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A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent.

De Lorenzo C, Tedesco A, Terrazzano G, Cozzolino R, Laccetti P, Piccoli R, D'Alessio G - Br. J. Cancer (2004)

Bottom Line: A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain.This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo.Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.

ABSTRACT
A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain. Overexpression of the ErbB2 receptor is related to tumour aggressiveness and poor prognosis. This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo. Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life.

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Related in: MedlinePlus

Antibody-dependent and complement-dependent cytotoxicity assays of Erb-hcAb. (A) SKBR3 cells treated with PBL as effector cells at four different ratios: in the absence (white bars), or in the presence of Erb-hcAb (black bars). Erbicin, the parental anti-ErbB2 scFv (striped bars), and Herceptin (grey bars) were used as a negative and a positive control, respectively. (B) ErbB2-overexpressing SKBR3 cells were incubated for 2 or 6 h, in the presence of human serum as a source of complement, with Erb-hcAb at a concentration of 3 μg ml−1 (shaded bars) or 10 μg ml−1 (black bars). Herceptin (10 μg ml−1) was used as a negative control (white bars).
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fig3: Antibody-dependent and complement-dependent cytotoxicity assays of Erb-hcAb. (A) SKBR3 cells treated with PBL as effector cells at four different ratios: in the absence (white bars), or in the presence of Erb-hcAb (black bars). Erbicin, the parental anti-ErbB2 scFv (striped bars), and Herceptin (grey bars) were used as a negative and a positive control, respectively. (B) ErbB2-overexpressing SKBR3 cells were incubated for 2 or 6 h, in the presence of human serum as a source of complement, with Erb-hcAb at a concentration of 3 μg ml−1 (shaded bars) or 10 μg ml−1 (black bars). Herceptin (10 μg ml−1) was used as a negative control (white bars).

Mentions: To investigate whether Erb-hcAb was capable of recruiting immune effector functions in vitro, assays for cytolysis of tumour cells as induced by PBL, or complement, were performed. To determine the capacity of Erb-hcAb to trigger ADCC towards antigen-expressing cells, ErbB2-positive and ErbB2-negative control cells were incubated for 3 h with increasing amounts of effector PBL in the absence or in the presence of Erb-hcAb (3 μg ml−1). As shown in Figure 3AFigure 3


A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent.

De Lorenzo C, Tedesco A, Terrazzano G, Cozzolino R, Laccetti P, Piccoli R, D'Alessio G - Br. J. Cancer (2004)

Antibody-dependent and complement-dependent cytotoxicity assays of Erb-hcAb. (A) SKBR3 cells treated with PBL as effector cells at four different ratios: in the absence (white bars), or in the presence of Erb-hcAb (black bars). Erbicin, the parental anti-ErbB2 scFv (striped bars), and Herceptin (grey bars) were used as a negative and a positive control, respectively. (B) ErbB2-overexpressing SKBR3 cells were incubated for 2 or 6 h, in the presence of human serum as a source of complement, with Erb-hcAb at a concentration of 3 μg ml−1 (shaded bars) or 10 μg ml−1 (black bars). Herceptin (10 μg ml−1) was used as a negative control (white bars).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747711&req=5

fig3: Antibody-dependent and complement-dependent cytotoxicity assays of Erb-hcAb. (A) SKBR3 cells treated with PBL as effector cells at four different ratios: in the absence (white bars), or in the presence of Erb-hcAb (black bars). Erbicin, the parental anti-ErbB2 scFv (striped bars), and Herceptin (grey bars) were used as a negative and a positive control, respectively. (B) ErbB2-overexpressing SKBR3 cells were incubated for 2 or 6 h, in the presence of human serum as a source of complement, with Erb-hcAb at a concentration of 3 μg ml−1 (shaded bars) or 10 μg ml−1 (black bars). Herceptin (10 μg ml−1) was used as a negative control (white bars).
Mentions: To investigate whether Erb-hcAb was capable of recruiting immune effector functions in vitro, assays for cytolysis of tumour cells as induced by PBL, or complement, were performed. To determine the capacity of Erb-hcAb to trigger ADCC towards antigen-expressing cells, ErbB2-positive and ErbB2-negative control cells were incubated for 3 h with increasing amounts of effector PBL in the absence or in the presence of Erb-hcAb (3 μg ml−1). As shown in Figure 3AFigure 3

Bottom Line: A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain.This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo.Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.

ABSTRACT
A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain. Overexpression of the ErbB2 receptor is related to tumour aggressiveness and poor prognosis. This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo. Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life.

Show MeSH
Related in: MedlinePlus