Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

British Journal of Cancer
D J GottliebC Traversari

Abstract

Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I- and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLA-identical siblings. CD4(+) clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-gamma in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferon-gamma after melanoma stimulation. No CD4(+) clones responded to stimulation with recipient haemopoietic cells. The majority of CD8(+) clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4(+) clone was determined to b...Continue Reading

References

Oct 15, 1989·International Journal of Cancer. Journal International Du Cancer·B Van den EyndeT Boon
Mar 15, 1987·International Journal of Cancer. Journal International Du Cancer·M HérinT Boon
Jan 1, 1994·Annual Review of Immunology·T BoonA Van Pel
Aug 1, 1993·Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy·P G CoulieT Boon
Mar 2, 1999·The Journal of Experimental Medicine·P ChauxP van der Bruggen
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R W ChildsJ Barrett
Mar 29, 2000·Bone Marrow Transplantation·J O BayD Blaise
Sep 5, 2002·International Journal of Cancer. Journal International Du Cancer·Toshiro KurokawaAndreas Mackensen
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul F RobbinsSteven A Rosenberg
Mar 6, 2003·Journal of Cancer Research and Clinical Oncology·M HänelF Kroschinsky
Jun 14, 2003·Journal of Immunotherapy·Annette NolteJoachim Kienast
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jianping HuangPaul F Robbins
Jan 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maja MandicHassane M Zarour
Apr 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark E DudleySteven A Rosenberg

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Citations

Dec 18, 2014·Expert Opinion on Biological Therapy·Giulia MesianoDario Sangiolo

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Methods Mentioned

BETA
biopsies
FCS
light microscopy
ELISA

Software Mentioned

CellQuest

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