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 antibody (MAb) develop a humoral response against the antigen even after a single dose. Analysis of a series of 35 ovarian-cancer patients entered in phase-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) response in 31/35 (88%) patients, with high HAMA levels (> or = 150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA 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 HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub-group of non-responder patients was considered. Evaluation of the anti-idiotypic response in HAMA-positive sera indicated that 11/17 sera showed high-titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti-CD3 parental MAbs to ovarian-carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long-lasting HAMA response maintained an anti-idiotypic component, directed mainly against the alphaCD3 idiotype of bi-MAb OC/TR in 2 out of 3 cases tested.
Miotti
S
S
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
Negri
D R
DR
Valota
O
O
Calabrese
M
M
Bolhuis
R L
RL
Gratama
J W
JW
Colnaghi
M I
MI
Canevari
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology*; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D000910:Antibodies, Heterophile / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015415:Biomarkers; D005260:Female; D006801:Humans; D051379:Mice; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D011379:Prognosis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors