MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+ T cells exhibit multifunctional effector and helper responses, in vitro.
MHC class I-restricted human melanoma epitope MART-1(27-35) specific TCR-engineered CD4+CD25- T cells synthesize Th1 type cytokines and exhibit cytolytic effector function upon cognate stimulation. A detailed characterization of such TCR-engineered CD4+CD25- T cells now reveals that they are multifunctional. For example, they undergo multiple rounds of division, synthesize cytokines (IFN-gamma, TNF-alpha, IL-2, and MIP1ss), lyse target cells, and "help" the expansion of the MART-1(27-35) specific CD8+ T cells when stimulated by the MART-1(27-35) peptide pulsed DC. Multiparametric analyses reveal that a single TCR-engineered CD4+ T cell can perform as many as five different functions. Nearly 100% MART-1(27-35) specific TCR expressing CD4+ T cells can be generated through retroviral vector-based transduction and one round of in vitro stimulation by the peptide pulsed DC. MHC class I-restricted tumor epitope specific TCR transduced CD4+ T cells, therefore, could be useful in immunotherapeutic strategies for melanoma or other human malignancies.
Ray
Swagatam
S
Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Chhabra
Arvind
A
Chakraborty
Nitya G
NG
Hegde
Upendra
U
Dorsky
David I
DI
Chodon
Thinle
T
von Euw
Erika
E
Comin-Anduix
Begonya
B
Koya
Richard C
RC
Ribas
Antoni
A
Economou
James S
JS
Rosenberg
Steven A
SA
Mukherji
Bijay
B
D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology*; D005818:Genetic Engineering; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016233:Immunotherapy, Active; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000166:cytology / Q000276:immunology; D014161:Transduction, Genetic
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; C105787:MART-1-Melan-A(27-35) epitope; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell