CD22 is a B-cell-specific transmembrane
glycoprotein found on the surface of most B cells; it modulates B-cell function, survival and apoptosis. CD22 has emerged as an ideal target for
monoclonal antibody (mAb)-based
therapy of B-cell
malignancies including most
lymphomas and many
leukemias.
Epratuzumab, an anti-CD22 mAb, has been developed in various forms, including as an unlabeled (naked) mAb, as a radioimmunotherapeutic, as an
antibody drug conjugate (ADC), and as a vehicle for CD22-targeted nanoparticles. While clinical trials with unlabeled
epratuzumab have demonstrated modest results, its combination with
rituximab in phase II studies has been more encouraging. Based on the potential for CD22 to become internalized, CD22-targeted constructs carrying
radioisotopes or toxins have generated promising results.
Radioimmunotherapy, utilizing ⁹⁰Y-labeled
epratuzumab, was shown to be highly effective in patients with
follicular lymphoma, generating a complete response (CR) rate of 92 % and progression-free survival of more than 2 years. ADC
therapy is a promising therapeutic approach to B-cell
malignancies which includes the direct conjugation of mAbs with
cytotoxic agents. Phase II studies of
inotuzumab ozogamicin, an ADC which combines anti-CD22 mAb with
calicheamicin, an enediyne
antibiotic which mediates apoptosis, in patients with
acute lymphoblastic leukemia have produced an overall response rate (ORR) of greater than 50 % in treatment-refractory patients. Phase I trials of
moxetumomab pasudotox, an ADC which combines anti-CD22 with PE38, a fragment of Pseudomonas
exotoxin A, have been completed in
hairy cell leukemia with a ORR of 86 %. Finally, a review of CD22-targeted nanoparticles, that include a
doxorubicin-containing
lipid complex that uses synthetic high-affinity CD22
ligand mimetics as well as anti-CD22 mAb-coated pegylated liposomas doxorubin (
PLD), has demonstrated promising results in pre-clinical models of human
lymphoma. Moreover, novel anti-CD22 mAb that block CD22
ligand binding as well as second generation ADC that utilize biodegradable linkers and more potent toxins hold great hope for the future of CD22-targeted
therapeutics that may translate into better outcomes for patients with CD22-positive
malignancies.