Anti-CD20-based therapy of B cell lymphoma: state of the art

Abstract

Over the last 5 years, studies applying the chimeric anti-CD20 MAb have renewed enthusiasm and triggered world-wide application of anti-CD20 MAb-based therapies in B cell non-Hodgkin's lymphoma (NHL). Native chimeric anti-CD20 and isotopelabeled murine anti-CD20 MAbs are currently employed with encouraging results as monotherapy or in combination with conventional chemotherapy and in consolidation of remission after treatments with curative intent (ie after/ in combination with high-dose chemotherapy and hematopoietic stem cell rescue). On the available experience, anti-CD20 MAb-based therapeutic strategies will be increasingly integrated in the treatment of B cell NHL and related malignancies.

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

“…Tumors reached a maximal size of 250 AE 100 mm 3 . Prior to imaging, mice were anesthetized with a mixture of 18.75 mg/kg ketamine hydrochloride (Ketamine 1000 Ceva, Ceva) and 0.5 mg/kg medetomidine hydrochloride (Domitor, Pfizer).…”

“…99m Tc-sdAbs were separated from unbound ( 99m Tc(H 2 O) 3 (CO) 3 ) þ via NAP-5 size exclusion chromatography (SEC; Sephadex, GE Healthcare). The eluate was filtered and the radiochemical purity was evaluated by iTLC (iTLC-SG, Pall Corporation).…”

“…3). The humanized mAb rituximab is the first approved anti-CD20 mAb and is being used as a first-line treatment against different forms of B-cell NHL (3). Rituximab given as a single agent shows response rates ranging from 50% to 80% (4)(5)(6)(7)(8), while in combination with chemotherapy, it shows response rates of more than 90%.…”

“…CD20 is expressed by over 90% of B-cell non-Hodgkin lymphoma (NHL; ref. 3). The humanized mAb rituximab is the first approved anti-CD20 mAb and is being used as a first-line treatment against different forms of B-cell NHL (3).…”

Ofatumumab

“…9 Many studies have demonstrated that crosslinking of CD20 with mAbs can recruit immunological molecules that trigger strong cytotoxic effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). 10 Moreover, CD20 has very high expression levels in patients with B-cell lymphoma, and there is almost no free CD20 in serum to compete with binding of mAbs. 11,12 These characteristics make CD20 an excellent target for B-cell related disease therapy.…”