Immune responses to murine monoclonal antibody-B43.13 correlate with prolonged survival of women with recurrent ovarian cancer.
OBJECTIVE
We evaluated the therapeutic efficiency of the murine monoclonal antibody-B43.13 in the treatment of patients with recurrent ovarian cancer.


METHODS
This was a retrospective study of immune responses and survival in 44 patients who were treated with technetium 99m-labeled monoclonal antibody-B43.13, a murine monoclonal antibody that is directed against the tumor-associated antigen CA125. Most patients were pretreated heavily. Biologic activity was quantified by the assay of immune responses to the human anti-murine antibodies against the monoclonal antibody-B43.13 variable region (Ab(2)) and antibodies that target the CA 125 antigen itself (anti-CA 125 antibody).


RESULTS
More than one half of patients (56.8%) survived for >12 months after the first dose of monoclonal antibody B43.13; 34.1% of the patients survived >24 months. To date, 6 of the 44 patients are alive, with survival times of 4 to 7.5 years after the start of the antibody treatment. More than 60% of the evaluable patients met predefined criteria for robust, treatment-emergent human anti-murine antibodies and Ab(2) responses, and these responses were associated with improved survival rates. Median survival time increased approximately 3-fold for human anti-murine antibody responders (22.6 months) versus nonresponders (7.2 months; P <.0016, log-rank test) and 2-fold for Ab(2) responders (18.3 months) versus nonresponders (9.3 months). No serious drug-associated adverse events were reported.


CONCLUSIONS
The associations between multiple types of immune response and improved clinical outcomes suggest that monoclonal antibody-B43.13 should be further evaluated for potential use as an immunotherapy for CA125-expressing malignancies.
Möbus
Volker J
VJ
Department of Obstetrics and Gynecology, Städtische Kliniken, Frankfurt, Germany. MoebusVolk@aol.com
Baum
Richard P
RP
Bolle
Marcus
M
Kreienberg
Rolf
R
Noujaim
Antoine A
AA
Schultes
Birgit C
BC
Nicodemus
Christopher F
CF
D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000276:immunology*; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D013667:Technetium
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D013667:Technetium