Concepts in radioimmunotherapy and immunotherapy: Radioimmunotherapy from a Lym-1 perspective

Conventional chemotherapy regimens cure fewer than 50% of patients with aggressive non-Hodgkin's lymphoma, and fewer than 5% of patients with indolent lymphomas. However, the majority of patients remain responsive to remarkably low doses of external beam radiotherapy. A logical strategy for the treatment of non-Hodgkin's lymphoma is radioimmunotherapy (RIT); systemic radiation targeted to tumor cells using monoclonal antibodies. RIT involves continuous exposure to low-dose-rate radiation, with the intensity of the dose decreasing over time, and as such is distinct from conventional radiotherapy and chemotherapy. RIT has several advantages over monoclonal antibody therapy. For example, a functional immune system is not an absolute requirement to kill tumor cells, and, depending on the radiolabel used, beta-emissions are effective over 100 to 500 cell diameters, resulting in a crossfire effect on nearby tumor cells. The crossfire effect enables the eradication of cells that are not necessarily targeted by the antibody, but are affected by the radiation. The success of RIT depends on which antibody and radioisotope is used. This article examines how the antibody, radioisotope, chelator, and linker affect the safety and efficacy of RIT. The different approaches to dosing are also considered.