Fusogenics: a recombinant immunotoxin-based screening platform to select internalizing tumor-specific antibody fragments.
Antibody-based therapeutics play a vital role in the treatment of certain cancers; however, despite commercial success, various strategies are being pursued to increase their potency and hence improve patient outcomes. The use of antibodies to deliver a cytotoxic payload offers a promising alternative for more efficacious therapies. Immunotoxins are composed of an internalizing antibody fragment linked to a bacterial or plant toxin. Once internalized, the payload, such as Pseudomonas exotoxin A (PE), blocks protein synthesis and induces apoptosis. Typically, immunotoxins are developed by first isolating a tumor-specific antibody, which is then either chemically linked to a toxin or reengineered as a fusion protein. Here, the authors describe the development of Fusogenics, an immunotoxin-based screening method that selects internalizing tumor-specific antibodies using a functional assay. Selected immune library clones were characterized and shown to be selective against normal tissues and specific to tumor tissues. In summary, the Fusogenics immunotoxin platform represents a unique, single-step selection approach combining specificity and functionality to isolate novel internalizing tumor-specific antibody fragments with potential for direct clinical application in the treatment of cancer.
Viventia Biotechnologies, Inc., Winnipeg, Canada.
Jeannick
J
Cizeau
Marianne G P
MG
Torres
Sharla G
SG
Cowling
Stacy
S
Stibbard
Arjune
A
Premsukh
Joycelyn
J
Entwistle
Glen C
GC
MacDonald
D036002:ADP Ribose Transferases / Q000235:genetics / Q000302:isolation & purification; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D017209:Apoptosis; D001427:Bacterial Toxins / Q000235:genetics / Q000302:isolation & purification; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004926:Escherichia coli; D005098:Exotoxins / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D057166:High-Throughput Screening Assays; D006801:Humans; D007128:Immunoglobulin Fragments / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D000922:Immunotoxins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D037521:Virulence Factors / Q000235:genetics / Q000302:isolation & purification; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000912:Antibodies, Neoplasm; D001427:Bacterial Toxins; D005098:Exotoxins; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A