Genetic engineering of T cells for adoptive immunotherapy.
To be effective for the treatment of cancer and infectious diseases, T cell adoptive immunotherapy requires large numbers of cells with abundant proliferative reserves and intact effector functions. We are achieving these goals using a gene therapy strategy wherein the desired characteristics are introduced into a starting cell population, primarily by high efficiency lentiviral vector-mediated transduction. Modified cells are then expanded using ex vivo expansion protocols designed to minimally alter the desired cellular phenotype. In this article, we focus on strategies to (1) dissect the signals controlling T cell proliferation; (2) render CD4 T cells resistant to HIV-1 infection; and (3) redirect CD8 T cell antigen specificity.
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, 421 Curie Blvd-556 BRB II/III, Philadelphia, PA, 19104, USA.
Angel
A
Varela-Rohena
Carmine
C
Carpenito
Elena E
EE
Perez
Max
M
Richardson
Richard V
RV
Parry
Michael
M
Milone
John
J
Scholler
Xueli
X
Hao
Angela
A
Mexas
Richard G
RG
Carroll
Carl H
CH
June
James L
JL
Riley
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D049109:Cell Proliferation; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*
D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins