Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Catherine M BollardCliona M Rooney

Abstract

Tumor cells from approximately 40% of patients with Hodgkin or non-Hodgkin lymphoma express the type II latency Epstein-Barr virus (EBV) antigens latent membrane protein 1 (LMP1) and LMP2, which represent attractive targets for immunotherapy. Because T cells specific for these antigens are present with low frequency and may be rendered anergic by the tumors that express them, we expanded LMP-cytotoxic T lymphocytes (CTLs) from patients with lymphoma using autologous dendritic cells and EBV-transformed B-lymphoblastoid cell lines transduced with an adenoviral vector expressing either LMP2 alone (n = 17) or both LMP2 and ΔLMP1 (n = 33). These genetically modified antigen-presenting cells expanded CTLs that were enriched for specificity against type II latency LMP antigens. When infused into 50 patients with EBV-associated lymphoma, the expanded CTLs did not produce infusional toxicities. Twenty-eight of 29 high-risk or multiple-relapse patients receiving LMP-CTLs as adjuvant therapy remained in remission at a median of 3.1 years after CTL infusion. None subsequently died as a result of lymphoma, but nine succumbed to complications associated with extensive prior chemoradiotherapy, including myocardial infarction and secondary mal...Continue Reading

References

Jan 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·G Miller, M Lipman
Sep 8, 1994·The New England Journal of Medicine·H E HeslopC M Rooney
Feb 2, 1999·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C M RooneyH Heslop
Apr 12, 2002·International Journal of Cancer. Journal International Du Cancer·Pauline MeijJaap M Middeldorp
Jun 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mary L DisisKathy Schiffman
Dec 4, 2002·Nature Reviews. Immunology·Antonio Lanzavecchia, Federica Sallusto
Mar 23, 2004·Annual Review of Immunology·Federica SallustoAntonio Lanzavecchia
Oct 29, 2004·Nature Reviews. Cancer·Lawrence S Young, Alan B Rickinson
Dec 22, 2004·The Journal of Experimental Medicine·Catherine M BollardHelen E Heslop
Sep 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karin C StraathofCatherine M Bollard
Sep 10, 2005·Nature Biotechnology·Janice M ReichertMatthew C Dewitz
Apr 20, 2006·Nature Reviews. Immunology·Luca GattinoniNicholas P Restifo
Sep 27, 2006·Bioinformatics·Stewart T ChangJennifer J Linderman
Dec 2, 2006·Nature Clinical Practice. Oncology·Pawel MuranskiNicholas P Restifo
Jan 24, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonUNKNOWN International Harmonization Project on Lymphoma
Nov 29, 2007·Journal of Clinical Pathology·K L GroggA Dogan
Dec 7, 2007·The Journal of Clinical Investigation·Carolina BergerStanley R Riddell
Jun 27, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B D Cheson
Jun 21, 2008·The New England Journal of Medicine·Naomi N HunderCassian Yee
Feb 25, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Richard A MorganSteven A Rosenberg
Nov 5, 2010·The New England Journal of Medicine·Anas YounesAndres Forero-Torres
May 5, 2011·The Journal of Clinical Investigation·Barbara SavoldoGianpietro Dotti
Sep 13, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Conrad R CruzCatherine M Bollard
Oct 2, 2012·The Journal of Clinical Investigation·Ralf KüppersMartin-Leo Hansmann
Nov 22, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Vanya IchevaTobias Feuchtinger
Mar 27, 2013·The New England Journal of Medicine·Stephan A GruppCarl H June

❮ Previous
Next ❯

Citations

Jun 3, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Richard A Morgan
Jun 6, 2014·Nature Medicine·David Holmes
Jul 17, 2014·Human Gene Therapy·Malcolm K Brenner
Oct 15, 2014·Nature Reviews. Clinical Oncology·Steven A Rosenberg
Dec 2, 2014·Pediatric Clinics of North America·Carl E AllenCatherine M Bollard
Oct 29, 2014·Nature Reviews. Clinical Oncology·Crystal L MackallTerry J Fry
Apr 16, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ann M LeenJuan F Vera
Dec 3, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Frederick R AppelbaumMary M Horowitz
Mar 19, 2014·Cytotherapy·Martin HildebrandtHelen E Heslop
Sep 4, 2015·Annual Review of Medicine·Carlos A RamosMalcolm K Brenner
Jan 7, 2016·Nature Medicine·Christopher A KlebanoffNicholas P Restifo
Nov 4, 2015·Nature Reviews. Clinical Oncology·Connie Lee BatleviAnas Younes
Dec 8, 2015·Immunotherapy·Takumi KumaiYasuaki Harabuchi
Oct 10, 2015·Current Hematologic Malignancy Reports·A A GruP Porcu
Feb 4, 2016·Expert Review of Anticancer Therapy·Ana Battle-LopezMiguel A Piris
Feb 1, 2015·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Jennifer Cuellar-RodriguezDennis D Hickstein
May 20, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M R LuskinR Reshef
Aug 19, 2015·Cancer Letters·Maria Raffaella PetraraAnita De Rossi
Jul 15, 2015·Human Molecular Genetics·Teresa ManzoCliona M Rooney
Apr 12, 2016·British Journal of Haematology·Matthew J BarthMitchell S Cairo
Apr 9, 2015·British Journal of Haematology·John T Sandlund, Sherrie L Perkins
Mar 31, 2015·Blood·David M WeinstockLouis M Staudt
Jul 30, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Arjan C LankesterUNKNOWN Westhafen Intercontinental Group
Jan 16, 2015·The Journal of Infectious Diseases·Julia A SungDavid M Margolis
May 29, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Seok-Goo ChoTai-Gyu Kim
Feb 11, 2015·Clinical Lymphoma, Myeloma & Leukemia·Ranjit Kumar ChaudharyJulie M Vose
May 20, 2015·Biomarkers in Medicine·Joseph G TaylorJohn G Gribben
Jul 23, 2014·Oncoimmunology·Fernando ArandaLorenzo Galluzzi
Apr 21, 2016·American Journal of Hematology·Jorge J CastilloEduardo M Sotomayor
Feb 24, 2015·Annual Review of Immunology·Graham S TaylorAndrew D Hislop
Jan 30, 2015·Frontiers in Oncology·Geir Åge LøsetInger Sandlie
Nov 5, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sharon LamCatherine Bollard
Feb 20, 2015·Hematology·Catherine M Bollard, A John Barrett
May 3, 2016·British Journal of Haematology·Mitchell S Cairo, Ross Pinkerton
May 23, 2016·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Giuseppina Li PiraMauro Montanari
Jun 1, 2016·Leukemia & Lymphoma·Paul J BröckelmannAndreas Engert

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.