Author: Shih, Jin-Yuan ; Wu, Cheng-Wen ; Kao, Yu-Rong ; Chen, Bing-Mae ; Chu, Yi-Wen ; Ko, Ya-Ping ; Roffler, Steve R ; Yang, Pan-Chyr ; Wen, Wei-Chun ; Chan, Yi-Lin

Metastasis is a coordinated process that depends on the interaction of cancer cells with the tumor microenvironment. Members of the transmembrane-4 superfamily (TM4SF) of surface proteins have been implicated in the regulation of cancer cell metastasis, and the expression of several TM4SF members on tumor cells is inversely correlated with patient prognosis. The tumor-associated antigen L6 (TAL6), a distant member of the TM4SF, is expressed on most epithelial cell carcinomas and is a target for antibody-mediated therapy. We examined whether TAL6 may play a role in cancer metastasis by using an established series of human lung carcinoma cell lines (CL1-0 to CL1-5) that exhibit increasing invasiveness in vitro and in vivo. We found that TAL6 expression correlated with the in vitro invasiveness of CL lung carcinoma cells (r(2) = 0.98) and human carcinoma cells (r(2) = 0.69). Forced expression of TAL6 on CL1-0 lung carcinoma cells significantly increased their in vitro invasiveness and decreased the survival of SCID mice in an experimental metastasis model. Specific antibody against TAL6 (monoclonal antibody L6) significantly reduced the migration and invasiveness of CL1-5 lung carcinoma cells. The effects of monoclonal antibody L6 on CL1-5 invasion required clustering of TAL6 on the cell surface. Real-time reverse transcription-PCR of lung cancer specimens showed that increased expression of TAL6 was significantly associated with early postoperative relapse (P = 0.034) and shorter survival (P = 0.025) in squamous cell lung cancer patients. Thus, TAL6 appears to be involved in cancer invasion and metastasis.

01 Aug 2000·The ProstateQ3 · MEDICINE

Efficacy and toxicity of radioimmunotherapy with90Y-DOTA-peptide-ChL6 for PC3-tumored mice

Q3 · MEDICINE

Article

Author: Lamborn, Kathleen R. ; Meyers, Frederick J. ; DeNardo, Gerald L. ; Kukis, David L. ; DeNardo, Sally J. ; O'Donnell, Robert T. ; Miers, Laird

BACKGROUNDRadioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients.METHODSPharmacokinetics, blood counts, body weight, and antitumor activity of RIT with (90)yttrium-((90)Y)-DOTA-peptide-ChL6 (75-260 microCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts.RESULTSRIT produced durable, dose-dependent antitumor effects with a 100% response rate using 112 microCi and 150 microCi (the maximum tolerated dose) of (90)Y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting, and dose-related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150-microCi group survived the 84-day study period vs. 1/8 (13%) for untreated, tumored control mice.CONCLUSIONS(90)Y-DOTA-peptide-ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer.

01 Oct 1998·The ProstateQ3 · MEDICINE

L6 monoclonal antibody binds prostate cancer

Q3 · MEDICINE

Article

Author: Sally J. DeNardo ; Xu Bao Shi ; Frederick J Meyers ; Robert T O'Donnell ; Linda A. Kroger ; Gerald L Denardo ; Gary R. Mirick

BACKGROUNDRadioimmunotherapy (RIT) is a promising new modality for targeted, systemic delivery of radionuclides specifically to sites of androgen-independent metastatic prostate cancer. To be effective, RIT requires an antibody with specificity for malignant cells and appropriate pharmacokinetics in the body.METHODSSpecific binding of the L6 monoclonal antibody to prostate cancer cell lines or cell lysates was determined by enzyme-linked immunoabsorbent assay (ELISA), solid-phase radioimmunoassay, and immunofluorescent staining. Biodistribution, tumor uptake, and whole body and blood clearances of 125I-L6 were determined in nude mice bearing human prostate cancer xenografts.RESULTSThe L6 monoclonal antibody showed strong binding to the lysates of PC3 and DU145 prostate cancer cell lines, and 66% binding to live PC3 cells. The L6 antibody specifically targeted prostate cancer in PC3 and DU145-tumored nude mice, where approximately 10% of the injected dose of 125I-L6 bound to prostate cancer. Low-normal organ uptake was found, and the blood clearances were similar in each group of tumored mice.CONCLUSIONSThe L6 monoclonal antibody targets human prostate cancer xenografts in nude mice and has low-normal organ uptake. Therefore, further study of the radiolabeled L6 monoclonal antibody for RIT of prostate cancer is warranted.

100 Deals associated with Monoclonal antibody L6(Bristol Myers Squibb)

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 1	United States	-	-
Neoplasms	Phase 1	-	Bristol Myers Squibb Co.	-

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