Biologic properties of a Ch2 domain‐deleted recombinant immunoglobulin

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Abstract
Monoclonal antibody (MAb) B72.3 reacts with TAG‐72, a high‐molecular‐weight mucin expressed on several types of human carcinoma, and is currently being used in clinical trials for the diagnosis and therapy of human carcinoma. An expression construct containing cDNA encoding an immunoglobulin (Ig) heavy chain, with the variable region of murine MAb B72.3 and a human Ig constant region with a deletion of the CH2 domain, was generated. Immunoglobulin from the transfectoma with the highest expression of the TAG‐72 immunoreactive antibody was designated MAb chimeric (c) B72.3°CH2. The pharmacokinetics of serum clearance of iodine‐labeled MAbs cB72.3°CH2 and the intact cB72.3 were compared in athymic mice. By 24 hr, less than 1% of the cB72.3°CH2 was left in the plasma, while 36% of the cB72.3 still remained. The T1/2β values of the cB72.3°CH2 and cB72.3 MAbs were 1.7 and 2.4 hr, respectively. The T1/2β values were 7.8 hr for the domain‐deleted cMAb and 48.9 hr for cB72.3. Biodistribution studies in athymic mice bearing LS‐174T xenografts showed a reduction in the percentage of injected dose per gram in tumor with 1311‐cB72.3°CH2; however, the 1311‐cB72.3ΔCH2 both localized to tumors faster and cleared from the blood faster than the 1251‐cB72.3 MAb. Only trace amounts of the 1311‐CB72.3°CH2 were detected in normal tissues, including kidney. The faster clearance rate, more rapid tumor targeting and lack of metabolic uptake in normal tissues demonstrated with the iodine‐labeled CH2 domain‐deleted cMAb may be an advantage for certain clinical protocols.