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B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes.  Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST).  However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients.  Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.

The manner by which cancers evade the immune response is not well-understood. What is known is that the manner is an active process that regulates immune responses employing at least two types of suppressive cells, myeloid-derived suppressive cells and regulatory T cells (Tregs), a key subset of CD4+ T cells that controls peripheral tolerance to self- and allo-antigens. Tregs are considered to play a key role in the escape of cancer cells from anti-tumor effector T cells.

The development of precision medicine approaches for DLBCL (Diffuse Large B Cell Lymphoma) is complicated by its genetic, phenotypic and clinical heterogeneity. Current classification methods do not fully explain the observed differences in clinical outcomes to current chemotherapy and targeted therapy. Therefore, better analytical methods to classify and predict DLBCL patients’ treatment response are needed.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma and consists of three subtypes: activated B-cell (ABC), germinal center B-cell (GBC), and primary mediastinal B-cell (PMB). Despite advances in the front-line therapy for DLBCL, approximately one-third of patients will relapse. Substantially worse outcomes have been reported for patients diagnosed with ABC DLBCL and treated with standard chemoimmunotherapy, suggesting the need for novel strategies that improve treatment outcomes.

Immortalization of plasma cells leads to plasma cell malignancy diseases such as multiple myeloma (MM). B-cell maturation antigen (BCMA) is a protein that is preferentially expressed by malignant and normal B cells and plasma cells, butnot on other cells in the body. This limited expression profile suggests that BCMA is a promising target for anticancer therapeutics for cancers in which there is excess production of plasma cells and B cells. 

Targeting the CD22 receptor of B-cells with chimeric antigen receptor (CAR)-T cells has been a promising new therapy to treat B-cell malignancies in clinical trials, inducing remission in 70% of patients with relapsed acute lymphoblastic leukemia (ALL). However, diminished CD22 expression on B-cell surface can lead to relapse and decreased remission duration, which may be prevented through increasing CAR-T affinity towards CD22. 

Treatment of B-cell acute lymphoblastic leukemia (ALL) and lymphoma using chimeric antigen receptors (CARs) targeting B-cell surface protein CD19 has demonstrated impressive clinical results in children and young adults. Despite the promising results from CD19 CAR therapy, up to 40% of patients, who initially achieve remission, eventually relapse. Relapse or non-response to CD19-directed CAR therapy may be due to low or diminished CD19 expression. Such patients would be predicted to benefit from CAR therapies targeting other B-cell surface proteins, such as CD22.

Patients with chemotherapy-refractory, diffuse large B-cell lymphoma (DLBCL) have poor prognoses. CD19 and CD20 are promising targets for the treatment of B-Cell malignancies. However, despite the initial promising results from anti-CD19 CAR therapy, only 30-35% of patients with DLBCL achieve remissions lasting longer than 2-3 years after anti-CD19 CAR T-cell therapy. Relapse and non-response are likely due to diminished CD19 expression after anti-CD19 therapy and low expression of CD19 in some lymphomas. 

CD22 is a common cell surface glycoprotein expressed in B-cells and present in B-cell lymphomas; e.g., hairy cell leukemia (HCL), non-Hodgkins lymphoma (NHL), chronic lymphoblastic leukemia (CLL), and other cancers. It is therefore a target for cancer immunotherapy. Conjugation of anti-CD22 monoclonal antibodies with toxins or drugs has shown promise in clinical trials. However, all monoclonal anti-CD22 antibodies used in clinical trials are of murine origin.

Mantle cell lymphoma (MCL) is a group of aggressive B-cell lymphomas displaying heterogeneous outcomes after treatment.  Some patients have the slowly progressing disease that does not require immediate treatment, while others have a disease that rapidly progresses despite highly aggressive treatment. A number of prognostic tools have been described to determine whether patients have slow or rapidly progressing diseases, including the mantle cell lymphoma International Prognostic Index (MIPI) and biomarkers, such as KI-67.