Update: Recombinant Antibodies: From the Laboratory to the Clinic

Abstract

The development of recombinant antibodies has facilitated the exploitation of the Ab-Ag interaction specificity for targeted therapies. A fully human antibody, with custom integrated designs, can be obtained in one-third the time, compared to development of antibodies by hybridoma technology. Recombinant antibodies can be tailored for specific applications, "armed" with cytotoxic agents in a controllable fashion, and used for extracellular and intracellular targeting. Multitargeted and combination therapies are rapidly evolving for the treatment of cancer. Antibody therapeutics, costly to develop and produce, have proven beneficial in the clinic.

In vivo Targeting of Dead Tumor Cells in a Murine Tumor Model Using a Monoclonal Antibody Specific for the La Autoantigen

“…However, due to its rapid blood clearance, maximum tumor accumulation of 111 In-labeled 3B9 (Fab) 2 in treated mice was significantly reduced compared with peak accumulation of 111 In-labeled 3B9 IgG. Therefore, our results are typical of other studies in which the extended blood pool activity of whole IgG enhances tumor uptake but reduces tumor/background ratios, whereas the reduced blood pool activity of (Fab) 2 reduces tumor uptake but enhances tumor/background ratios (45,46). Hence, scheduling of the 3B9 injection after chemotherapy and use of F(ab) 2 or Fab fragments or Fc-modified versions of whole IgG (42) may improve tumor/background ratios.…”

Antibody–cytokine fusion proteins: applications in cancer therapy

“…L19-(GM-CSF) was constructed in the diabody format (two non-covalently associated scFvs) by fusing mGM-CSF to the carboxy-terminus of each scFv, which improves the pharmacokinetic properties and the avidity of the antibody-cytokine fusion protein due to its bivalent nature [25,27,145]. This antibody-(mGM-CSF) fusion protein has good tumor organ distribution and dramatically reduced the tumor growth in 129SvEv mice injected subcutaneously with F9 murine teratocarcinoma or C51 murine colon adenocarcinoma cells.…”

“…The V L -V H (scFv) are joined using a peptide linker, such as (Gly 4 -Ser) 3 [23,24] to stabilize the proper binding structure in these molecules ( Figure 1C). Minibodies are alternative antibody fragments that consist of two scFv regions, a hinge region and the C H 3 domain ( Figure 1C) [25,26]. These smaller antibody fragments have faster clearance from the body and better tissue/tumor penetration.…”

“…These smaller antibody fragments have faster clearance from the body and better tissue/tumor penetration. Intact antibodies, such human IgG1, have a half-life of 3 -4 weeks, while the scFv has a blood clearance of less than 10 h and kidney excretion in 2 -4 h [4,25]. These features make antibody fragments useful in diagnostic applications and tumor imaging [26,27].…”

“…These features make antibody fragments useful in diagnostic applications and tumor imaging [26,27]. The scFvFc format consists of two scFv regions, a hinge region and C H 2-C H 3 domains that allow it to specifically recognize the antigen and also bind Fc gamma receptors (FcγRs) ( Figure 1C) [4,25,26]. The disadvantage of these fragments (with the exception of scFv-Fc fragment) is that although they retain the capacity for antigen binding, they have lost the ability to induce Fc effector functions including ADCC, which is a relevant antitumoral mechanism of therapeutic antibodies [4,28].…”