Immuno-gene therapy of established prostate tumors using chimeric receptor-redirected human lymphocytes.
Targeted adoptive immunotherapy is an attractive option for prostate cancer given its accessible primary location, the presence of specific tissue and tumor antigens, and the acceptability of collateral destruction of healthy prostrate tissue. The "T-body" approach, which uses genetically programmed, patient-derived lymphocytes transfected with chimeric receptor genes, combines the effector functions of T lymphocytes and natural killer cells with the ability of antibodies to recognize predefined surface antigens with high specificity and in a non-MHC restricted manner. We evaluated the therapeutic efficacy of anti-erbB2 chimeric receptor-bearing human lymphocytes on human prostate cancer xenografts in a SCID mouse model. Local delivery of erbB2-specific T bodies to well-established s.c. and orthotopic tumors, together with systemic administration of interleukin-2, resulted in retardation of both tumor growth and prostate-specific antigen secretion, prolongation of survival, and complete tumor elimination in a significant number of mice. These preclinical studies demonstrate the therapeutic potential of the T-body approach for locally advanced or recurrent prostate cancer as an adjunct to, or after, conventional therapy.
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Jehonathan H
JH
Pinthus
Tova
T
Waks
Keren
K
Kaufman-Francis
Daniel G
DG
Schindler
Alon
A
Harmelin
Hannah
H
Kanety
Jacob
J
Ramon
Zelig
Z
Eshhar
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D000728:Androgens / Q000502:physiology; D000818:Animals; D002455:Cell Division / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000276:immunology / Q000628:therapy; D017430:Prostate-Specific Antigen / Q000097:blood / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins