Abstract 1324: Superior anti-tumor activity of GL205, an allogeneic anti-CD5 CAR-NK for treating T-cell malignancies

Abstract T cell malignancies are rare and intractable diseases with fewer treatment options and higher unmet needs compared to B-cell lymphomas. Chemotherapy such as CHOP has been used as the standard therapy for treatment of T cell malignancies, but clinical outcome is not a promising and alternative treatments are needed. Currently, Brentuximab Vedotin, an antibody-drug conjugate that targets CD30 is widely used for Hodgkin lymphoma, ALCL and CTCL. However, the application is limited to specific subtypes because CD30 expression is restricted to some subsets of T-cell lymphoma. CD5 is an attractive target for cancer immunotherapy because it is commonly expressed in most of T cell malignancies. Although CD5 CAR-T cell products have demonstrated the anti-cancer efficacy, there are several disadvantages including 1) challenges due to difficulties in manufacturing process caused by fratricide, 2) product contamination by CAR-introduced patient’s malignant T cells, 3) severe side effects such as CRS and neurotoxicity. Therefore, CD5 CAR-NK as allogeneic anti-tumor therapy can be an alternative for treatment of T cell malignancies. GL205, cord blood-derived CD5 CAR-NK, is genetically modified to express CD5-directed CAR and simultaneously produce IL-15 which supports the NK survival and proliferation. GL205 is ex-vivo expanded, cryopreserved cell therapy product comprising of pure NK cells (99%) with high CD5 CAR expression (90%). GL205 showed significantly higher in vitro direct-killing efficacy against CD5+ tumor cells compared to donor matched CBNK. IFN-γ and IL-15 release from GL205 was significantly increased after co-incubation with CD5+ tumor cells. In xenograft mouse model, GL205 administration exhibited a greater survival rate and low tumor burden compared to vehicle group. In addition, GL205 was detected in blood for 3 months, demonstrating in vivo long-term persistence. In conclusion, GL205 could be a valuable and off-the-shelf allogeneic therapeutic option for treating T cell malignancies. Citation Format: Miyoung Jung, Seung Min Kim, Eunsol Lee, Hyunseung Sun, Jaeyoung Yoo, Hwi Wan Choi, Subin An, Sunglim Cho, Bokyung Min. Superior anti-tumor activity of GL205, an allogeneic anti-CD5 CAR-NK for treating T-cell malignancies abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1324.