Generation of functional scFv intrabodies for triggering anti-tumor immunity.
Intracellular expression of recombinant antibodies (intrabodies) allows to interfere with the functions of oncogenic or viral molecules expressed in different cell compartments and has therefore a vast clinical potential in therapy. Although the use of phage-display libraries has made it possible to select Fab or single chain Fv (scFv) antibody fragments usable for intracellular targeting, a major source of recombinant antibodies for therapeutic use still remains hybridoma B cells producing well-characterized monoclonal antibodies (mAbs). However, the cloning and the intracellular expression of antibody fragments derived from mAbs can be markedly hampered by a number of technical difficulties that include failure of cloning functional variable regions as well as lack of binding of the antibody fragments to the targeted molecule in an intracellular environment. We discuss herein various molecular methods that have been developed to generate functional recombinant antibody fragments usable as anti-tumor triggering agents when expressed in tumor cells. Such antibodies can neutralize or modify the activity of oncogenic molecules when addressed in specific subcellular compartments and/or they can be used to trigger anti-tumor immunity when expressed on tumor cell surface.
INSERM Unité 255, Centre de Recherches Biomédicales des Cordeliers, 15 rue de l'Ecole de Médecine, 75270 Paris cedex 06 Paris, France.
Emmanuelle
E
Bonnin
Nadège
N
Gruel
Sandrine
S
Moutel
Adriana R
AR
Mantegazza
Marcela M
MM
Barrio
José
J
Mordoh
Jean-Luc
JL
Teillaud
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular; D007128:Immunoglobulin Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D015202:Protein Engineering / Q000379:methods*; D041701:Swiss 3T3 Cells
D000906:Antibodies; D000970:Antineoplastic Agents; D007128:Immunoglobulin Fragments; C055966:immunoglobulin Fv