Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors

Johannes L. Zakrzewski; David Suh; John C. Markley; Odette M. Smith; Christopher King; Gabrielle L. Goldberg; Robert Jenq; Amanda M. Holland; Jeremy Grubin; Javier Cabrera-Perez; Renier J. Brentjens; Sydney X. Lu; Gabrielle Rizzuto; Derek B. Sant'Angelo; Isabelle Riviere; Michel Sadelain; Glenn Heller; Juan Carlos Zú̃iga-Pflücker; Chen Lu; Marcel R.M. Van Den Brink

doi:10.1038/nbt1395

Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors

Johannes L. Zakrzewski, David Suh, John C. Markley, Odette M. Smith, Christopher King, Gabrielle L. Goldberg, Robert Jenq, Amanda M. Holland, Jeremy Grubin, Javier Cabrera-Perez, Renier J. Brentjens, Sydney X. Lu, Gabrielle Rizzuto, Derek B. Sant'Angelo, Isabelle Riviere, Michel Sadelain, Glenn Heller, Juan Carlos Zú̃iga-Pflücker, Chen Lu, Marcel R.M. Van Den Brink

Research output: Contribution to journal › Article › peer-review

101 Scopus citations

Abstract

We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.

Original language	English (US)
Pages (from-to)	453-461
Number of pages	9
Journal	Nature biotechnology
Volume	26
Issue number	4
DOIs	https://doi.org/10.1038/nbt1395
State	Published - Apr 2008
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

Access to Document

10.1038/nbt1395

Cite this

Zakrzewski, J. L., Suh, D., Markley, J. C., Smith, O. M., King, C., Goldberg, G. L., Jenq, R., Holland, A. M., Grubin, J., Cabrera-Perez, J., Brentjens, R. J., Lu, S. X., Rizzuto, G., Sant'Angelo, D. B., Riviere, I., Sadelain, M., Heller, G., Zú̃iga-Pflücker, J. C., Lu, C., & Van Den Brink, M. R. M. (2008). Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors. Nature biotechnology, 26(4), 453-461. https://doi.org/10.1038/nbt1395

Zakrzewski, JL, Suh, D, Markley, JC, Smith, OM, King, C, Goldberg, GL, Jenq, R, Holland, AM, Grubin, J, Cabrera-Perez, J, Brentjens, RJ, Lu, SX, Rizzuto, G, Sant'Angelo, DB, Riviere, I, Sadelain, M, Heller, G, Zú̃iga-Pflücker, JC, Lu, C & Van Den Brink, MRM 2008, 'Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors', Nature biotechnology, vol. 26, no. 4, pp. 453-461. https://doi.org/10.1038/nbt1395

@article{ed0c128f3e7244b9928526763506b48c,

title = "Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors",

abstract = "We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.",

author = "Zakrzewski, {Johannes L.} and David Suh and Markley, {John C.} and Smith, {Odette M.} and Christopher King and Goldberg, {Gabrielle L.} and Robert Jenq and Holland, {Amanda M.} and Jeremy Grubin and Javier Cabrera-Perez and Brentjens, {Renier J.} and Lu, {Sydney X.} and Gabrielle Rizzuto and Sant'Angelo, {Derek B.} and Isabelle Riviere and Michel Sadelain and Glenn Heller and Z{\'u}̃iga-Pfl{\"u}cker, {Juan Carlos} and Chen Lu and {Van Den Brink}, {Marcel R.M.}",

