Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents

David C. Fritzinger; Brian E. Hew; June Q. Lee; James Newhouse; Maqsudul Alam; John R. Ciallella; Mallory Bowers; William B. Gorsuch; Benjamin J. Guikema; Gregory L. Stahl; Carl Wilhelm Vogel

doi:10.1007/978-0-387-78952-1_21

Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents

David C. Fritzinger, Brian E. Hew, June Q. Lee, James Newhouse, Maqsudul Alam, John R. Ciallella, Mallory Bowers, William B. Gorsuch, Benjamin J. Guikema, Gregory L. Stahl, Carl Wilhelm Vogel

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

13 Scopus citations

Abstract

To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-chain of human C3 is exchanged with homologous regions of the C-terminus of the β -chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.

Original language	English
Title of host publication	Current Topics in Complement II
Publisher	Springer New York
Pages	293-307
Number of pages	15
ISBN (Print)	9780387789514
DOIs	https://doi.org/10.1007/978-0-387-78952-1_21
State	Published - 2008
Externally published	Yes

Publication series

Name	Advances in Experimental Medicine and Biology
Volume	632
ISSN (Print)	0065-2598

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10.1007/978-0-387-78952-1_21

Cite this

Fritzinger, D. C., Hew, B. E., Lee, J. Q., Newhouse, J., Alam, M., Ciallella, J. R., Bowers, M., Gorsuch, W. B., Guikema, B. J., Stahl, G. L., & Vogel, C. W. (2008). Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents. In Current Topics in Complement II (pp. 293-307). (Advances in Experimental Medicine and Biology; Vol. 632). Springer New York. https://doi.org/10.1007/978-0-387-78952-1_21

@inbook{9f452d2128d24fce807846e4ef270d86,

title = "Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents",

abstract = "To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-chain of human C3 is exchanged with homologous regions of the C-terminus of the β -chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.",

author = "Fritzinger, \{David C.\} and Hew, \{Brian E.\} and Lee, \{June Q.\} and James Newhouse and Maqsudul Alam and Ciallella, \{John R.\} and Mallory Bowers and Gorsuch, \{William B.\} and Guikema, \{Benjamin J.\} and Stahl, \{Gregory L.\} and Vogel, \{Carl Wilhelm\}",

note = "Funding Information: Part of the research was supported by Incode Biopharmaceutics Corporation, Lahaina, Hawaii, USA.",

year = "2008",

doi = "10.1007/978-0-387-78952-1\_21",

language = "English",

isbn = "9780387789514",

series = "Advances in Experimental Medicine and Biology",

publisher = "Springer New York",

pages = "293--307",

booktitle = "Current Topics in Complement II",

address = "United States",

}

Fritzinger, DC, Hew, BE, Lee, JQ, Newhouse, J, Alam, M, Ciallella, JR, Bowers, M, Gorsuch, WB, Guikema, BJ, Stahl, GL & Vogel, CW 2008, Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents. in Current Topics in Complement II. Advances in Experimental Medicine and Biology, vol. 632, Springer New York, pp. 293-307. https://doi.org/10.1007/978-0-387-78952-1_21

Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents. / Fritzinger, David C.; Hew, Brian E.; Lee, June Q. et al.
Current Topics in Complement II. Springer New York, 2008. p. 293-307 (Advances in Experimental Medicine and Biology; Vol. 632).

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

TY - CHAP

T1 - Derivatives of human complement component C3 for therapeutic complement depletion

T2 - A novel class of therapeutic agents

AU - Fritzinger, David C.

AU - Hew, Brian E.

AU - Lee, June Q.

AU - Newhouse, James

AU - Alam, Maqsudul

AU - Ciallella, John R.

AU - Bowers, Mallory

AU - Gorsuch, William B.

AU - Guikema, Benjamin J.

AU - Stahl, Gregory L.

AU - Vogel, Carl Wilhelm

N1 - Funding Information: Part of the research was supported by Incode Biopharmaceutics Corporation, Lahaina, Hawaii, USA.

PY - 2008

Y1 - 2008

N2 - To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-chain of human C3 is exchanged with homologous regions of the C-terminus of the β -chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.

AB - To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-chain of human C3 is exchanged with homologous regions of the C-terminus of the β -chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.

UR - https://www.scopus.com/pages/publications/58149354314

U2 - 10.1007/978-0-387-78952-1_21

DO - 10.1007/978-0-387-78952-1_21

M3 - Chapter

C2 - 19025130

AN - SCOPUS:58149354314

SN - 9780387789514

T3 - Advances in Experimental Medicine and Biology

SP - 293

EP - 307

BT - Current Topics in Complement II

PB - Springer New York

ER -

Derivatives of human complement component C3 for therapeutic complement depletion: A novel class of therapeutic agents

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