The generation and anti-myeloma activity of a chimeric anti-CD54 antibody, cUV3

Joan E. Smallshaw, Elaine Coleman, Camelia Spiridon, Ellen S. Vitetta

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Despite new treatment options, including autologous and allogeneic stem cell transplants, multiple myeloma remains an incurable disease. The authors developed and characterized a murine anti-human ICAM-1 (CD54) monoclonal antibody, UV3, which is highly effective in SCID mice with advanced human myeloma xenografts (SCID/ARH-77). To improve the effector functions and pharmacokinetic parameters and to reduce its immunogenicity in humans, the authors engineered this monoclonal antibody into a mouse/human IgG1κ chimeric (c) antibody, cUV3. Following co-expression and purification of the genetically spliced heavy and light chain constructs, the authors compared cUV3 and UV3 in various in vitro assays, including relative cell-binding affinities and effector functions, namely antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The authors compared their in vivo retention times and biodistribution patterns in normal mice. In each assay, the authors found that cUV3 was essentially equivalent to UV3. Finally, these antibodies were tested in a SCID/ARH-77 model of advanced myeloma, with daily treatments of 4 μg/g for 4 consecutive days commencing 14 days after tumor cell inoculation. cUV3 was at least as effective as UV3; 40% and 20% of the mice, respectively, were cured, with no sign of disease at day 150. The authors intend to evaluate the efficacy of cUV3 further in SCID/ARH-77 mice using other doses and dosing schedules to try to improve the cure rate. Eventually, they hope to test the efficacy of cUV3 in patients with multiple myeloma.

Original languageEnglish (US)
Pages (from-to)419-424
Number of pages6
JournalJournal of Immunotherapy
Volume27
Issue number6
StatePublished - Nov 2004

Fingerprint

Anti-Idiotypic Antibodies
Multiple Myeloma
Antibodies
SCID Mice
Intercellular Adhesion Molecule-1
Heterografts
Appointments and Schedules
Stem Cells
Pharmacokinetics
Immunoglobulin G
Monoclonal Antibodies
Transplants
Light
Neoplasms
Therapeutics

Keywords

  • ADCC
  • Biodistribution
  • CD54
  • CDC
  • Chimeric antibody
  • ICAM-I
  • Multiple myeloma
  • Pharmacokinetics
  • SCID mouse tumor model

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

The generation and anti-myeloma activity of a chimeric anti-CD54 antibody, cUV3. / Smallshaw, Joan E.; Coleman, Elaine; Spiridon, Camelia; Vitetta, Ellen S.

In: Journal of Immunotherapy, Vol. 27, No. 6, 11.2004, p. 419-424.

Research output: Contribution to journalArticle

Smallshaw, JE, Coleman, E, Spiridon, C & Vitetta, ES 2004, 'The generation and anti-myeloma activity of a chimeric anti-CD54 antibody, cUV3', Journal of Immunotherapy, vol. 27, no. 6, pp. 419-424.
Smallshaw, Joan E. ; Coleman, Elaine ; Spiridon, Camelia ; Vitetta, Ellen S. / The generation and anti-myeloma activity of a chimeric anti-CD54 antibody, cUV3. In: Journal of Immunotherapy. 2004 ; Vol. 27, No. 6. pp. 419-424.
@article{a677ebd9099d472fa08d47a74cc3debb,
title = "The generation and anti-myeloma activity of a chimeric anti-CD54 antibody, cUV3",
abstract = "Despite new treatment options, including autologous and allogeneic stem cell transplants, multiple myeloma remains an incurable disease. The authors developed and characterized a murine anti-human ICAM-1 (CD54) monoclonal antibody, UV3, which is highly effective in SCID mice with advanced human myeloma xenografts (SCID/ARH-77). To improve the effector functions and pharmacokinetic parameters and to reduce its immunogenicity in humans, the authors engineered this monoclonal antibody into a mouse/human IgG1κ chimeric (c) antibody, cUV3. Following co-expression and purification of the genetically spliced heavy and light chain constructs, the authors compared cUV3 and UV3 in various in vitro assays, including relative cell-binding affinities and effector functions, namely antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The authors compared their in vivo retention times and biodistribution patterns in normal mice. In each assay, the authors found that cUV3 was essentially equivalent to UV3. Finally, these antibodies were tested in a SCID/ARH-77 model of advanced myeloma, with daily treatments of 4 μg/g for 4 consecutive days commencing 14 days after tumor cell inoculation. cUV3 was at least as effective as UV3; 40{\%} and 20{\%} of the mice, respectively, were cured, with no sign of disease at day 150. The authors intend to evaluate the efficacy of cUV3 further in SCID/ARH-77 mice using other doses and dosing schedules to try to improve the cure rate. Eventually, they hope to test the efficacy of cUV3 in patients with multiple myeloma.",
keywords = "ADCC, Biodistribution, CD54, CDC, Chimeric antibody, ICAM-I, Multiple myeloma, Pharmacokinetics, SCID mouse tumor model",
author = "Smallshaw, {Joan E.} and Elaine Coleman and Camelia Spiridon and Vitetta, {Ellen S.}",
year = "2004",
month = "11",
language = "English (US)",
volume = "27",
pages = "419--424",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - The generation and anti-myeloma activity of a chimeric anti-CD54 antibody, cUV3

