Abstract 12P
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.
Methods
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.
Results
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. The antibody recognizes a unique, previously undescribed, sialylated epitope on CD43 (CD43s). CD43s is a transmembrane protein overexpressed on all AML subtypes and myelodysplastic syndrome (MDS), as illustrated by KBA1413 reactivity to freshly isolated blasts of over 60 randomly selected AML and MDS patients. In addition, KBA1413 also recognizes CD43s on 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 andin 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. 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.
Conclusions
Kling Biotherapeutics has discovered several unique cancer targets and their corresponding human antibodies that are currently in preclinical development such as targeting snRNP200 and a novel, truncated form of E-cadherin. KBA1412, a CD9-targeting human antibody is currently being evaluated in a phase 1b dose escalation and dose expansion study in patients with advanced solid tumors (ClinicalTrials.gov: NCT05501821).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
V. Clerico Mosina, M. Kedde, B. Pieters, B. Monica, K. Maijoor, R. Schotte, A. Bakker: Financial Interests, Personal, Project Lead: Kling Biotherapeutics. M. Koslowski: Financial Interests, Personal, Officer: Kling Biotherapeutics. S. Gullà: Financial Interests, Personal, Officer: Kling Biotherapeutics.