Isolation of Human Fab Fragments Against Ovarian Carcinoma Using Guided Selection
Ovarian cancer remains a major health problem in the United States and most Western European countries. Despite the availability of several effective chemotherapeutic agents for the treatment of ovarian cancer, survival is still poor. Major problems in ovarian cancer chemotherapies are a failure to consolidate response, acquired/intrinsic drug resistance, and dose-limiting toxicity. Thus new therapeutic treatment modalities have been developed, most of which are based on the targeting ability of monoclonal antibodies ( MAbs) that detect tumor-associated antigens. After early disappointments, some relevant clinical success has recently been achieved, and several alternative and/ or supplementary approaches are being explored. For detailed information on aspects such as mechanisms of action, preclinical screening, and clinical results, see specific references in Table 1 and an excellent recent review (1 ). Table 1 Target Antigens Potentially Suited for Antibody-Based Immunotherapy of Ovarian Carcinoma a
Target antigen overexpressed by | Antibody entered into clinicb | Product type | Type of therapy | Trial status | References |
Ovarian and few other carcinomas | |||||
FR c (a isoform) | MOV 18 | Murine | Radioimmunotherapy | I/II | (22) |
Murine-bispecific | CTL retargeting | I/II | (23) | ||
Chimeric | Radioimmunotherapy | I/II | (24) | ||
Ca-125 | B43. 13 (OVAREX) | Murine | Naked Ab | II/III | (25) |
OC-125 | Murine | Radioimmunotherapy | I/II | (26) | |
Ovarian and many other carcinomas | |||||
HER2/neu | Trastuzumab | Humanized | Naked Ab | I/II | (27) |
(HERCEPTIN) d | |||||
PEM/MUCl | HMFG-l (THERAGYN) | Murine | Radioimmunotherapy | III | (28) |
hCTMOl | Chimeric | Radioimmunotherapy | I | (29) | |
CEA | MN-14 | Murine | Radioimmunotherapy | I | (30,31) |
TAG-72 | B72. 3 | Murine | Radioimmunotherapy | I/II | (32) |
CC49 | Murine | Radioimmunotherapy | I/II | (33) | |
Not defined | 88BV59 (HUMARAD) | Human | Radioimmunotherapy | I/II |
a For details on target antigen characteristics and biodistribution and rationale for therapeutic approach, see specific references cited in the clinical trial reports. For trial status, see also individual company websites. b In parenthesis the commercial name of the reagent. c FR, folate receptor; PEM/MUC1, polymorphic epithelial mucin, product of MUC1 gene; CEA, carcinoembryonic antigen. d FDA-approved (1998) for metastatizing breast tumors; phase III for early breast cancer tumors.