Immunotherapy in chronic lymphocytic leukemia: advances and challenges

Abstract

Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treatment modalities and offering substantial benefits to patient outcomes. This review endeavors to synthesize and scrutinize the efficacy, merits, and limitations of the current immunotherapeutic strategies for CLL. The aim is to inform the selection of optimal treatment regimens tailored to individual patient needs. Furthermore, the review juxtaposes various therapeutic combinations to elucidate the comparative advantages of each approach, with the ultimate objective of enhancing patient prognosis and quality of life.

Keywords: Antibody; Chronic lymphocytic leukemia; Combination therapy; Immune cell; Immunotherapy.

Fig. 1

The immunotherapy of CLL mainly includes the following six aspects. They are Chimeric CD20 monoclonal antibody therapy; CAR cell therapy; Bispecific antibody therapy; Combination therapy with antibody drugs; γδ T cell therapy; and BAK cell therapy. We will discuss five aspects: mechanism, efficacy, side effects and safety, resistance mechanism, and future directions

Fig. 2

The reaction between anti-CD20 monoclonal antibody and CLL cells. CD20 mAbs mainly induce the death of tumor cells expressing CD20 molecules through three mechanisms, namely antibody-dependent cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct effect killing of tumor cells caused by the binding of antibodies to CD20 molecules. In addition, this picture shows the expression of CD20 in normal B cells and CLL cells. Normal B cells typically express high-density CD20 molecules, while CLL cells have lower levels of CD20 expression. This difference may influence the therapeutic efficacy of CD20 monoclonal antibodies. BAFF-R, BAFF-Receptor

Fig. 3

The reaction between CAR cells and CLL cells. Mainly including CAR-T cells, CAR-NK cells, and CAR-M cells