Work

17P KBA1413: An antibody derived from a cured AML patient, recognizes a unique glycoepitope shared by AML, MDS and several solid cancer cells

Year: 2025

Type: article

Abstract: Background: The use of human B cells for antigen-and antibody discovery is on the rise due to the emergence of new techniques to tap into the human antigen-experienced B cell repertoire.To identify new targets for immunotherapy, we screened the B-cell repertoire of a patient with high-risk acute myeloid leukemia (AML) who mounted a potent graft versus leukemia immune response following allogeneic stem cell transplantation.Methods: KBA1413 is a fully human antibody identified using Kling's proprietary B cell screening platform, Kling-Select.KBA1413 derives from the B cells of an AML patient who remains in long term remission following allogeneic hematopoietic stem cell transplantation.Results: The antibody recognizes a unique, previously undescribed, sialylated epitope present on CD43 (CD43s).This epitope is expressed on across all AML subtypes and on myelodysplastic syndrome (MDS), as illustrated by KBA1413 reactivity to with freshly isolated blasts of over 60 randomly selected AML and MDS patients.In addition, KBA1413 also recognizes several solid tumor indications, including melanoma and breast cancer.KBA1413 triggers NK-mediated antibody dependent cell-mediated cytotoxicity (ADCC) against AML cells both in vitro and in vivo in human immune system mice xenografted with AML cells, suggesting that KBA1413 played a role in the graft versus leukemia response of the original donor patient.Conclusions: To increase its therapeutic potential KBA1413 was made into a bispecific T-cell engaging antibody (bTCE) that induced potent cytotoxicity in vitro and in vivo on cell lines and primary AML.Bifunctional targeting of AML with KBA1413 and a CD33 binder induced potent ADCC activitycytotoxicity in vitro, outperforming single agent activity.To increase the affinity of KBA1413, we further optimized binding of KBA1413 with employed the Kling-Evolve platform, this allows for the in vitro maturation of B cell clones against targets of interest.We are further exploring the therapeutic potential of KBA1413 with affinity matured variants produced with Kling-Evolve.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2025.104173