The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T- cell therapy.
Inotuzumab ozogamicin (InO), an anti-CD22 antibody conjugated to calicheamicin, has shown significantly higher rates of remission, minimal residual disease negativity, and HSCT versus standard chemotherapy in treating relapsed/refractory (R/R) ALL.
Immunotherapies such as chimeric antigen receptor-modified T-cells, the bispecific T-cell-engaging antibody targeting CD19 (blinatumomab), and the antibody-drug conjugate targeting CD22 (inotuzumab) have shown safety and exceptional activity even in advanced ALL, and the efficacy of these agents has been observed irrespective of patient age.
Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia.
CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL) patients.
In the USA, a phase III trial evaluating inotuzumab ozogamicin in combination with frontline chemotherapy in adults with newly diagnosed B-cell ALL has recently been initiated and inotuzumab ozogamicin is under phase II evaluation in childhood CD22-positive B-cell ALL.
We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants that could play role in the pathogenesis of pre-B ALL in Turkish children.
The anti-leukemic activity of this RTM against BPL xenograft clones derived from CD22ΔE12(+) leukemia patients provides the preclinical proof-of-concept that correcting the CD22ΔE12 defect with rationally designed CD22 RTMs may provide the foundation for therapeutic innovations that are needed for successful treatment of high-risk and relapsed BPL patients.
These characteristics make CD22 an excellent potential therapeutic target in patients with relapsed and chemotherapy-refractory ALL, although cases with MLL rearrangement require close study to exclude the presence of a CD22-negative blast population.
Our data uniquely indicate that CD22ΔE12 is a candidate driver lesion responsible for the activation of MAPK and PI3-K pathways in aggressive forms of B-lineage ALL.
HA22 is composed of an Fv that binds to CD22 fused to a portion of Pseudomonas exotoxin A. HA22 is very active in drug-resistant hairy cell leukemia but is less active in children with acute lymphoblastic leukemia.
An immunotoxin (IT) constructed with RFB4, a murine anti-CD22 monoclonal antibody, and the "deglycosylated" A chain of ricin has shown activity at safe doses in patients with non-Hodgkin lymphoma and in children with acute lymphoblastic leukemia.
The aim of our study was to evaluate in a large series of cases of acute lymphoblastic leukemia (ALL) the expression of specific antigens, CD19, CD20, CD22, and CD33, for which MoAbs are available for clinical use.
We report on a case of a 30-year-old male with acute B-lymphoblastic leukemia (B-ALL) with immunophenotype CD19(+), CD22(+), CD20(+), CD10(+), with aberrant expression of CD13 and CD117, and IgH gene rearrangements.
The anti-CD19 and anti-CD22 ITs should have anti-tumor activity against childhood B-lineage ALL since both target antigens are expressed on the surface of these cells.
A newly established human leukemia cell line, OM9;22, is reported, with B-precursor immunophenotype (CD10+ CD19+ CD22+ HLA- DR+ C mu-) and CD13 antigen, originated from a 19-year-old female patient with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL).
All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig).