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Isolation of Human Fab Fragments Against Ovarian Carcinoma Using Guided Selection

2025-03-19 细胞技术 加入收藏
Ovarian cancer remains a major health problem in the United States and most West

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.


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