Translational Medicine in Action: Anti-CD20 Therapy in Lymphoma

Abstract

The introduction of rituximab for B cell lymphoma in the late 1990s inaugurated a new era of cancer therapy showcasing mAbs. mAbs are in principle an amalgamation of two characteristics of a perfect anticancer drug. First, rituximab is a therapy targeted to the tumor cell, but it carries fewer side effects than does chemotherapy. Second, with its ability to directly engage the host immune system, it could potentially elicit longer lasting anticancer immunity, although this remains to be proven. This review highlights the fundamental scientific discoveries that allowed the development of clinically successful anti-CD20 mAbs. Since the approval of rituximab, a considerable amount of work has been undertaken by different groups trying to understand the workings and limitations of anti-CD20s. All of these efforts will be critical in designing new mAbs to CD20 and other targets and, ultimately, of anticancer mAbs that will improve on, or even replace, chemotherapy.

Theranostic Radiolabeled Anti-CD20 sdAb for Targeted Radionuclide Therapy of Non-Hodgkin Lymphoma

“…Internalization of residualizing radiometals traps these radioisotopes intracellulary, potentially leading to increased retention of therapeutic radiation in tumor (30). CD20 internalization is highly variable and depends on the targeted cell type, the presence of coreceptors, the nature of the ligand and the targeted epitope (36). It is remarkable that although 177 Lu-DTPA-sdAb 9077 internalized better than 9079 in vitro, this was not translated into a better tumor uptake in vivo.…”

Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity

“…16 In the past decades, more and more novel anti-CD20 mAbs have been developed for improving the therapeutic efficacy against naïve and resistant NHLs. 3,8,14 Presently, anti-CD20 mAbs can be grouped into two major categories (type I and type II) with different tumor-killing mechanisms, including CDC, ADCC, and direct induction of PCD. 27 It is well established that cancer is usually multifactorial in nature, involving various redundant disease-mediating ligands and receptors, as well as crosstalk between signal cascades.…”

“…1,2 Depending on the subtype of B-cell NHL, the disease can pursue an indolent course spanning years, such as in follicular lymphoma, or it can present aggressively during several weeks or months, such as in diffuse large B-cell lymphoma. 3 Although the "watch and wait" approach is acceptable in asymptomatic patients with indolent NHL, patients with more aggressive subtypes require immediate and effective treatments. 3,4 Traditional therapies for NHL, including chemotherapy and radiotherapy, are limited because of serious harmful side effects.…”

“…3 Although the "watch and wait" approach is acceptable in asymptomatic patients with indolent NHL, patients with more aggressive subtypes require immediate and effective treatments. 3,4 Traditional therapies for NHL, including chemotherapy and radiotherapy, are limited because of serious harmful side effects. 2,3 In the past decades, a variety of basic and groundbreaking discoveries paved the way for the development of mAbs, the theoretical "magic bullets", which could specifically identify and kill malignant cells, thereby reducing the detrimental side effects to normal tissues.…”

“…3,4 Traditional therapies for NHL, including chemotherapy and radiotherapy, are limited because of serious harmful side effects. 2,3 In the past decades, a variety of basic and groundbreaking discoveries paved the way for the development of mAbs, the theoretical "magic bullets", which could specifically identify and kill malignant cells, thereby reducing the detrimental side effects to normal tissues. 5,6 CD20 is a B-cell differentiating antigen, which selectively expressed on the surface of mature and malignant B-cells, but not immature B-cells or plasma cells.…”