Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47? combination therapy against glioblastoma

被引：36

作者：

Chalise, Lushun ^{[1
,2
,3
]}

Kato, Akira

Ohno, Masasuke ^{[4
]}

Maeda, Sachi ^{[1
]}

Yamamichi, Akane ^{[5
]}

Kuramitsu, Shunichiro ^{[6
]}

Shiina, Satoshi ^{[7
]}

Takahashi, Hiromi ^{[8
]}

Ozone, Sachiko

Yamaguchi, Junya ^{[1
]}

Kato, Yukinari ^{[9
,10
]}

Rockenbach, Yumi ^{[11
]}

Natsume, Atsushi ^{[11
,12
,14
]}

Todo, Tomoki ^{[3
,13
]}

机构：

[1] Nagoya Univ, Dept Neurosurg, Sch Med, Nagoya, Japan

[2] Nagoya Cent Hosp, Dept Neurosurg, Nagoya, Japan

[3] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Innovat Canc Therapy, Tokyo, Japan

[4] Aichi Canc Ctr Hosp, Dept Neurosurg, Nagoya, Japan

[5] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[6] Nagoya Med Ctr, Dept Neurosurg, Natl Hosp Org, Nagoya, Japan

[7] East Nagoya Imaging Diag Ctr, Nagoya, Japan

[8] Nagoya Univ, Grad Sch Engn, Dept Biomol Engn, Nagoya, Japan

[9] Tohoku Univ, Dept Mol Pharmacol, Grad Sch Med, Sendai, Japan

[10] Tohoku Univ, Dept Antibody Drug Dev, Grad Sch Med, Sendai, Japan

[11] Nagoya Univ, Inst Innovat Future Soc, Nagoya, Japan

[12] Kawamura Med Soc Hosp, Dept Neurosug, Gifu, Japan

[13] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Innovat Canc Ther apy, 4 6 1 Shirokanedai,Minato ku, Tokyo 1088639, Japan

[14] Nagoya Univ, Inst Innovat Future Soc, N Room 803, Furo Cho, Chikusa Ku, Nagoya 4648601, Japan

来源：

MOLECULAR THERAPY ONCOLYTICS | 2022年 / 26卷

关键词：

MONOCLONAL-ANTIBODY; ADJUVANT TEMOZOLOMIDE; MARKER; IMMUNOTHERAPY; RADIOTHERAPY; CONCOMITANT; ADENOVIRUS; TUMORS; D2-40;

D O I：

10.1016/j.omto.2022.07.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma is a devastating malignant brain tumor with a poor prognosis despite standard therapy. Podoplanin (PDPN), a type I transmembrane mucin-like glycoprotein that is overexpressed in various cancers, is a potential therapeu-tic target for the treatment of glioblastoma. We previously re-ported the efficacy of chimeric antigen receptor (CAR)-T cells using an anti-pan-PDPN monoclonal antibody (mAb; NZ-1) -based third-generation CAR in a xenograft mouse model. How-ever, NZ-1 also reacted with PDPN-expressing normal cells, such as lymphatic endothelial cells, pulmonary alveolar type I cells, and podocytes. To overcome possible on-target-off-tumor effects, we produced a cancer-specific mAb (CasMab, LpMab-2)-based CAR. LpMab-2 (Lp2) reacted with PDPN-ex-pressing cancer cells but not with normal cells. In this study, Lp2-CAR-transduced T cells (Lp2-CAR-T) specifically targeted PDPN-expressing glioma cells while sparing the PDPN-ex-pressing normal cells. Lp2-CAR-T also killed patient-derived glioma stem cells, demonstrating its clinical potential against glioblastoma. Systemic injection of Lp2-CAR-T cells inhibited the growth of a subcutaneous glioma xenograft model in immunodeficient mice. Combination therapy with Lp2-CAR-T and oncolytic virus G47D, a third-generation recombinant herpes simplex virus (HSV)-1, further inhibited the tumor growth and improved survival. These findings indicate that the combination therapy of Lp2-CAR-T cells and G47D may be a promising approach to treat glioblastoma.

引用

页码：265 / 274

页数：10

共 43 条

[1] Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma [J].

Abramson, Jeremy S. ;

McGree, Brianne ;

Noyes, Sarah ;

Plummer, Sean ;

Wong, Curtis ;

Chen, Yi-Bin ;

Palmer, Edwin ;

Albertson, Tina ;

Ferry, Judith A. ;

Arrillaga-Romany, Isabel C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (08) :783-784

[2] HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma A Phase 1 Dose-Escalation Trial [J].

Ahmed, Nabil ;

Brawley, Vita ;

Hegde, Meenakshi ;

Bielamowicz, Kevin ;

Kalra, Mamta ;

Landi, Daniel ;

Robertson, Catherine ;

Gray, Tara L. ;

Diouf, Oumar ;

Wakefield, Amanda ;

Ghazi, Alexia ;

Gerken, Claudia ;

Yi, Zhongzhen ;

Ashoori, Aidin ;

Wu, Meng-Fen ;

Liu, Hao ;

Rooney, Cliona ;

Dotti, Gianpietro ;

Gee, Adrian ;

Su, Jack ;

Kew, Yvonne ;

Baskin, David ;

Zhang, Yi Jonathan ;

New, Pamela ;

Grilley, Bambi ;

Stojakovic, Milica ;

Hicks, John ;

Powell, Suzanne Z. ;

Brenner, Malcolm K. ;

Heslop, Helen E. ;

Grossman, Robert ;

Wels, Winfried S. ;

Gottschalk, Stephen .

JAMA ONCOLOGY, 2017, 3 (08) :1094-1101

[3] Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma [J].

Ahmed, Nabil ;

Brawley, Vita S. ;

Hegde, Meenakshi ;

Robertson, Catherine ;

Ghazi, Alexia ;

Gerken, Claudia ;

Liu, Enli ;

Dakhova, Olga ;

Ashoori, Aidin ;

Corder, Amanda ;

Gray, Tara ;

Wu, Meng-Fen ;

Liu, Hao ;

Hicks, John ;

Rainusso, Nino ;

Dotti, Gianpietro ;

Mei, Zhuyong ;

Grilley, Bambi ;

Gee, Adrian ;

Rooney, Cliona M. ;

Brenner, Malcolm K. ;

Heslop, Helen E. ;

Wels, Winfried S. ;

Wang, Lisa L. ;

Anderson, Peter ;

Gottschalk, Stephen .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15) :1688-+

[4] CAR T cells for brain tumors: Lessons learned and road ahead [J].

Akhavan, David ;

Alizadeh, Darya ;

Wang, Dongrui ;

Weist, Michael R. ;

Shepphird, Jennifer K. ;

Brown, Christine E. .

IMMUNOLOGICAL REVIEWS, 2019, 290 (01) :60-84

[5] CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges [J].

Bagley, Stephen J. ;

Desai, Arati S. ;

Linette, Gerald P. ;

June, Carl H. ;

O'Rourke, Donald M. .

NEURO-ONCOLOGY, 2018, 20 (11) :1429-1438

[6] Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy [J].

Brown, Christine E. ;

Alizadeh, Darya ;

Starr, Renate ;

Weng, Lihong ;

Wagner, Jamie R. ;

Naranjo, Araceli ;

Ostberg, Julie R. ;

Blanchard, M. Suzette ;

Kilpatrick, Julie ;

Simpson, Jennifer ;

Kurien, Anita ;

Priceman, Saul J. ;

Wang, Xiuli ;

Harshbarger, Todd L. ;

D'Apuzzo, Massimo ;

Ressler, Julie A. ;

Jensen, Michael C. ;

Barish, Michael E. ;

Chen, Mike ;

Portnow, Jana ;

Forman, Stephen J. ;

Badie, Behnam .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (26) :2561-2569

[7] Oncolytic Viruses and Their Application to Cancer Immunotherapy [J].

Chiocca, E. Antonio ;

Rabkin, Samuel D. .

CANCER IMMUNOLOGY RESEARCH, 2014, 2 (04) :295-300

[8] Chimeric antigen receptor T-cell immunotherapy for glioblastoma: practical insights for neurosurgeons [J].

Choi, Bryan D. ;

Curry, William T. ;

Carter, Bob S. ;

Maus, Marcela, V .

NEUROSURGICAL FOCUS, 2018, 44 (06)

[9] Genetically Engineered T-Cells for Malignant Glioma: Overcoming the Barriers to Effective Immunotherapy [J].

Chuntova, Pavlina ;

Downey, Kira M. ;

Hegde, Bindu ;

Almeida, Neil D. ;

Okada, Hideho .

FRONTIERS IN IMMUNOLOGY, 2019, 9

[10] Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions [J].

Curran, Kevin J. ;

Pegram, Hollie J. ;

Brentjens, Renier J. .

JOURNAL OF GENE MEDICINE, 2012, 14 (06) :405-415

← 1 2 3 4 5 →