Chimerization of LL2, a rapidly internalizing antibody specific for B cell lymphoma

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Murine monoclonal antibody LL2 (mLL2) shows efficacy in diagnosing and treating non-Hodgkin's B cell lymphoma.
• Radiolabeled mLL2 and its fragments coupled to Pseudomonas exotoxin target human B cell lymphoma in mice.

Purpose of the Study:

• To create a chimeric LL2 (cLL2) antibody by combining murine variable domains with human constant domains.
• To evaluate the immunoreactivity, binding, and internalization of cLL2 compared to mLL2.

Main Methods:

• Obtained DNA sequences for VK and VH domains of mLL2.
• Combined mLL2 domains with human kappa and IgG1 constant regions.
• Expressed chimeric antibody in SP2/0 cells.
• Performed competitive binding assays and internalization studies using Raji cells.

Main Results:

• Chimerization did not affect the immunoreactivity of LL2 antibody.
• Both mLL2 and cLL2 demonstrated equivalent binding and rapid internalization by Raji cells.
• Internalization rates for mLL2 and cLL2 were nearly identical (Ke values of 0.106 and 0.118 min-1).

Conclusions:

• Chimeric LL2 (cLL2) antibody preserves the biological activity of the murine counterpart (mLL2).
• cLL2 shows potential as a less immunogenic therapeutic agent for B cell lymphomas.
• Further studies are ongoing to evaluate cLL2 as a therapeutic immunoconjugate.