Antibody and Cellular-Based Therapies for Pediatric Acute Lymphoblastic Leukemia: Mechanisms and Prospects

Abstract

<b><i>Background:</i></b> Acute lymphoblastic leukemia (ALL) is one of the most commonly diagnosed cancers in children. Despite enormous efforts to treat ALL over the past decade, the intensity of conventional chemotherapeutic strategies has reached the tolerance limit. Among various recently developed therapeutic approaches, antibody and cellular-based therapies showed less toxicity and better curative effect. <b><i>Summary:</i></b> Due to advanced mechanistic actions, these innovative therapies have provided durable responses and long-term survival in eradicating pediatric ALL, especially patients with refractory/relapsed ALL. Owing to these aspects, herein, we emphasize the mechanisms of action and application status of antibodies targeting tumor antigens, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells. <b><i>Key Messages:</i></b> The significant prospects and challenges are discussed, highlighting the innovative immunotherapies to deal with ALL. Together, this review will summarize the progress of antibody and cellular-based therapies for pediatric ALL, which may promote further research on antibody-based biopharmaceutics.

A Review of Acute Lymphocytic Leukemia (ALL) in the Pediatric Population: Evaluating Current Trends and Changes in Guidelines in the Past Decade

“…The cost of a single infusion of CAR T-cell therapy is about $475,000 in the US, with a charge waiver if treatment fails one month following the infusion. The actual cost of treatment, including supportive care and management of toxicities and complications, such as chronic hypo-gammaglobulinemia, is estimated to reach $1,000,000 [ 21 , 37 , 79 ].…”

“…In present times, immunotherapy is one of the innovative treatment choices against cancer. Owing to their ability to modulate the host immune system while attacking cancer cells, antibody and cellular-based therapies have gained enormous interest from academic researchers and pharmaceutical entrepreneurs in treating various malignant tumors [ 37 ].…”

A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation

“…By switching therapies sooner before complete resistance has evolved, the physician and patient retain the option for switching to an adaptive therapy. While models of extinction therapy have been developed ( Gatenby et al, 2020a ), clinical evidence is sparse but supported by the standard of care multistep curative treatment in Pediatric Acute Lymphocytic Leukemia ( Li et al, 2022 ), by two case studies involving cure in patients with metastatic breast cancer ( Chue and La Course, 2019a ; Chue and La Course, 2019b ), and an ongoing clinical trial for patients with pediatric rhabdomyosarcoma ( Reed et al, 2020 ).…”

CircRNA: a rising star in leukemia

“…It is an aggressive and heterogeneous disease characterized by rapid proliferation and arrested differentiation of medulloblastoma in the peripheral blood, bone marrow, and other tissues ( Shapoorian, Zalpoor & Ganjalikhani-Hakemi, 2021 ; Xiang et al, 2022 ). ALL is a highly-aggressive hematological disease ( Li et al, 2022 ; Xin et al, 2022 ). ALL patients are characterized by an abnormal proliferation and aggregation of lymphocytes in the bone marrow.…”