Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes

Swati Naik, Sarah K Nicholas, Caridad A Martinez, Ann M Leen, Patrick J Hanley, Steven M Gottschalk, Cliona M Rooney, I Celine Hanson, Robert A Krance, Elizabeth J Shpall, Conrad R Cruz, Persis Amrolia, Giovanna Lucchini, Nancy Bunin, Jennifer Heimall, Orly R Klein, Andrew R Gennery, Mary A Slatter, Mark A Vickers, Jordan S Orange & 3 others Helen E Heslop, Catherine M Bollard, Michael D Keller

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.

OBJECTIVE: We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.

METHODS: Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.

RESULTS: Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive.

CONCLUSION: VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.

Original languageEnglish
Pages (from-to)1498-1505
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number5
Early online date24 Feb 2016
DOIs
Publication statusPublished - May 2016

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Adoptive Immunotherapy
Viruses
T-Lymphocytes
Virus Diseases
Hematopoietic Stem Cell Transplantation
Human Herpesvirus 4
Therapeutics
X-Linked Combined Immunodeficiency Diseases
Tissue Donors
BK Virus
Human Herpesvirus 6
Cytomegalovirus Infections
Graft vs Host Disease
Immunosuppressive Agents
Adenoviridae
Antiviral Agents
Stem Cells
Transplantation

Keywords

  • primary immunodeficiency
  • immunotherapy
  • cytotoxic T lymphocytes
  • antiviral therapy

Cite this

Naik, S., Nicholas, S. K., Martinez, C. A., Leen, A. M., Hanley, P. J., Gottschalk, S. M., ... Keller, M. D. (2016). Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. Journal of Allergy and Clinical Immunology, 137(5), 1498-1505. https://doi.org/10.1016/j.jaci.2015.12.1311

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. / Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A; Leen, Ann M; Hanley, Patrick J; Gottschalk, Steven M; Rooney, Cliona M; Hanson, I Celine; Krance, Robert A; Shpall, Elizabeth J; Cruz, Conrad R; Amrolia, Persis; Lucchini, Giovanna; Bunin, Nancy; Heimall, Jennifer; Klein, Orly R; Gennery, Andrew R; Slatter, Mary A; Vickers, Mark A; Orange, Jordan S; Heslop, Helen E; Bollard, Catherine M; Keller, Michael D.

In: Journal of Allergy and Clinical Immunology, Vol. 137, No. 5, 05.2016, p. 1498-1505.

Research output: Contribution to journalArticle

Naik, S, Nicholas, SK, Martinez, CA, Leen, AM, Hanley, PJ, Gottschalk, SM, Rooney, CM, Hanson, IC, Krance, RA, Shpall, EJ, Cruz, CR, Amrolia, P, Lucchini, G, Bunin, N, Heimall, J, Klein, OR, Gennery, AR, Slatter, MA, Vickers, MA, Orange, JS, Heslop, HE, Bollard, CM & Keller, MD 2016, 'Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes', Journal of Allergy and Clinical Immunology, vol. 137, no. 5, pp. 1498-1505. https://doi.org/10.1016/j.jaci.2015.12.1311
Naik, Swati ; Nicholas, Sarah K ; Martinez, Caridad A ; Leen, Ann M ; Hanley, Patrick J ; Gottschalk, Steven M ; Rooney, Cliona M ; Hanson, I Celine ; Krance, Robert A ; Shpall, Elizabeth J ; Cruz, Conrad R ; Amrolia, Persis ; Lucchini, Giovanna ; Bunin, Nancy ; Heimall, Jennifer ; Klein, Orly R ; Gennery, Andrew R ; Slatter, Mary A ; Vickers, Mark A ; Orange, Jordan S ; Heslop, Helen E ; Bollard, Catherine M ; Keller, Michael D. / Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. In: Journal of Allergy and Clinical Immunology. 2016 ; Vol. 137, No. 5. pp. 1498-1505.
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abstract = "BACKGROUND: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.OBJECTIVE: We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.METHODS: Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.RESULTS: Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72{\%}) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81{\%} of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80{\%}. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive.CONCLUSION: VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.",
keywords = "primary immunodeficiency, immunotherapy, cytotoxic T lymphocytes, antiviral therapy",
author = "Swati Naik and Nicholas, {Sarah K} and Martinez, {Caridad A} and Leen, {Ann M} and Hanley, {Patrick J} and Gottschalk, {Steven M} and Rooney, {Cliona M} and Hanson, {I Celine} and Krance, {Robert A} and Shpall, {Elizabeth J} and Cruz, {Conrad R} and Persis Amrolia and Giovanna Lucchini and Nancy Bunin and Jennifer Heimall and Klein, {Orly R} and Gennery, {Andrew R} and Slatter, {Mary A} and Vickers, {Mark A} and Orange, {Jordan S} and Heslop, {Helen E} and Bollard, {Catherine M} and Keller, {Michael D}",
note = "Acknowledgements We thank our patients and families; referring colleagues; Dr Malcolm Brenner (Baylor College of Medicine); Dr David Jacobsohn; Dr Brett Loechelt; Dr Cecilia Barese; Fahmida Hoq; Neha Joshi (Children's National Medical Center); the National Heart, Lung, and Blood Institute; the National Cancer Institute (PO1 CA148600); the Leukemia and Lymphoma Society; the Production Assistance for Cellular Therapies (PACT) program; the Clinical Research Center at Texas Children's Hospital; the Dan L. Duncan Institute for Clinical and Translational Research at Baylor College of Medicine; the Clinical Immunology Society; the American Academy of Allergy, Asthma & Immunology ARTrust; the American College of Allergy, Asthma & Immunology; the Amy Strelzer Manasevit Scholar Award; the Clinical and Translational Science Institute at Children's National Medical Center; the Clinical Immunology Society; the staff of the Center for Cell and Gene Therapy at Baylor College of Medicine; the staff of the Division of Blood and Marrow Transplantation and the Program for Cell Enhancement and Technologies for Immunotherapy at Children's National Medical Center; and the Jeffrey Modell Foundation for their support of this research.",
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T1 - Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes

