Potent antitumour activity of a new class of tumour-specific killer cells.
Two approaches to the antibody-directed targeting of toxic or cytolytic activity and augmentation of cellular immune responses have been explored for tumour immunotherapy, but so far success has been limited. Obstacles facing immunotherapy are the limited accessibility of antibodies or antibody conjugates to solid tumours and the difficulty in obtaining tumour-specific cytotoxic lymphocytes. Here we generate a new class of tumour-specific killer cells by genetically modifying lymphocytes to produce and secrete a targeted toxin against an oncoprotein overexpressed on breast and other tumour cells. The transduced lymphocytes were shown to have potent and selective cytotoxicity to tumours in culture and nude mouse models. The potent in vivo antitumour activity is probably a result of the migration of the lymphocytes to tumours as a targeted toxin carrier, and production and accumulation of the targeted toxins inside tumours as a producer. Our approach, which has features of both antibody-directed and cell-mediated immunotherapy, may have application in a gene therapy context.
Chen
S Y
SY
Department of Cancer Biology, Comprehensive Cancer Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA. sichen@bgsm.edu
Yang
A G
AG
Chen
J D
JD
Kute
T
T
King
C R
CR
Collier
J
J
Cong
Y
Y
Yao
C
C
Huang
X F
XF
D036002:ADP Ribose Transferases; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000235:genetics / Q000627:therapeutic use; D019556:COS Cells; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005098:Exotoxins / Q000235:genetics* / Q000627:therapeutic use; D005240:Feasibility Studies; D015316:Genetic Therapy; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D007167:Immunotherapy; D000922:Immunotoxins / Q000235:genetics* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D014161:Transduction, Genetic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C055966:immunoglobulin Fv