Tessera Therapeutics Presents In Vivo Advances for Sickle Cell and T-Cell Therapies at ASH 66th Meeting

Tessera Therapeutics is pushing forward the boundaries of genome engineering with its innovative Gene Writing and delivery platforms. Recent preclinical advances were unveiled at the 66th American Society of Hematology (ASH) Annual Meeting, highlighting potential therapies for sickle cell disease (SCD) and T cell-related treatments. The development of these novel approaches has shown promise in rewriting the hemoglobin subunit beta (HBB) gene, associated with SCD, and generating chimeric antigen receptor (CAR) T cells for cancer therapy.

In the pursuit of treating sickle cell disease, Tessera Therapeutics has achieved significant strides in gene editing within hematopoietic stem cells (HSCs). Utilizing their proprietary lipid nanoparticles (LNPs), they have successfully rewritten the HBB gene in vivo, reaching promising results in both humanized mice and non-human primates (NHPs). A single intravenous administration of this gene editing formulation resulted in an average of 62% HBB gene rewriting in LT-HSCs of humanized mice and 24% in NHPs. These results suggest that gene editing efficiencies can reach therapeutic levels that are anticipated to reverse the sickle cell phenotype, as demonstrated by human mixed-donor chimerism studies.

Further investigations have shown the potential to achieve high-efficiency in vivo rewriting in LT-HSCs using a surrogate reagent targeting beta-2 microglobulin (B2M). The study demonstrated a remarkable 76% rewriting efficiency in NHPs, with stable editing observed up to day 84. This efficiency across multiple blood cell lineages supports the potential functional contribution of edited HSCs to the overall hematopoietic process. The success of these in vivo results is largely attributed to Tessera’s non-viral delivery platform, which has notably enhanced bone marrow delivery and reduced liver targeting.

In parallel, Tessera is making strides towards advancing in vivo T-cell therapies. Their Gene Writers formulated in LNPs have shown the capability to integrate CAR transgenes, specifically targeting CD20 in resting NHP T cells, achieving an impressive average of 60% CAR writing in vitro. This approach has facilitated the creation of functional CAR-T cells that effectively target and eliminate tumor cells. In tumor-bearing xenograft mouse models, a single intravenous infusion of the Gene Writer formulation led to the generation of CD19-targeted CAR-T cells in vivo, successfully expanding and eradicating tumor burdens.

Additionally, Tessera’s delivery of Gene Writer and CAR template RNAs targeting B-cell maturation antigen (BCMA) to T cells has underscored its potential in oncology. These functional CAR-T cells have proven effective both in vitro and in vivo, as evidenced by their tumor cell-killing capabilities. Furthermore, in a naïve humanized mouse model with resting T cells, an average of 30% CAR writing was accomplished, leading to the depletion of human B cells. This finding highlights the therapeutic potential of this approach for treating autoimmune diseases.

Overall, Tessera Therapeutics is at the forefront of developing transformative genetic medicines through their pioneering Gene Writing and delivery platforms. Their work is opening new therapeutic avenues, not only for diseases caused by single-gene errors but also for modifying inherited risk factors for common diseases and engineering cells for cancer and potentially autoimmune disease treatments. Founded by Flagship Pioneering, Tessera continues to advance its mission to transform human health and sustainability through innovative biotechnological solutions.