitel: Immune tolerance: induction and disruption for therapeutic immune modulation
<p>This study investigated the tolerance induction and disruption of immune tolerance as strategies for immune modulation.</p><p>For induction of immune tolerance, novel monocyte-derived tolerogenic dendritic cells (ItolDCs) were generated, and their ability to modulate the immune system was assessed using <em>in vitro </em>assays in hemophilia A patients who had developed neutralizing antibodies against their factor VIII replacement therapy. The cells were characterized, their functionality was assessed, and their feasibility as a safe cell therapy was further evaluated using both <em>in vitro </em>and <em>in vivo </em>studies for the induction of immune tolerance against factor VIII.</p><p>For research on disruption of immune tolerance, meningioma, the most common brain tumor, was studied. To map the immune cell composition in meningiomas, a protocol was optimized for shorter enzymatic digestion, which breaks down the tissue into single-cell suspensions of viable immune cells. Since CD8+ T cells are vital in tumor suppression, further studies were conducted to explore their characteristics and identify possible targetable processes for immunotherapy.</p><p>To investigate both induction and disruption of immune tolerance, various techniques were employed, including flow cytometry, immunohistochemistry, and functional-cell-based assays.</p><p>Our investigation demonstrated that ItolDCs are a feasible and safe option for cell therapy aimed at inducing immune tolerance. Thus, factor VIII-loaded ItolDCs are ready for clinical evaluation to reduce inhibitor levels in patients with hemophilia A.</p><p>Several tolerance-associated markers (PD-1, TIM-3, TIGIT, and LAG-3) were identified in CD8+ T cells in meningioma. These findings highlight how tumor cells may evade immune defenses and suggest potential immunotherapeutic targets, including immune checkpoint inhibitors.</p><p>Taken together, various approaches may be employed for immune modulations to either induce or disrupt immune tolerance.</p>