Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells.
Adoptive immunotherapy holds promise as a treatment for cancer and infectious diseases, but its development has been impeded by the lack of reproducible methods for generating therapeutic numbers of antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs). As a result, there are only limited reports of expansion of antigen-specific CTLs to the levels required for clinical therapy. To address this issue, artificial antigen-presenting cells (aAPCs) were made by coupling a soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) and CD28-specific antibody to beads. HLA-Ig-based aAPCs were used to induce and expand CTLs specific for cytomegalovirus (CMV) or melanoma. aAPC-induced cultures showed robust antigen-specific CTL expansion over successive rounds of stimulation, resulting in the generation of clinically relevant antigen-specific CTLs that recognized endogenous antigen-major histocompatibility complex complexes presented on melanoma cells. These studies show the value of HLA-Ig-based aAPCs for reproducible expansion of disease-specific CTLs for clinical approaches to adoptive immunotherapy.
Oelke
Mathias
M
Department of Pathology & Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. bmpe5@cs.com
Maus
Marcela V
MV
Didiano
Dominic
D
June
Carl H
CH
Mackensen
Andreas
A
Schneck
Jonathan P
JP
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000951:Antigens, Neoplasm; D003587:Cytomegalovirus / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D007136:Immunoglobulins; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins