Anticancer Antibodies

Abstract

The recent clinical and commercial success of anticancer antibodies such as rituximab and trastuzumab has created great interest in antibody-based therapeutics for hematopoietic malignant neoplasms and solid tumors. Given the likelihood of lower toxic effects of antibodies that target tumor cells and have limited impact on nonmalignant bystander organs vs small molecules, the potential increased efficacy by conjugation to radioisotopes and other cellular toxins, and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, current and future antibody therapeutics are likely to find substantial roles alone and in combination therapeutic strategies for treating patients with cancer. It also is likely that conjugation strategies will add new radiolabeled and toxin-linked products to the market to complement the recent approvals of ibritumomab tiuxetan and gemtuzumab ozogamicin. This review considers the structure of anticancer therapeutic antibodies and the techniques used to reduce their antigenicity. Efficacy and toxic effects, conjugation with isotopes and toxins, and validation of the antibody targets also are discussed. Antibodies approved by the Food and Drug Administration are described in detail, as are antibodies in late and early stages of clinical development.

Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells

“…1,2 In the present work, we sought to further investigate the mechanism of action of the aIGF-1R MoAb A12. Using an IGF-1/insulin-dependent hematopoietic cell line model, FD/IGF-1R, it was found that culture of the cells in IGF-1 along with the aIGF-1R A12 antibody resulted Figure 3 Flow-cytometric analysis of caspase activation following aIGF-1R A12 monoclonal antibody (MoAb) treatment.…”

“…1,2 The promise of these therapies lies with the potential for a high degree of specificity in targeting malignant cells through specific antigenic determinants. Antibodies alone have limited cytotoxic effects on tumor cells, so successful use of this approach requires combination treatment with conventional chemotherapies (e.g.…”

Characterization and Immunotherapeutic Implications for a Novel Antibody Targeting Interleukin (IL)-13 Receptor α2

“…Modifications of those small antibody fragments are often required to enhance their affinity and avidity to targeted proteins. In recent years, monoclonal antibodies have shown increasing success as targeted anticancer and diagnostic agents (25,26), and a further search for high affinity reagents with restricted specificity to tumor-associated antigens is in progress. Historically, the hybridoma cell line specific to the antigen IL13R␣2, however, has been unavailable to the scientific community.…”

PEGylation and Multimerization of the Anti-p185HER-2 Single Chain Fv Fragment 4D5

“…This results in rather low concentrations of scFv molecules in the circulation, which in turn reduces unspecific accumulation in non-target tissues, but it also reduces the total dose localizing to the tumor (19). On the other hand, large molecules, such as whole IgGs, show poor extravasation and slower tissue diffusion (20,21). At the same time, they can exhibit prolonged serum half-lives of up to several weeks (19), because they avoid renal excretion and are instead removed by the more delayed hepatic clearance (22).…”