Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case.
Although considerable efforts have been made in the discovery of new agents for cancer treatment, several promising therapeutics cannot be applied systemically because of their severe side effects. This is the case for various recombinant pro-inflammatory cytokines that, despite their potent anti-cancer activity, can not find their way to clinical exploitation due to their devastating toxicity shown during dose escalation to therapeutically active concentrations. To circumvent these problems, an elegant and efficient way to accumulate therapeutic agents at the tumor site, thus reducing systemic side effects, is their conjugation to tumor-specific antibodies. Here, we review preclinical data about immunocytokines conjugated to a promising single-chain human antibody that selectively targets tumor-associated stroma and blood vessels by binding with high affinity and specificity to the extra domain-B (EDB) of fibronectin.
Ronca
Roberto
R
Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.
Sozzani
Silvano
S
Presta
Marco
M
Alessi
Patrizia
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005353:Fibronectins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008222:Lymphokines / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012795:Sialoglycoproteins / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; D005353:Fibronectins; C089422:Fv protein, human; D008222:Lymphokines; D012795:Sialoglycoproteins