Isolation of Human Fab Fragments Against Ovarian Carcinoma Using Guided Selection

互联网2014-02-13

718

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 clinic^b	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.