T-cell malignancies exhibit resistance to the standard therapy, CHOP, which results in limited anti-tumor activity and poor prognosis. This highlights a significant unmet medical need for novel treatment strategies. Given that CD5 is ubiquitously expressed on most T-cell malignancies, it represents a highly attractive therapeutic target.
Here, we present comprehensive preclinical data on GCC2005, an allogeneic CD5 CAR-NK cell therapy. GCC2005 demonstrated significantly enhanced cytotoxicity against CD5+ tumor cells, along with a notable increase in IFN-γ and IL-15 secretion. Importantly, GCC2005 revealed minimal on-target, off-tumor toxicity, exhibiting 1.7~2 fold lower cytotoxicity against CD5+ normal cells compared to CD5+ tumor cells. Additionally, GCC2005 led to reductions in tumor burden and improved survival in a dose-dependent manner in xenograft mouse models.
In GLP-compliant studies, no GCC2005-related toxicities or neoplastic changes were observed in either the low-dose (2×106 cells/head) or high-dose (5×106 cells/head) group. Neither deaths nor general symptoms were observed in the RPMI-8402 xenograft model. Overall, GCC2005 was well tolerated with the NOAEL determined as 5×106 cells/head.
The pharmacokinetics of GCC2005 showed a consistent profile in both non-tumor-bearing and tumor-bearing models with peak levels observed approximately four weeks after the last injection. A subsequent decrease in all tissue levels was noted by day 89, eventually falling BLOQ by day 169.
These results strongly support the potential of GCC2005 as a promising therapeutic option for T-cell malignancies. Currently, GCC2005 is currently under evaluation in a Phase I clinical trial (NCT06699771) in South Korea to assess safety, tolerability, and efficacy in patients with relapsed/refractory NK and T-cell malignancies.
