Level of anti-mouse-antibody response induced by bi-specific monoclonal antibody OC/TR in ovarian-carcinoma patients is associated with longer survival

More than 60% of cancer patients injected with intact murine monoclonal ant ibody (MAb) develop a humoral response against the antigen even after a sin gle dose. Analysis of a series of 35 ovarian-cancer patients entered in pha se-I and -II clinical studies of T-cells retargeted with the bi-specific F( ab')(2) OC/TR revealed: (i) a detectable human anti-mouse antibody (HAMA) r esponse in 31/35 (88%) patients, with high MAMA levels (greater than or equ al to 150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between MAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high MAMA levels and favorable clinical parame ters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high MAMA levels than in patients wit h lower MAMA levels, even when the sub-group of non-responder patients was considered. Evaluation of the anti-idiotypic response in MAMA-positive sera indicated that 11/17 sera showed high-titer (>6000) binding of OC/TR, as e valuated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifica lly inhibited the binding of the MOv18 and anti-CD3 parental MAbs to ovaria n-carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated f or duration of the MAMA response, 5 showed stable or even increased MAMA le vels. The long-lasting MAMA response maintained an anti-idiotypic component , directed mainly against the alpha CD3 idiotype of bi-MAb OC/TR in 2 out o f 3 cases tested. (C) 1999 Wiley-Liss, Inc.