ABSTRACT
Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventional treatment. The purpose of this review is to summarize the current progress of RIT for treating non-Hodgkin's lymphoma (NHL) based on recent preclinical and clinical studies. The efficacy of RIT targeting the B-lymphocyte antigen cluster of differentiation 20 (CD20) has been demonstrated in clinical trials. Two radioimmunoconjugates targeting CD20, yttrium-90 (90Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (131I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Although these two radioimmunoconjugates are effective and least toxic, they have not achieved popularity due to increasing access to novel therapies and the complexity of their delivery process. RIT is constantly evolving with the identification of novel targets and novel therapeutic strategies using newer radionuclides such as alpha-particle isotopes. Alpha-particles show very short path lengths and high linear energy transfer. These characteristics provide increased tumor cell-killing activities and reduced non-specific bystander responses on normal tissue. This review also discusses reviewed pre-targeted RIT (PRIT) and immuno-positron emission tomography (PET). PRIT potentially increases the dose of radionuclide delivered to tumors while toxicities to normal tissues are limited. Immuno-PET is a molecular imaging tracer that combines the high sensitivity of PET with the specific targeting capability of mAb. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response.
ABSTRACT
Primary effusion lymphoma (PEL) is a unique and recently identified non-Hodgkin's lymphoma in immunocompromised individuals. PEL is caused by the Kaposi sarcoma-associated herpes virus/human herpes virus 8 (KSHV/HHV-8) and has a peculiar presentation involving liquid growth in the serous body cavity, chemotherapy resistance and poor prognosis. In search of a new therapeutic modality for PEL, we examined the effect of γ-irradiation on PEL-derived cell lines (BCBL-1, BC-1, and BC-3) in vitro and in vivo. An MTT assay and trypan blue exclusion assay revealed that irradiation significantly suppressed cell proliferation in the PEL cell lines in a dose-dependent manner, and induced apoptosis. The PEL cell lines were relatively radiosensitive compared with other hematological tumor cell lines (Raji, Jurkat, and K562 cells). Inoculation of the BC-3 cell line into the peritoneal cavity of Rag2/Jak3 double-deficient mice led to massive ascites formation, and subcutaneous injection of BCBL-1 led to solid lymphoma formation. Total body irradiation (4 Gy × 2) with bone marrow transplantation resulted in the complete recovery of both types of PEL-inoculated mice. These results suggest that total body irradiation with bone marrow transplantation can be successfully applied for the treatment of chemotherapy-resistant PEL.
