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Differential cytopathology and kinetics of measles oncolysis in T=two primary B-cell malignancies provides mechanistic insights

Differential cytopathology and kinetics of measles oncolysis in T=two primary B-cell malignancies provides mechanistic insights
Differential cytopathology and kinetics of measles oncolysis in T=two primary B-cell malignancies provides mechanistic insights
Clinical trials using vaccine measles virus (MV) as anticancer therapy are already underway. We compared the oncolytic potential of MV in two B-cell malignancies; adult acute lymphoblastic leukemia (ALL, an aggressive leukemia) and chronic lymphocytic leukemia (CLL, an indolent leukemia overexpressing Bcl-2) using patient-derived material. In vitro, distinct cytopathological effects were observed between MV-infected primary ALL and CLL cells, with large multinucleated syncytia forming in ALL cultures compared to minimal cell-to-cell fusion in infected CLL cells. Cell viability and immunoblotting studies confirmed rapid cell death in MV-infected ALL cultures and slower MV oncolysis of CLL cells. In cell lines, overexpression of Bcl-2 diminished MV-induced cell death providing a possible mechanism for the slower kinetic of MV oncolysis in CLL. In vivo, intratumoral MV treatment of established subcutaneous ALL xenografts had striking antitumor activity leading to complete resolution of all tumors. The antitumor activity of MV was also evident in disseminated ALL xenograft models. In summary, both ALL and CLL are targets for MV-mediated lysis albeit with different kinetics. The marked sensitivity of both primary ALL cells and ALL xenografts to MV oncolysis highlights the tremendous potential of MV as a novel replicating-virus therapy for adult ALL
1525-0016
1034-1040
Patel, Bella
68da30b0-4add-4612-a1f7-48e8773bdd83
Dey, Aditi
36f05b9b-a33b-473c-8968-0e925c0446b8
Ghorani, Ehsan
4dfd1d77-5b23-477f-8d54-21ec52220f5e
Kumar, Shaji
8127c1c9-c1f4-4574-b316-bad4529cddac
Malam, Yogeshkumar
271b4e22-3be8-4e36-8d3e-1ed9290a2108
Rai, Lena
e72e9a5d-af68-4ab8-a4f2-d8b88efac08b
Steele, Andrew J.
4349f6aa-2e3a-49a8-be73-7716056ae089
Thomson, Jennifer
3209adc8-4863-4f55-993d-494a92435549
Wickremasinghe, R. Gitendra
6a90cc2b-8db5-45c2-ab57-7a1341b88bb2
Zhang, Yu
9b5536fe-d7c1-40a1-b3f5-c0cc6f0724e7
Castleton, Anna Z.
b6903a2a-bd01-489b-970a-a32be69caa7a
Fielding, Adele K.
f1a331a0-d040-4dae-84ca-5234cc0f9375
Patel, Bella
68da30b0-4add-4612-a1f7-48e8773bdd83
Dey, Aditi
36f05b9b-a33b-473c-8968-0e925c0446b8
Ghorani, Ehsan
4dfd1d77-5b23-477f-8d54-21ec52220f5e
Kumar, Shaji
8127c1c9-c1f4-4574-b316-bad4529cddac
Malam, Yogeshkumar
271b4e22-3be8-4e36-8d3e-1ed9290a2108
Rai, Lena
e72e9a5d-af68-4ab8-a4f2-d8b88efac08b
Steele, Andrew J.
4349f6aa-2e3a-49a8-be73-7716056ae089
Thomson, Jennifer
3209adc8-4863-4f55-993d-494a92435549
Wickremasinghe, R. Gitendra
6a90cc2b-8db5-45c2-ab57-7a1341b88bb2
Zhang, Yu
9b5536fe-d7c1-40a1-b3f5-c0cc6f0724e7
Castleton, Anna Z.
b6903a2a-bd01-489b-970a-a32be69caa7a
Fielding, Adele K.
f1a331a0-d040-4dae-84ca-5234cc0f9375

Patel, Bella, Dey, Aditi, Ghorani, Ehsan, Kumar, Shaji, Malam, Yogeshkumar, Rai, Lena, Steele, Andrew J., Thomson, Jennifer, Wickremasinghe, R. Gitendra, Zhang, Yu, Castleton, Anna Z. and Fielding, Adele K. (2011) Differential cytopathology and kinetics of measles oncolysis in T=two primary B-cell malignancies provides mechanistic insights. Molecular Therapy, 19 (6), 1034-1040. (doi:10.1038/mt.2011.44). (PMID:21427708)

Record type: Article

Abstract

Clinical trials using vaccine measles virus (MV) as anticancer therapy are already underway. We compared the oncolytic potential of MV in two B-cell malignancies; adult acute lymphoblastic leukemia (ALL, an aggressive leukemia) and chronic lymphocytic leukemia (CLL, an indolent leukemia overexpressing Bcl-2) using patient-derived material. In vitro, distinct cytopathological effects were observed between MV-infected primary ALL and CLL cells, with large multinucleated syncytia forming in ALL cultures compared to minimal cell-to-cell fusion in infected CLL cells. Cell viability and immunoblotting studies confirmed rapid cell death in MV-infected ALL cultures and slower MV oncolysis of CLL cells. In cell lines, overexpression of Bcl-2 diminished MV-induced cell death providing a possible mechanism for the slower kinetic of MV oncolysis in CLL. In vivo, intratumoral MV treatment of established subcutaneous ALL xenografts had striking antitumor activity leading to complete resolution of all tumors. The antitumor activity of MV was also evident in disseminated ALL xenograft models. In summary, both ALL and CLL are targets for MV-mediated lysis albeit with different kinetics. The marked sensitivity of both primary ALL cells and ALL xenografts to MV oncolysis highlights the tremendous potential of MV as a novel replicating-virus therapy for adult ALL

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Published date: 22 March 2011
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 178439
URI: http://eprints.soton.ac.uk/id/eprint/178439
ISSN: 1525-0016
PURE UUID: fa90cf3d-e741-4819-9a67-ffa886443f51
ORCID for Andrew J. Steele: ORCID iD orcid.org/0000-0003-0667-1596

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Date deposited: 28 Mar 2011 09:01
Last modified: 18 Feb 2021 17:16

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Contributors

Author: Bella Patel
Author: Aditi Dey
Author: Ehsan Ghorani
Author: Shaji Kumar
Author: Yogeshkumar Malam
Author: Lena Rai
Author: Jennifer Thomson
Author: R. Gitendra Wickremasinghe
Author: Yu Zhang
Author: Anna Z. Castleton
Author: Adele K. Fielding

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