CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide.
Animals
Antibodies
/ immunology
B-Lymphocytes
/ metabolism
Humans
Immunotherapy, Adoptive
/ methods
K562 Cells
/ immunology
Male
Mice, Inbred NOD
Multiple Myeloma
/ pathology
Receptors, Antigen, T-Cell
/ immunology
Signaling Lymphocytic Activation Molecule Family
/ genetics
T-Lymphocytes
/ immunology
Xenograft Model Antitumor Assays
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 02 2020
07 02 2020
Historique:
received:
17
07
2019
accepted:
21
01
2020
entrez:
9
2
2020
pubmed:
9
2
2020
medline:
19
5
2020
Statut:
epublish
Résumé
Multiple myeloma (MM) is a plasma cell malignancy and most patients eventually succumb to the disease. Chimeric antigen receptor (CAR) T cells targeting B-Cell Maturation Antigen (BCMA) on MM cells have shown high-response rates, but limited durability. CD229/LY9 is a cell surface receptor present on B and T lymphocytes that is universally and strongly expressed on MM plasma cells. Here, we develop CD229 CAR T cells that are highly active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells. We do not observe fratricide during CD229 CAR T cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229
Identifiants
pubmed: 32034142
doi: 10.1038/s41467-020-14619-z
pii: 10.1038/s41467-020-14619-z
pmc: PMC7005855
doi:
Substances chimiques
Antibodies
0
LY9 protein, human
0
Receptors, Antigen, T-Cell
0
Signaling Lymphocytic Activation Molecule Family
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
798Subventions
Organisme : NCI NIH HHS
ID : K24 CA198315
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA042014
Pays : United States
Références
Howlader, N. et al. (eds). SEER Cancer Statistics Review, 1975–2016. Based on November 2018 SEER data submission, posted to the SEER web site, April 2019 (National Cancer Institute, Bethesda, MD, 2019).
Cohen, A. D. et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J. Clin. Invest. 130, 2210–2221 (2019).
doi: 10.1172/JCI126397
Raje, N. et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 380, 1726–1737 (2019).
doi: 10.1056/NEJMoa1817226
Ali, S. A. et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 128, 1688–1700 (2016).
doi: 10.1182/blood-2016-04-711903
Carulli, G. et al. CD229 expression on bone marrow plasma cells from patients with multiple myeloma and monoclonal gammopathies of uncertain significance. Acta Haematol. 135, 11–14 (2016).
doi: 10.1159/000380939
Muccio, V. E. et al. Multiple myeloma: New surface antigens for the characterization of plasma cells in the era of novel agents. Cytom. B Clin. Cytom. 90, 81–90 (2016).
doi: 10.1002/cyto.b.21279
Atanackovic, D. et al. Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma. Haematologica 96, 1512–1520 (2011).
doi: 10.3324/haematol.2010.036814
Yousef, S. et al. CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma. Hum. Vaccin. Immunother. 11, 1606–1611 (2015).
doi: 10.1080/21645515.2015.1046658
Pojero, F. et al. Utility of CD54, CD229, and CD319 for the identification of plasma cells in patients with clonal plasma cell diseases. Cytom. B Clin. Cytom. 90, 91–100 (2016).
doi: 10.1002/cyto.b.21269
Boucher, K. et al. Stemness of B-cell progenitors in multiple myeloma bone marrow. Clin. Cancer Res. 18, 6155–6168 (2012).
doi: 10.1158/1078-0432.CCR-12-0531
Matsui, W. et al. Characterization of clonogenic multiple myeloma cells. Blood 103, 2332–2336 (2004).
doi: 10.1182/blood-2003-09-3064
Pilarski, L. M. & Belch, A. R. Clonotypic myeloma cells able to xenograft myeloma to nonobese diabetic severe combined immunodeficient mice copurify with CD34 (+) hematopoietic progenitors. Clin. Cancer Res. 8, 3198–3204 (2002).
pubmed: 12374689
Garfall, A. L. et al. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N. Engl. J. Med. 373, 1040–1047 (2015).
doi: 10.1056/NEJMoa1504542
Garfall, A. L., et al. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight 3, pii: 120505 (2018).
Gomes-Silva, D. et al. CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood 130, 285–296 (2017).
doi: 10.1182/blood-2017-01-761320
Mamonkin, M., Rouce, R. H., Tashiro, H. & Brenner, M. K. A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood 126, 983–992 (2015).
doi: 10.1182/blood-2015-02-629527
Nicholson, I. C. et al. Construction and characterisation of a functional CD19 specific single chain Fv fragment for immunotherapy of B lineage leukaemia and lymphoma. Mol. Immunol. 34, 1157–1165 (1997).
doi: 10.1016/S0161-5890(97)00144-2
Porter, D. L. et al. A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood 107, 1325–1331 (2006).
doi: 10.1182/blood-2005-08-3373
Gacerez, A. T. & Sentman, C. L. T-bet promotes potent antitumor activity of CD4(+) CAR T cells. Cancer Gene Ther. 25, 117–128 (2018).
doi: 10.1038/s41417-018-0012-7
Haabeth, O. A. et al. Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat. Commun. 2, 240 (2011).
doi: 10.1038/ncomms1239
Kemp, R. A. & Ronchese, F. Tumor-specific Tc1, but not Tc2, cells deliver protective antitumor immunity. J. Immunol. 167, 6497–6502 (2001).
doi: 10.4049/jimmunol.167.11.6497
Gogishvili, T. et al. SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7(+) normal lymphocytes. Blood 130, 2838–2847 (2017).
doi: 10.1182/blood-2017-04-778423
Kumar, S. K. et al. Multiple myeloma. Nat. Rev. Dis. Prim. 3, 17046 (2017).
doi: 10.1038/nrdp.2017.46
Majzner, R. G. & Mackall, C. L. Tumor antigen escape from CAR T-cell therapy. Cancer Discov. 8, 1219–1226 (2018).
doi: 10.1158/2159-8290.CD-18-0442
NCT03710421. CS1-CAR T Therapy Following Chemotherapy in Treating Patients With Relapsed or Refractory CS1 Positive Multiple Myeloma. (ClinicalTrials.gov, 2018).
Malaer, J. D. & Mathew, P. A. CS1 (SLAMF7, CD319) is an effective immunotherapeutic target for multiple myeloma. Am. J. Cancer Res. 7, 1637–1641 (2017).
pubmed: 28861320
pmcid: 5574936
Schofield, D. J. et al. Application of phage display to high throughput antibody generation and characterization. Genome Biol. 8, R254 (2007).
doi: 10.1186/gb-2007-8-11-r254
Vieira, J. & Messing, J. Production of single-stranded plasmid DNA. Methods Enzymol. 153, 3–11 (1987).
doi: 10.1016/0076-6879(87)53044-0
Martin, C. D. et al. A simple vector system to improve performance and utilisation of recombinant antibodies. BMC Biotechnol. 6, 46 (2006).
doi: 10.1186/1472-6750-6-46
Tucker, D. F. et al. Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles. Proc. Natl Acad. Sci. USA 115, E4990–E4999 (2018).
doi: 10.1073/pnas.1716788115
Brogdon, J. et al. Treatment of Cancer Using Humanized Anti-bcma Chimeric Antigen Receptor. (Google Patents, 2016).
Matsui, W. et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 68, 190–197 (2008).
doi: 10.1158/0008-5472.CAN-07-3096
de la Fuente, M. A. et al. Molecular characterization and expression of a novel human leukocyte cell-surface marker homologous to mouse Ly-9. Blood 97, 3513–3520 (2001).
doi: 10.1182/blood.V97.11.3513