Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer

Nancy M. Hardy, Miriam E. Mossoba, Seth M. Steinberg, Vicki Fellowes, Xiao Yi Yan, Frances T. Hakim, Rebecca R. Babb, Daniele Avila, Juan Gea-Banacloche, Claude Sportes, Bruce L. Levine, Carl H. June, Hahn M. Khuu, Ashley E. Carpenter, Michael C. Krumlauf, Andrew J. Dwyer, Ronald E. Gress, Daniel H. Fowler, Michael R. Bishop

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose: Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD, whereas type-I-polarized T cells mediate more potent graftversus- tumor (GVT) effects. This phase I translational study evaluated adoptive transfer of ex vivo costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD) allogeneic stem cell transplantation (AlloSCT) for MBC. Experimental Design: Patients had received anthracycline, taxane, and antibody therapies, and been treated for metastatic disease and a human leukocyte antigen (HLA)-identical-sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti-CD28 antibody-coated magnetic beads in interleukin (IL)-2/IL-4-supplemented media. Patients received reduced intensity conditioning, donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, and tumor response; results were compared with historical controls, identically treated except for T1/T2 product infusions. Results: Mixed type-I/type-IICD4 + T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at dose level 1 (5 × 10 6 cells/kg). T-cell donor chimerism reached 100% by a median of 28 days. Seven (78%) developed acute GVHD. At day +28, five patients had partial responses (56%) and none had MBC progression; thereafter, two patients had continued responses. Donor T-cell engraftment and tumor responses appeared faster than in historical controls, but GVHD rates were similar and responders progressed early, often following treatment of acute GVHD. Conclusion: Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses.

Original languageEnglish (US)
Pages (from-to)6878-6887
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number21
DOIs
StatePublished - Nov 1 2011

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Adoptive Transfer
Graft vs Host Disease
Breast Neoplasms
T-Lymphocytes
Tissue Donors
Stem Cell Transplantation
Neoplasms
Lymphocytes
Chimerism
Anthracyclines
HLA Antigens
Interleukin-4
Interleukin-2
Siblings
Anti-Idiotypic Antibodies
Research Design
Stem Cells
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hardy, N. M., Mossoba, M. E., Steinberg, S. M., Fellowes, V., Yan, X. Y., Hakim, F. T., ... Bishop, M. R. (2011). Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. Clinical Cancer Research, 17(21), 6878-6887. https://doi.org/10.1158/1078-0432.CCR-11-1579

Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. / Hardy, Nancy M.; Mossoba, Miriam E.; Steinberg, Seth M.; Fellowes, Vicki; Yan, Xiao Yi; Hakim, Frances T.; Babb, Rebecca R.; Avila, Daniele; Gea-Banacloche, Juan; Sportes, Claude; Levine, Bruce L.; June, Carl H.; Khuu, Hahn M.; Carpenter, Ashley E.; Krumlauf, Michael C.; Dwyer, Andrew J.; Gress, Ronald E.; Fowler, Daniel H.; Bishop, Michael R.

In: Clinical Cancer Research, Vol. 17, No. 21, 01.11.2011, p. 6878-6887.

Research output: Contribution to journalArticle

Hardy, NM, Mossoba, ME, Steinberg, SM, Fellowes, V, Yan, XY, Hakim, FT, Babb, RR, Avila, D, Gea-Banacloche, J, Sportes, C, Levine, BL, June, CH, Khuu, HM, Carpenter, AE, Krumlauf, MC, Dwyer, AJ, Gress, RE, Fowler, DH & Bishop, MR 2011, 'Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer', Clinical Cancer Research, vol. 17, no. 21, pp. 6878-6887. https://doi.org/10.1158/1078-0432.CCR-11-1579
Hardy, Nancy M. ; Mossoba, Miriam E. ; Steinberg, Seth M. ; Fellowes, Vicki ; Yan, Xiao Yi ; Hakim, Frances T. ; Babb, Rebecca R. ; Avila, Daniele ; Gea-Banacloche, Juan ; Sportes, Claude ; Levine, Bruce L. ; June, Carl H. ; Khuu, Hahn M. ; Carpenter, Ashley E. ; Krumlauf, Michael C. ; Dwyer, Andrew J. ; Gress, Ronald E. ; Fowler, Daniel H. ; Bishop, Michael R. / Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 21. pp. 6878-6887.
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abstract = "Purpose: Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD, whereas type-I-polarized T cells mediate more potent graftversus- tumor (GVT) effects. This phase I translational study evaluated adoptive transfer of ex vivo costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD) allogeneic stem cell transplantation (AlloSCT) for MBC. Experimental Design: Patients had received anthracycline, taxane, and antibody therapies, and been treated for metastatic disease and a human leukocyte antigen (HLA)-identical-sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti-CD28 antibody-coated magnetic beads in interleukin (IL)-2/IL-4-supplemented media. Patients received reduced intensity conditioning, donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, and tumor response; results were compared with historical controls, identically treated except for T1/T2 product infusions. Results: Mixed type-I/type-IICD4 + T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at dose level 1 (5 × 10 6 cells/kg). T-cell donor chimerism reached 100{\%} by a median of 28 days. Seven (78{\%}) developed acute GVHD. At day +28, five patients had partial responses (56{\%}) and none had MBC progression; thereafter, two patients had continued responses. Donor T-cell engraftment and tumor responses appeared faster than in historical controls, but GVHD rates were similar and responders progressed early, often following treatment of acute GVHD. Conclusion: Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses.",
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T1 - Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer

AU - Hardy, Nancy M.

AU - Mossoba, Miriam E.

AU - Steinberg, Seth M.

AU - Fellowes, Vicki

AU - Yan, Xiao Yi

AU - Hakim, Frances T.

AU - Babb, Rebecca R.

AU - Avila, Daniele

AU - Gea-Banacloche, Juan

AU - Sportes, Claude

AU - Levine, Bruce L.

AU - June, Carl H.

AU - Khuu, Hahn M.

AU - Carpenter, Ashley E.

AU - Krumlauf, Michael C.

AU - Dwyer, Andrew J.

AU - Gress, Ronald E.

AU - Fowler, Daniel H.

AU - Bishop, Michael R.

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Purpose: Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD, whereas type-I-polarized T cells mediate more potent graftversus- tumor (GVT) effects. This phase I translational study evaluated adoptive transfer of ex vivo costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD) allogeneic stem cell transplantation (AlloSCT) for MBC. Experimental Design: Patients had received anthracycline, taxane, and antibody therapies, and been treated for metastatic disease and a human leukocyte antigen (HLA)-identical-sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti-CD28 antibody-coated magnetic beads in interleukin (IL)-2/IL-4-supplemented media. Patients received reduced intensity conditioning, donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, and tumor response; results were compared with historical controls, identically treated except for T1/T2 product infusions. Results: Mixed type-I/type-IICD4 + T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at dose level 1 (5 × 10 6 cells/kg). T-cell donor chimerism reached 100% by a median of 28 days. Seven (78%) developed acute GVHD. At day +28, five patients had partial responses (56%) and none had MBC progression; thereafter, two patients had continued responses. Donor T-cell engraftment and tumor responses appeared faster than in historical controls, but GVHD rates were similar and responders progressed early, often following treatment of acute GVHD. Conclusion: Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses.

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