AU - Naik, Swati

AU - Nicholas, Sarah K

AU - Martinez, Caridad A

AU - Leen, Ann M

AU - Hanley, Patrick J

AU - Gottschalk, Steven M

AU - Rooney, Cliona M

AU - Hanson, I Celine

AU - Krance, Robert A

AU - Shpall, Elizabeth J

AU - Cruz, Conrad R

AU - Amrolia, Persis

AU - Lucchini, Giovanna

AU - Bunin, Nancy

AU - Heimall, Jennifer

AU - Klein, Orly R

AU - Gennery, Andrew R

AU - Slatter, Mary A

AU - Vickers, Mark A

AU - Orange, Jordan S

AU - Heslop, Helen E

AU - Bollard, Catherine M

AU - Keller, Michael D

N1 - Acknowledgements We thank our patients and families; referring colleagues; Dr Malcolm Brenner (Baylor College of Medicine); Dr David Jacobsohn; Dr Brett Loechelt; Dr Cecilia Barese; Fahmida Hoq; Neha Joshi (Children's National Medical Center); the National Heart, Lung, and Blood Institute; the National Cancer Institute (PO1 CA148600); the Leukemia and Lymphoma Society; the Production Assistance for Cellular Therapies (PACT) program; the Clinical Research Center at Texas Children's Hospital; the Dan L. Duncan Institute for Clinical and Translational Research at Baylor College of Medicine; the Clinical Immunology Society; the American Academy of Allergy, Asthma & Immunology ARTrust; the American College of Allergy, Asthma & Immunology; the Amy Strelzer Manasevit Scholar Award; the Clinical and Translational Science Institute at Children's National Medical Center; the Clinical Immunology Society; the staff of the Center for Cell and Gene Therapy at Baylor College of Medicine; the staff of the Division of Blood and Marrow Transplantation and the Program for Cell Enhancement and Technologies for Immunotherapy at Children's National Medical Center; and the Jeffrey Modell Foundation for their support of this research.

PY - 2016/5

Y1 - 2016/5

N2 - BACKGROUND: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.OBJECTIVE: We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.METHODS: Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.RESULTS: Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive.CONCLUSION: VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.

AB - BACKGROUND: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.OBJECTIVE: We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.METHODS: Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.RESULTS: Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive.CONCLUSION: VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.

KW - primary immunodeficiency

KW - immunotherapy

KW - cytotoxic T lymphocytes

KW - antiviral therapy

U2 - 10.1016/j.jaci.2015.12.1311

DO - 10.1016/j.jaci.2015.12.1311

M3 - Article

VL - 137

SP - 1498

EP - 1505

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 5

ER -