note = "Funding Information: This work was supported by grants HL69929, CA33049 and CA107096 from the National Institutes of Health (NIH), by awards from the Leukemia and Lymphoma Society, the Ryan Gibson Foundation, the Elsa U. Pardee Foundation, the Byrne Fund, the Emerald Foundation and The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center funded by William H. Goodwin and Alice Goodwin and the Commonwealth Foundation for Cancer Research (M.R.M.v.d.B.). J.L.Z. is the recipient of a fellowship grant from the Lymphoma Research Foundation, J.C.M. and G.R. are supported by a Cancer Research Institute Pre-Doctoral Fellowship and by NIH MSTP grant GM07739, M.S. and J.C.M are supported by NIH grant CA40350, M.S., I.R. and J.C.M. are supported by NIH grant CA59350, and J.C.Z.-P. is supported by a Canada Research Chair in Developmental Immunology. Technical services provided by the MSKCC Small-Animal Imaging Core Facility, supported in part by NIH Small-Animal Imaging Research Program (SAIRP) grant R24 CA83084 and NIH Center grant P30 CA08748, are gratefully acknowledged. The authors would like to thank the staff of the Research Animal Resource Center for excellent animal care. A20, a B-cell lymphoma cell line derived from BALB/c mice, and Renca, a renal cell carcinoma cell line derived from BALB/c mice, were kindly provided by A. Houghton (Memorial Sloan Kettering Cancer Center).",

year = "2008",

month = apr,

doi = "10.1038/nbt1395",

language = "English (US)",

volume = "26",

pages = "453--461",

journal = "Nature biotechnology",

issn = "1087-0156",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors

AU - Zakrzewski, Johannes L.

AU - Suh, David

AU - Markley, John C.

AU - Smith, Odette M.

AU - King, Christopher

AU - Goldberg, Gabrielle L.

AU - Jenq, Robert

AU - Holland, Amanda M.

AU - Grubin, Jeremy

AU - Cabrera-Perez, Javier

AU - Brentjens, Renier J.

AU - Lu, Sydney X.

AU - Rizzuto, Gabrielle

AU - Sant'Angelo, Derek B.

AU - Riviere, Isabelle

AU - Sadelain, Michel

AU - Heller, Glenn

AU - Zú̃iga-Pflücker, Juan Carlos

AU - Lu, Chen

AU - Van Den Brink, Marcel R.M.

N1 - Funding Information: This work was supported by grants HL69929, CA33049 and CA107096 from the National Institutes of Health (NIH), by awards from the Leukemia and Lymphoma Society, the Ryan Gibson Foundation, the Elsa U. Pardee Foundation, the Byrne Fund, the Emerald Foundation and The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center funded by William H. Goodwin and Alice Goodwin and the Commonwealth Foundation for Cancer Research (M.R.M.v.d.B.). J.L.Z. is the recipient of a fellowship grant from the Lymphoma Research Foundation, J.C.M. and G.R. are supported by a Cancer Research Institute Pre-Doctoral Fellowship and by NIH MSTP grant GM07739, M.S. and J.C.M are supported by NIH grant CA40350, M.S., I.R. and J.C.M. are supported by NIH grant CA59350, and J.C.Z.-P. is supported by a Canada Research Chair in Developmental Immunology. Technical services provided by the MSKCC Small-Animal Imaging Core Facility, supported in part by NIH Small-Animal Imaging Research Program (SAIRP) grant R24 CA83084 and NIH Center grant P30 CA08748, are gratefully acknowledged. The authors would like to thank the staff of the Research Animal Resource Center for excellent animal care. A20, a B-cell lymphoma cell line derived from BALB/c mice, and Renca, a renal cell carcinoma cell line derived from BALB/c mice, were kindly provided by A. Houghton (Memorial Sloan Kettering Cancer Center).

PY - 2008/4

Y1 - 2008/4

N2 - We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.

AB - We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.

UR - http://www.scopus.com/inward/record.url?scp=41849106141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41849106141&partnerID=8YFLogxK

U2 - 10.1038/nbt1395

DO - 10.1038/nbt1395

M3 - Article

C2 - 18376399

AN - SCOPUS:41849106141

SN - 1087-0156

VL - 26

SP - 453

EP - 461

JO - Nature biotechnology

JF - Nature biotechnology

IS - 4

ER -

Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this