The use of radioimmunoconjugates in stem cell transplantation

Abstract

Summary:Radiolabeled monoclonal antibodies have been used with encouraging results in conjunction with stem cell transplantation for patients with hematologic malignancies targeting a variety of surface antigens including CD33, CD45 and CD66 for leukemias, CD20 and CD22 for non-Hodgkin's lymphomas, and ferritin for Hodgkin's disease. The results obtained targeting epithelial antigens on solid tumors, however, have generally been less encouraging, primarily due to the relative insensitivity of these malignancies to ionizing radiation. In this report we review clinical studies that have incorporated myeloablative doses of targeted radiation using radiolabeled antibodies in conjunction with stem cell transplant regimens.

188Re or 90Y‐labelled anti‐CD66 antibody as part of a dose‐reduced conditioning regimen for patients with acute leukaemia or myelodysplastic syndrome over the age of 55: results of a phase I–II study

“…Furthermore current experience suggests that RIC transplant regimens are not particularly effective in controlling aggressive malignancies, such as AML, and that dose intensity is a critical factor in this context (Giralt et al, 1997;de Lima et al, 2004). We were interested in evaluating an alternative approach to reducing organ toxicity, namely targeted radiotherapy (Corcoran et al, 1996;Pagel et al, 2002). Both animal studies and phase I-II clinical trials have demonstrated that monoclonal antibodies labelled with a radioactive isotope can be used to deliver high doses of radiation to the bone marrow (BM) and the spleen (Matthews et al, 1992, Matthews et al, 1999Pagel et al, 2002;Burke et al, 2003).…”

“…We were interested in evaluating an alternative approach to reducing organ toxicity, namely targeted radiotherapy (Corcoran et al, 1996;Pagel et al, 2002). Both animal studies and phase I-II clinical trials have demonstrated that monoclonal antibodies labelled with a radioactive isotope can be used to deliver high doses of radiation to the bone marrow (BM) and the spleen (Matthews et al, 1992, Matthews et al, 1999Pagel et al, 2002;Burke et al, 2003). In a previous study, we used an anti-CD66 monoclonal antibody which binds to early normal granulopoietic cells labelled with 188 Re to intensify the conditioning regimen for patients with high-risk leukaemias (Bunjes et al, 2001;Bunjes, 2002).…”

The immune system as a foundation for immunologic therapy and hematologic malignancies: a historical perspective

“…In addition, b-emitting radionuclides conjugated to mAb directed against the CD45 antigen (expressed on all U N C O R R E C T E D P R O O F hematopoietic cells) have been investigated as a way of increasing the anti-leukemic potency of conditioning regimens for HCTwithout inducing undue systemic toxicities. 25,26 The aim of this chapter is to provide a brief historical overview of immunotherapeutic approaches developed to treat hematological malignancies. We have divided the chapter into three sections: (1) immunotherapy with allogeneic HCT; (2) autologous cell-based immunotherapy and vaccines; and (3) antibody-based therapies.…”

“…22 An example of a radiolabeled mAb is a 131 I-anti-CD45 antibody used before allogeneic HCT. 25 The second group of mAbs was directed at target antigens that are internalized after binding, such as CD33. Internalization has been required for those mAbs that were developed for delivering toxins or chemotherapeutic drugs into the cytoplasm of tumor cells.…”

Antibody-targeted radiation cancer therapy

“…The CR rate, remission duration and the ORR from either single or fractionated doses of B-cell malignancies has been more impressive in clinical trials administering high myeloablative doses in conjunction with either autologous bone-marrow transplantation (BMT) or stem-cell transplantation (SCT) 60,[67][68][69][70] . This is significant, as it is often found that therapeutic doses of radioactivity delivered by an mAb cannot be administered without BMT or SCT support.…”