Whither Radioimmunotherapy: To Be or Not To Be?

Abstract

Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, ¹³¹iodine-tositumomab and ⁹⁰yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities. The dramatically improved therapeutic index of bispecific antibody pretargeting appears to be sufficiently compelling to justify human clinical trials and reinvigorate enthusiasm for radioimmunotherapy in the treatment of malignancies, particularly lymphomas. Cancer Res; 77(9); 2191-6. ©2017 AACR.

Figure 1. Bispecific Antibody Pretargeted Radioimmunotherapy

A bispecific antibody construct was engineered that spontaneously dimerizes after expression by CHO-DG44 cells. One single chain antibody fragment binds with high affinity to the CD20 antigen on B cell malignancies, whereas the other single chain antibody fragment binds with exceptionally high affinity to an ⁹⁰Yttrium-DOTA hapten.