Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting

Journal article

Rotolo, A., Caputo Galarce, V., Holubova, M., Baxan, N., Dubois, O., Chaudhry, M.S., Xiao, X., Goudevenou, K., Pitcher, D.S., Petevi, K., Kachramanoglou, C., Iles, S., Naresh, K., Maher, J. and Karadimitris, A. (2018). Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. Cancer Cell. 34 (4), pp. 596-610. https://doi.org/10.1016/j.ccell.2018.08.017
AuthorsRotolo, A., Caputo Galarce, V., Holubova, M., Baxan, N., Dubois, O., Chaudhry, M.S., Xiao, X., Goudevenou, K., Pitcher, D.S., Petevi, K., Kachramanoglou, C., Iles, S., Naresh, K., Maher, J. and Karadimitris, A.
Abstract

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.

KeywordsiNKT ; CAR immunotherapy; B cell malignancies
Year2018
JournalCancer Cell
Journal citation34 (4), pp. 596-610
PublisherCell Press
ISSN1535-6108
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ccell.2018.08.017
Publication dates
Print08 Oct 2018
Publication process dates
Accepted30 Aug 2018
Deposited17 Jun 2021
Publisher's version
License
File Access Level
Open
Permalink -

https://openresearch.lsbu.ac.uk/item/8wz50

Download files

Publisher's version
Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.pdf
License: CC BY-NC-ND 4.0
File access level: Open

  • 70
    total views
  • 83
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis
Katsarou, A., Trasanidis, N., Ponnusamy, K., Kostopoulos, I., Alvarez-Benayas, J., Papaleonidopoulou, F., Keren, K., Sabbattini, P.M. R., Feldhahn, N., Papaioannou, M., Hatjiharissi, E., Sudbery, I., Chaidos, A., Caputo, V. and Karadimitris, A. (2023). MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis. Blood Advances. 7 (21), pp. 6395-6410. https://doi.org/10.1182/bloodadvances.2023009772
Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma
Trasanidis, N., Katsarou, A., Ponnusamy, K., Shen, Y.A., Kostopoulos, I.V., Bergonia, B., Keren, K., Reema, P., Xiao, X., Szydlo, R. M., Sabbattini, P., Roberts, I., Auner, H., Naresh, K., Chaidos, A., Wang, T.L., Magnani, L., Caputo, V. and Karadimitris, A. (2022). Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma. Blood. https://doi.org/10.1182/blood.2021014391
Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma
Alvarez-Benayas, J., Trasanidis, N., Katsarou, A., Ponnusamy, K., Chaidos, A., May, P.C., Xiao, X., Bua, M., Atta, M., Roberts, I., Auner, H.W., Hatjiharissi, E., Papaioannou, M., Caputo Galarce, V., Sudbery, I.M. and Karadimitris, A. (2021). Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma. Nature Communications. 12, p. 5450. https://doi.org/10.1038/s41467-021-25704-2
Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia
Iskander, D., Wang,G., Heuston, E.F., Christodoulidou, C., Psaila, B., Ponnusamy, K., Ren, H., Mokhtari, Z., Robinson, M., Chaidos, A., Trivedi, P., Trasanidis, N., Katsarou, A., Szydlo, R., NISC Comparative Sequencing Program, Palii, C.G., Ziadi, Z., Al-Oqaily, Q., Caputo Galarce, V., Roy, A., Harrington, Y., Karnik, L., Naresh, K., Mead,A.J., Thongjuea, S., Brand, M., de la Fuente, J., Bodine, D.M., Roberts,I. and Karadimitris, A. (2021). Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia. Science Translational Medicine. 13 (610). https://doi.org/10.1126/scitranslmed.abf0113
Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs
Saavedra-Garcia, P., Roman-Trufero, M., Al-Sadah, H.A., Blighe, K., Lopez-Jimenez, E., Christoforou, M., Penfold, L., Capece, D., Xiong, X., Miao, Y., Parzych, K., Caputo, V., Siskos, A.P., Encheva, V., Liu, Z., Thiel, D., Kaiser, M.F., Piazza, P., Chaidos, A., Karadimitris, A., Franzoso, G., Snijders, A.P., Keun, H.C., Oyarzun, D.A., Barahona, M. and Auner, H.W. (2021). Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs. PNAS. 118 (17), p. e2018229118. https://doi.org/10.1073/pnas.2018229118
The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma
Ponnusamy, K., Tzioni, M. M., Begum, M., Robinson, M. E., Caputo, V., Katsarou, A., Trasanidis, N., Xiao, X., Kostopoulos, I. V., Iskander, D., Roberts, I., Trivedi, P., Auner, H. W., Naresh, K., Chaidos, A. and Karadimitris, A. (2021). The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma. Haematologica. https://doi.org/10.3324/haematol.2020.274480
Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation
Machuldova, A., Holubova, M., Caputo, V.S., Cedikova, M., Jindra, P., Houdova, L. and Pitule, P. (2021). Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation. Frontiers in Immunology. 12, p. 651751. https://doi.org/10.3389/fimmu.2021.651751
Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro
Caputo Galarce, V., Trasanidis, N., Xiao, X., Robinson, M. E., Katsarou, A., Ponnusamy, K., Prinjha, R. K., Smithers, N., Chaidos, A., Auner, H. W. and Karadimitris, A. (2021). Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro. iScience. 24 (1), pp. 101989-101989. https://doi.org/10.1016/j.isci.2020.101989
Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study
Dekojová T., Houdová, L., Fatka, J., Pitule, P., Ostašov, P., Gmucová, H., Lysák, D., Jindra, P., Holubová, M. and Caputo Galarce, V. (2020). Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study. Journal of Clinical Medicine. 9 (11), p. 3502. https://doi.org/10.3390/jcm9113502
Evolution of Advanced Chronic Lymphoid Leukemia Unveiled by Single-Cell Transcriptomics: A Case Report
Ostasov, P., Robertson, H., Piazza, P., Datta, A., Apperley, J., Houdova, L., Lysak, D., Holubova, M., Tesarova, K., Caputo Galarce, V. and Barrozzi, I. (2020). Evolution of Advanced Chronic Lymphoid Leukemia Unveiled by Single-Cell Transcriptomics: A Case Report. Frontiers in Oncology. 10, p. 2356. https://doi.org/10.3389/fonc.2020.584607
Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells
Holubova, M., Leba, M., Gmucova, H., Caputo Galarce, V., Jindra, P. and Lysak, D. (2019). Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells. International Journal of Molecular Sciences. 20 (14), p. 3472. https://doi.org/10.3390/ijms20143472
The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation
Parzych, K., Saavedra-García, P., Valbuena, G.N., Al-Sadah, H.A., Robinson, M.E., Penfold, L., Kuzeva, D.M., Ruiz-Tellez, A,, Loaiza, S,, Holzmann, V., Caputo Galarce, V., Johnson, D.C., Kaiser, M.F., Karadimitris, A,, Lam, E.W.F, Chevet, E., Feldhahn, N., Keun, H.C. and Auner, H.W. (2019). The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation. Oncogene. 38, p. 3216–3231. https://doi.org/10.1038/s41388-018-0651-z
Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways
Psaila, B., Barkas, N., Iskander, D., Roy, A., Anderson, S., Ashley, N., Caputo Galarce, V., Lichtenberg, J., Loaiza, S., Bodine, D.M., Karadimitris, A., Mead, A.J. and Roberts, I. (2016). Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways. Genome Biology. 17 (1). https://doi.org/10.1186/s13059-016-0939-7