CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma.

Shruti Bhatt, Brittany M. Ashlock, Yasodha Natkunam, Victoria Sujoy, Jennifer Chapman-Fredricks, Juan Carlos Ramos, Enrique A Mesri, Izidore Lossos

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.

Original languageEnglish
Pages (from-to)1233-1242
Number of pages10
JournalBlood
Volume122
Issue number7
DOIs
StatePublished - Aug 15 2013

Fingerprint

Primary Effusion Lymphoma
Tumors
Cells
Therapeutics
Bearings (structural)
Anaplastic Large-Cell Lymphoma
Cell Line
Human Herpesvirus 8
Neoplasms
cAC10-vcMMAE
Cell proliferation
Cell Cycle Checkpoints
Tumor Cell Line
Human Herpesvirus 4
Hodgkin Disease
Viruses
Microtubules
Non-Hodgkin's Lymphoma
Peptide Hydrolases
Monoclonal Antibodies

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

CD30 targeting with brentuximab vedotin : a novel therapeutic approach to primary effusion lymphoma. / Bhatt, Shruti; Ashlock, Brittany M.; Natkunam, Yasodha; Sujoy, Victoria; Chapman-Fredricks, Jennifer; Carlos Ramos, Juan; Mesri, Enrique A; Lossos, Izidore.

In: Blood, Vol. 122, No. 7, 15.08.2013, p. 1233-1242.

Research output: Contribution to journalArticle

@article{4619c0a4f5d145cc8ac5f5ae5aec0c92,
title = "CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma.",
abstract = "Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.",
author = "Shruti Bhatt and Ashlock, {Brittany M.} and Yasodha Natkunam and Victoria Sujoy and Jennifer Chapman-Fredricks and {Carlos Ramos}, Juan and Mesri, {Enrique A} and Izidore Lossos",
year = "2013",
month = "8",
day = "15",
doi = "10.1182/blood-2013-01-481713",
language = "English",
volume = "122",
pages = "1233--1242",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

TY - JOUR

T1 - CD30 targeting with brentuximab vedotin

T2 - a novel therapeutic approach to primary effusion lymphoma.

AU - Bhatt, Shruti

AU - Ashlock, Brittany M.

AU - Natkunam, Yasodha

AU - Sujoy, Victoria

AU - Chapman-Fredricks, Jennifer

AU - Carlos Ramos, Juan

AU - Mesri, Enrique A

AU - Lossos, Izidore

PY - 2013/8/15

Y1 - 2013/8/15

N2 - Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.

AB - Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.

UR - http://www.scopus.com/inward/record.url?scp=84887137504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887137504&partnerID=8YFLogxK

U2 - 10.1182/blood-2013-01-481713

DO - 10.1182/blood-2013-01-481713

M3 - Article

C2 - 23838350

AN - SCOPUS:84887137504

VL - 122

SP - 1233

EP - 1242

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -