Iltamiocel (Cook MyoSite)

Antibody-mimetic drug conjugate (AMDC) is a cancer cell-targeted drug delivery system based on the non-covalent binding of mutated streptavidin and modified biotin, namely Cupid and Psyche. However, the development of AMDCs is hampered by difficulties in post-translational modification or poor internalization activity. Here, we report an expression, refolding, and purification method for AMDC using a variable heavy chain of heavy chain-only antibodies (VHHs). Monomeric anti-HER2 VHH fused to Cupid was expressed in Escherichia coli inclusion bodies. Solubilization and refolding at optimized reducing conditions and pH levels were selected to form a functional, tetrameric protein (anti-HER2 VHH-Cupid) that can be easily purified based on molecular weight. Anti-HER2 VHH-Cupid non-covalently creates a tight complex with Psyche linked to a potent DNA-alkylating agent, duocarmycin. This complex can be absorbed by the HER2-expressing human breast cancer cell line, KPL-4, and kills KPL-4 cells in vitro and in vivo. The production of a targeting protein with internalizing activity, combined with the non-covalent conjugation of a highly potent payload, renders AMDC a promising platform for developing cancer-targeted therapy.

To examine the safety and efficacy of iltamiocel, an investigational cellular therapy of autologous muscle-derived cells, as a treatment for fecal incontinence (FI) in adults.

Limited therapeutic options are available for patients with FI refractory to conservative treatments. Cell therapy using autologous muscle-derived cells represents a promising, minimally invasive approach for restoring anal sphincter function.

In this multicenter, prospective, non-randomized study, 48 participants were treated with a single iltamiocel dose of 250×106 cells. The primary outcome was the incidence of product or procedure-related adverse events (AEs) and serious AEs. Secondary outcomes were changes in the number of FI episodes, Cleveland Clinic Incontinence Score, Fecal Incontinence Quality of Life, and anorectal manometry at 3, 6, and 12 months compared to baseline.

No serious AEs and only one product-related AE of inflammation at the injection site were reported. At 12 months, there was a reduction in median FI episodes (−6.0; 95% confidence interval (CI): −10.0, −1.0) and days with episodes (−4.0; 95% CI: −8.0, −1.0). A ≥50% reduction in FI episodes was observed in 53.7% of participants, and 24.4% had complete restoration of continence. Symptom severity and quality of life improved with mean Cleveland Clinic Incontinence Score reduction (-2.9; 95% CI: −3.7, −2.1), and Fecal Incontinence Quality of Life increased (2.2; 95% CI:1.4, 2.9). No significant changes were detected in anorectal manometry measurements. A history of episiotomy was significantly associated with treatment response in multivariate analysis.

The administration of iltamiocel cellular therapy is safe. Iltamiocel shows promise for significantly improving fecal incontinence symptoms and quality of life.