PMID- 7557620
OWN - NLM
STAT- MEDLINE
DCOM- 19951027
LR  - 20061115
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 59
IP  - 1
DP  - 1995 Oct
TI  - Targeted eradication of ovarian cancer mediated by intracellular expression of 
      anti-erbB-2 single-chain antibody.
PG  - 8-14
AB  - OBJECTIVE: Overexpression of the tyrosine kinase receptor erbB-2 is important in 
      the pathogenesis of a variety of neoplasms including ovarian cancer. As a 
      strategy to selectively eradicate erbB-2-overexpressing tumor cells, an 
      anti-erbB-2 single-chain immunoglobin (sFv) gene was constructed to direct 
      expression of intracellular anti-erbB-2 antibody. The purpose of this study is to 
      establish the antitumorigenicity of this strategy in in vitro and in vivo models. 
      METHODS: An anti-erbB-2 sFv construct containing an endoplasmic reticulum 
      (ER)-directed leader sequence was transiently expressed in the human ovarian 
      carcinoma cell line SKOV3 using the adenovirus-polylysine vector. SKOV3 cells 
      transfected with a non-ER form of an anti-erbB-2 sFv construct or an irrelevant 
      plasmid DNA served as controls. Antitumorigenicity, as measured by 
      anchorage-independent growth in soft agar and subcutaneous (sc) tumor formation, 
      was analyzed. The ability to achieve a biological effect with relevant sFv in 
      murine orthotopic xenograft models and in primary human ovarian cancer cells was 
      also evaluated. RESULTS: The ER form of anti-erbB-2 sFv was found to exert a 
      marked antineoplastic effect on the SKOV3 cell line resulting in an arrest of 
      anchorage-independent growth. A significant increase in sc tumor volume was noted 
      in animals challenged with control constructs. In marked contrast, complete tumor 
      eradication was noted at necropsy 80 days after sc transplantation in the group 
      challenged with the ER-directed anti-erbB-2 sFv gene. Intraperitoneal treatment 
      of malignant ascites in human tumor xenograft models with the ER form of the 
      anti-erbB-2 sFv gene resulted in profound downregulation of cell surface erbB-2 
      in retrieved ovarian cancer cells. The ER-directed anti-erbB-2 sFv also elicited 
      a significant cytotoxic effect in transfected primary ovarian cancer cells 
      obtained from a patient with malignant ascites. CONCLUSION: The ability to 
      selectively "knock out" erbB-2 demonstrates that this strategy can induce a 
      significant antineoplastic effect in ovarian cancer cells overexpressing this 
      growth factor receptor. In addition, the ability to accomplish selective 
      abrogation of erbB-2 expression in animal treatment models and to transfect and 
      eradicate primary ovarian cancer cells justifies further investigation of this 
      novel strategy in ovarian cancer patients.
FAU - Deshane, J
AU  - Deshane J
AD  - Gene Therapy Program, University of Alabama at Birmingham 35233, USA.
FAU - Cabrera, G
AU  - Cabrera G
FAU - Grim, J E
AU  - Grim JE
FAU - Siegal, G P
AU  - Siegal GP
FAU - Pike, J
AU  - Pike J
FAU - Alvarez, R D
AU  - Alvarez RD
FAU - Curiel, D T
AU  - Curiel DT
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Antibodies)
RN  - 0 (Immunoglobulin Fragments)
SB  - IM
CIN - Gynecol Oncol. 1995 Oct;59(1):6-7. PMID: 7557617
MH  - Animals
MH  - Antibodies/*therapeutic use
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Genes, erbB-2/*genetics/immunology
MH  - Humans
MH  - Immunoglobulin Fragments/immunology
MH  - Immunotherapy/methods
MH  - Mice
MH  - Ovarian Neoplasms/genetics/*therapy
MH  - Tumor Cells, Cultured
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - S0090-8258(85)71260-7 [pii]
AID - 10.1006/gyno.1995.1260 [doi]
PST - ppublish
SO  - Gynecol Oncol. 1995 Oct;59(1):8-14. doi: 10.1006/gyno.1995.1260.