In vivo functional efficacy of tumor-specific T cells expanded using HLA-Ig based artificial antigen presenting cells (aAPC).
Adoptive immunotherapy for treatment of cancers and infectious diseases is often hampered by a high degree of variability in the final T cell product and in the limited in vivo function and survival of ex vivo expanded antigen-specific cytotoxic T cells (CTL). This has stimulated interest in development of standardized artificial antigen presenting cells (aAPC) to reliably expand antigen specific CTL. However, for successful immunotherapy the aAPC ex vivo generated CTL must have anti-tumor activity in vivo. Here, we demonstrate that HLA-Ig based aAPC stimulated tumor-specific CTL from human peripheral blood T lymphocytes showed robust expansion and functional activity in a human/SCID mouse melanoma model. HLA-Ig based aAPC expanded CTL were detected in the peripheral blood up to 15 days after transfer. Non-invasive bioluminescence imaging of tumor bearing mice demonstrated antigen dependent localization of transferred CTL to the tumor site. Moreover, adoptive transfer of HLA-Ig based aAPC generated CTL inhibited the tumor growth both in prevention and treatment modes of therapy and was comparable to that achieved by dendritic cell expanded CTL. Thus, our data demonstrate potential therapeutic in vivo activity of HLA-Ig based aAPC expanded CTL to control tumor growth.
Department of Pathology, Johns Hopkins School of Medicine, Ross 664G, 720 Rutland Avenue, Baltimore, MD 21205, USA. mdurai1@jhmi.edu
Malarvizhi
M
Durai
Christine
C
Krueger
Zhaohui
Z
Ye
Linzhao
L
Cheng
Andreas
A
Mackensen
Mathias
M
Oelke
Jonathan P
JP
Schneck
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000637:transplantation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D058965:MART-1 Antigen; D008545:Melanoma / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D010455:Peptides