Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma

Chrystal U. Louis, Barbara Savoldo, Gianpietro Dotti, Martin Pule, Eric Yvon, G. Doug Myers, Claudia Rossig, Heidi V. Russell, Oumar Diouf, Enli Liu, Hao Liu, Meng Fen Wu, Adrian P. Gee, Zhuyong Mei, Cliona M. Rooney, Helen E. Heslop, Malcolm K. Brenner

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474 Citations (Scopus)

Abstract

We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBVCTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the longterm clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome.We observed persistence for up to 192 weeks for CARATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4 + cells and central memory cells (CD45RO + CD62L + ) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.

Original languageEnglish (US)
Pages (from-to)6050-6056
Number of pages7
JournalBlood
Volume118
Issue number23
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

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Antigen Receptors
T-cells
T-Cell Antigen Receptor
Neuroblastoma
Tumors
Cytotoxic T-Lymphocytes
Human Herpesvirus 4
Neoplasms
T-Lymphocytes
Antigens
Survival
Cells
Data storage equipment

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Louis, C. U., Savoldo, B., Dotti, G., Pule, M., Yvon, E., Myers, G. D., ... Brenner, M. K. (2011). Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood, 118(23), 6050-6056. https://doi.org/10.1182/blood-2011-05-354449

Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. / Louis, Chrystal U.; Savoldo, Barbara; Dotti, Gianpietro; Pule, Martin; Yvon, Eric; Myers, G. Doug; Rossig, Claudia; Russell, Heidi V.; Diouf, Oumar; Liu, Enli; Liu, Hao; Wu, Meng Fen; Gee, Adrian P.; Mei, Zhuyong; Rooney, Cliona M.; Heslop, Helen E.; Brenner, Malcolm K.

In: Blood, Vol. 118, No. 23, 01.12.2011, p. 6050-6056.

Research output: Contribution to journalArticle

Louis, CU, Savoldo, B, Dotti, G, Pule, M, Yvon, E, Myers, GD, Rossig, C, Russell, HV, Diouf, O, Liu, E, Liu, H, Wu, MF, Gee, AP, Mei, Z, Rooney, CM, Heslop, HE & Brenner, MK 2011, 'Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma', Blood, vol. 118, no. 23, pp. 6050-6056. https://doi.org/10.1182/blood-2011-05-354449
Louis, Chrystal U. ; Savoldo, Barbara ; Dotti, Gianpietro ; Pule, Martin ; Yvon, Eric ; Myers, G. Doug ; Rossig, Claudia ; Russell, Heidi V. ; Diouf, Oumar ; Liu, Enli ; Liu, Hao ; Wu, Meng Fen ; Gee, Adrian P. ; Mei, Zhuyong ; Rooney, Cliona M. ; Heslop, Helen E. ; Brenner, Malcolm K. / Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. In: Blood. 2011 ; Vol. 118, No. 23. pp. 6050-6056.
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AU - Savoldo, Barbara

AU - Dotti, Gianpietro

AU - Pule, Martin

AU - Yvon, Eric

AU - Myers, G. Doug

AU - Rossig, Claudia

AU - Russell, Heidi V.

AU - Diouf, Oumar

AU - Liu, Enli

AU - Liu, Hao

AU - Wu, Meng Fen

AU - Gee, Adrian P.

AU - Mei, Zhuyong

AU - Rooney, Cliona M.

AU - Heslop, Helen E.

AU - Brenner, Malcolm K.

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