Catumaxomab

A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19+tumor cells

“…6 The second approach utilizes T cell recruitment via an engineered bispecific antibody, either full-length or fragment, possessing affinity for both a tumor-targeting cellular marker and, commonly, the activating receptor CD3. One such full-length bispecific antibody that recruits T, and natural killer (NK), cells, anti-Epcam/CD3 catumaxomab, 7 is approved for malignant ascites while another, anti-CD20/CD3 FBTA05 8 is in a clinical trial for B cell malignancies. However, the most promising bispecific antibody to date is the bispecific T cell engager (BiTE) blinatumomab, a tandem singlechain variable fragment (scFv) antibody targeting CD19/CD3 that was recently approved for the treatment of the B cell malignancy B-precursor acute lymphoblastic leukemia (B-ALL).…”

A dual-targeting triplebody mediates preferential redirected lysis of antigen double-positive over single-positive leukemic cells

“…First milestones were the creation of hybrid-hybridomas or quadromas and of chemically-coupled Fab-fragments. [9][10][11][12][13] The production of recombinant heterodimeric immunoglobulins through the expression of two different H-and L-chains in the same cell was initially hampered by the "chain association problem." In this case only 12.5% of the resulting total antibody proteins are the desired heterodimers, the rest are unwelcome chain combinations.…”

‘In-Format’ screening of a novel bispecific antibody format reveals significant potency improvements relative to unformatted molecules

“…First generation BsAbs, such as those derived from hybrid hybridomas, quadromas, or by chemical cross-linking of mAbs, have served to demonstrate the promise of the approach, both in preclinical animal models and in the clinic. [4][5] The challenges faced when manufacturing large homogeneous batches of material, and poor clinical efficacy, often due to the emergence of immunogenicity induced by rodent-derived antibodies, as for other biopharmaceuticals with a large proportion of non-human sequence, proved to be major limitations for progression of these types of molecules. 6,7 More recently, alternative genetically-engineered BsAb formats have been described.…”