Targeted therapy of cancer with radiolabeled antibodies.

TLDR

The review discusses fundamental issues in selecting antibodies, radionuclides, and understanding tumor and host physiology for radioimmunotherapy. The authors examine the application of radiolabeled antibodies, or radioimmunotherapy (RAIT), in cancer treatment. RAIT involves various radioantibody constructs evaluated in clinical studies across hematologic and solid tumors, with therapeutic response influenced by dose rate, tumor size, radiosensitivity, and target‑to‑nontarget ratios, while pretargeting strategies using bispecific antibodies aim to improve tumor selectivity and reduce marrow toxicity. RAIT is increasingly used for hematologic cancers such as non‑Hodgkin lymphoma, with several agents in trials and one recently FDA‑approved, though progress in solid tumors remains limited.

Abstract

This review focuses on the use of radiolabeled antibodies in the therapy of cancer, termed radioimmunotherapy (RAIT). Basic problems concerning the choice of antibody and radionuclide and the physiology of tumor and host are discussed. Then follows a review of pertinent clinical publications on various radioantibody constructs in the treatment of hematopoietic and solid tumors of diverse histopathologies, grades, and stages, and in different clinical settings. Factors such as dose rate delivered, tumor size, and radiosensitivity play a major role in determining therapeutic response, while target-to-nontarget ratios and, particularly, circulating radioactivity to the bone marrow determine the major dose-limiting toxicities. RAIT appears to be gaining a place in the therapy of hematopoietic neoplasms, such as non-Hodgkin's lymphoma, with several agents advancing in clinical trials toward registration, of which one has just been approved by the FDA. Although RAIT of solid tumors has shown less progress, pretargeting strategies, such as an affinity-enhancement system consisting of bispecific antibodies separating targeting from delivery of the radiotherapeutic, appear to enhance tumor-to-nontumor ratios and may increase rad doses to tumor more selectively than directly labeled antibodies.