Immunome Research
Open Access
ISSN: 1745-7580
+44-20-4587-4809
ISSN: 1745-7580
+44-20-4587-4809
De-Kuan Chang
Dana-Farber Cancer Institute, USA
Posters & Accepted Abstracts: Immunome Res
In 10-20% of the cases of chronic lymphocytic leukemia of B-cell phenotype (B-CLL), the IGHV169 germline is utilized as VH gene of the B-cell receptor (BCR). Mouse G6 (MuG6) is an anti-idiotypic monoclonal antibody discovered in a screen against rheumatoid factors (RFs) that binds with high affinity to an idiotope expressed on the 51p1 alleles of IGHV169 germline gene encoded antibodies (G6-id+). The finding that unmutated IGHV169 encoded BCRs are frequently expressed on BCLL cells provides an opportunity for antiidiotype monoclonal antibody immunotherapy. In this study, we first showed that MuG6 can deplete B-cells encoding IGHV1-69 BCRs using a novel humanized GTL mouse model. Next, we humanized MuG6 and demonstrated that the humanized antibodies (HuG6s), especially HuG6.3, displayed ~2fold higher binding affinity for G6id+ antibody compared to the parental MuG6. Additional studies showed that HuG6.3 was able to kill G6id+ BCR expressing cells and patient BCLL cells through antibody-dependent cellmediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Finally, both MuG6 and HuG6.3 mediate in vivo depletion of B-CLL cells in NSG mice. These data suggest that HuG6.3 may provide a new precision medicine to selectively kill IGHV169 encoding G6id+ BCLL cells.