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Lieping Chen

Publications and source records attributed to Lieping Chen.

93 records · Page 6Linked to original sources

Immunoglobulin fusion proteins as a tool for evaluation of T-cell costimulatory molecules.

Costimulatory signal(s) in addition to engagement of T cell receptor is important for optimal activation of T lymphocytes. During last decade several dozens of new costimulatory molecules, including 4-1BB, CD40, OX40, CD27, and ICOS, have been identified. It is likely that in Post-Genome Era more molecules with potential costimulatory properties will be brought to our attention. We describe here a simple and reliable strategy for evaluating the functional activities of potential costimulatory molecules using soluble fusion protein between extracellular portion of costimulatory ligand and Fc portion of mouse IgG2a.

Animals↗

Interleukin 4 receptor-directed cytotoxin therapy for human head and neck squamous cell carcinoma in animal models.

Receptors for interleukin 4 (IL-4R) are overexpressed on the surface of various human solid tumors including renal cell carcinoma, glioblastoma, Kaposi's sarcoma, and head and neck squamous cell carcinoma (SCCHN). On the basis of this preferential receptor overexpression, a novel IL-4R-targeted cytotoxin, IL-4 (38-37)-PE38KDEL, was developed in which circularly permuted IL-4 [IL-4 (38-37)] was fused to mutated form of Pseudomonas exotoxin (PE38KDEL). Despite the recognized expression of the IL-4R on SSCHN, the utility of a receptor-specific fusion protein for the treatment of this disease remains unknown. The purpose of this study was to establish the utility of IL-4 (38-37)-PE38KDEL for the treatment of established SSCHN in animal models of human disease. Expression of IL-4R in SCCHN was confirmed by immunohistochemistry with eight of eight tissue sections expressing IL-4R. Protein synthesis inhibition assays demonstrated growth inhibition of two cell lines in IL-4 (38-37)-PE38KDEL in a dose-dependent fashion. In two SCCHN s.c. xenografted nude mouse models, i.p. and intratumoral injection of IL-4 (38-37)-PE38KDEL mediated tumor regression with no visual toxicity observed in any of the animals. Subcultured tumor cells after intratumoral treatment with IL-4 toxin did not develop resistance to the drug. These data demonstrate that IL-4 (38-37)-PE38KDEL is effective in mediating significant antitumor effects in SCCHN and may represent an attractive therapeutic option for patients with advanced cancers of the upper aerodigestive tract.

Adult↗

[Antitumor immunity elicited by 4-1BBL gene transfected Hepa1-6 in vivo].

OBJECTIVE: To study the effects of 4-1BBL on antitumor immunity induced in vivo by murine 4-1BBL gene transfected Hepa1-6. METHODS: Retrovirus vector was used to transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line Hepa1-6. The products were termed as Hepa1-6/4-1BBL, and then the TCV4-1BBL was obtained by treating them with mitomycin (MMC). Three models (immunological model, early model, and later model) were established to study the antitumor effects of TCV4-1BBL. RESULTS: (1)In immunological models, the syngeneic mice were completely protected by inoculation with TCV4-1BBL, survived free from tumor for a long period (over 100 days). (2)In early models (7 days after inoculation), Hepa1-6 tumor cells showed strong immunogenicity effects and (3) In later models (14 days after inoculation), they had obvious antitumor effects and most of the tumors were disappeared. CONCLUSIONS: The antitumor effect against syngeneic murine hepatocellular carcinoma in vivo is obviously enhanced by treating them with TCV4-1BBL

4-1BB Ligand↗