AU - Smallshaw, Joan E.

AU - Coleman, Elaine

AU - Spiridon, Camelia

AU - Vitetta, Ellen S.

PY - 2004/11

Y1 - 2004/11

N2 - Despite new treatment options, including autologous and allogeneic stem cell transplants, multiple myeloma remains an incurable disease. The authors developed and characterized a murine anti-human ICAM-1 (CD54) monoclonal antibody, UV3, which is highly effective in SCID mice with advanced human myeloma xenografts (SCID/ARH-77). To improve the effector functions and pharmacokinetic parameters and to reduce its immunogenicity in humans, the authors engineered this monoclonal antibody into a mouse/human IgG1κ chimeric (c) antibody, cUV3. Following co-expression and purification of the genetically spliced heavy and light chain constructs, the authors compared cUV3 and UV3 in various in vitro assays, including relative cell-binding affinities and effector functions, namely antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The authors compared their in vivo retention times and biodistribution patterns in normal mice. In each assay, the authors found that cUV3 was essentially equivalent to UV3. Finally, these antibodies were tested in a SCID/ARH-77 model of advanced myeloma, with daily treatments of 4 μg/g for 4 consecutive days commencing 14 days after tumor cell inoculation. cUV3 was at least as effective as UV3; 40% and 20% of the mice, respectively, were cured, with no sign of disease at day 150. The authors intend to evaluate the efficacy of cUV3 further in SCID/ARH-77 mice using other doses and dosing schedules to try to improve the cure rate. Eventually, they hope to test the efficacy of cUV3 in patients with multiple myeloma.

AB - Despite new treatment options, including autologous and allogeneic stem cell transplants, multiple myeloma remains an incurable disease. The authors developed and characterized a murine anti-human ICAM-1 (CD54) monoclonal antibody, UV3, which is highly effective in SCID mice with advanced human myeloma xenografts (SCID/ARH-77). To improve the effector functions and pharmacokinetic parameters and to reduce its immunogenicity in humans, the authors engineered this monoclonal antibody into a mouse/human IgG1κ chimeric (c) antibody, cUV3. Following co-expression and purification of the genetically spliced heavy and light chain constructs, the authors compared cUV3 and UV3 in various in vitro assays, including relative cell-binding affinities and effector functions, namely antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The authors compared their in vivo retention times and biodistribution patterns in normal mice. In each assay, the authors found that cUV3 was essentially equivalent to UV3. Finally, these antibodies were tested in a SCID/ARH-77 model of advanced myeloma, with daily treatments of 4 μg/g for 4 consecutive days commencing 14 days after tumor cell inoculation. cUV3 was at least as effective as UV3; 40% and 20% of the mice, respectively, were cured, with no sign of disease at day 150. The authors intend to evaluate the efficacy of cUV3 further in SCID/ARH-77 mice using other doses and dosing schedules to try to improve the cure rate. Eventually, they hope to test the efficacy of cUV3 in patients with multiple myeloma.

KW - ADCC

KW - Biodistribution

KW - CD54

KW - CDC

KW - Chimeric antibody

KW - ICAM-I

KW - Multiple myeloma

KW - Pharmacokinetics

KW - SCID mouse tumor model

UR - http://www.scopus.com/inward/record.url?scp=7444229812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444229812&partnerID=8YFLogxK

M3 - Article

C2 - 15534485

AN - SCOPUS:7444229812

VL - 27

SP - 419

EP - 424

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 6

ER -