Changes in leucocyte populations following murine bifunctional antibody infusion in colon cancer patients

Abstract

SUMMARY This study was undertaken to determine whether infusion of a unique ZCE/CHA bifunctional antibody (BFA, 5–40 mg) could alter the composition and functions of peripheral blood leucocytes in 18 patients with colon cancer. The BFA is made by combining chemically the Fab’fragments of two murine monoclonal antibodies. One fragment (ZCE 025) binds to the carcino-embryonic antigen (CEA) and the other (CHA 255) to an epitope, present on an In -benzyl EDTA analog of bleomycin (BLEDTA IV) and on 111In-hydroxy-ethyl-thiourca benzyl EDTA (EOTUBE). The radiolabelled epitope (111ln-BLEDTA IV or 111In-EOTUBE) was given 4 days after pre-localization with BFA. Peripheral blood samples were tested before BFA infusion, at the end of infusion (1 h later), and at 4 and 7 days post-infusion. A 50% or greater suppression in lymphocyte responsiveness to phytohaemagglutinin (PHA) and concanavalin A (Con A) was seen in 13 out of 18 and 12 out of 18 subjects, respectively, at some time after BFA infusion; this was especially evident in those patients with prc-infusion stimulation indices of > 50 (PHA) and/or > 10 (Con A). In contrast, natural killer (NIC) cell cytotoxicity and oxygen radical production increased in five out of 15 and in seven out of 18 subjects, respectively. Little or no change was observed in CD3, CD4, CDS. CD16, and CD19 markers on lymphocyte subpopulations as determined by flow cytometry. These data suggest that significant changes in mitogen-induced lymphoproliferation. NK cell cytotoxicity. and oxygen radical production can occur in a substantial proportion of cancer patients after infusion of the ZCE/ CH A bifunctional antibody system. The immunomodulation was unrelated to initial BFA dose, dose of BFA as a carrier, or to subsequent infusion of either form of the 111In cpilope. The clinical significance of these phenomena, if any, remains to be determined.