Abstract

Recently, due to the application of hematopoietic stem cell transplantation and small molecule inhibitor, the survival of acute leukemia is prolonged. However, the 5 year survival rate remains low due to a high incidence of relapse. Immunotherapy is expected to improve the prognosis of patients with relapsed or refractory hematological malignancies because it does not rely on the cytotoxic mechanisms of conventional therapy. In this paper, the advances of immunotherapy in acute leukemia are reviewed from the aspects of Antibody including Unconjugated antibodies, Antibody-drug conjugate and Bispecific antibody, Chimeric Antigen Receptor (CARs), Immune checkpoint, Natural killer cells. The immunological features, mechanisms and limitation in clinic will be described.

Highlights

  • Acute leukemia is a kind of hematological malignancy with high mortality and poor prognosis and it requires a complex and highly diversified treatment because of its wide prognostic heterogeneity

  • This study focused on the naked monoclonal antibodies, antibody-drug conjugate (ADC), bispecific T cell engager (BiTE), chimeric antigen receptor (CAR) T/NK cell, immune checkpoint inhibitor/immune agonist, etc

  • After allogeneic hematopoietic stem cell transplantation, CSL362 combined with donor-derived NKs effectively dissolved these cells, suggesting that CSL362 can be used as a promising therapy for chemotherapy and transplantation [45]

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Summary

INTRODUCTION

Acute leukemia is a kind of hematological malignancy with high mortality and poor prognosis and it requires a complex and highly diversified treatment because of its wide prognostic heterogeneity Traditional treatments such as chemotherapy and hematopoietic stem cell transplantation make patients obtain complete remission, patients will eventually develop relapse and resistance, leading to disease progression. GO has shown a narrow therapeutic window in early clinical studies, recent reports have proved that the improved dose regimen of GO combined with induced chemotherapy was safe and provided significant survival value for AML patients. After allogeneic hematopoietic stem cell transplantation, CSL362 combined with donor-derived NKs effectively dissolved these cells, suggesting that CSL362 can be used as a promising therapy for chemotherapy and transplantation [45] Another antibody SL-101, which is a novel antibody-conjugate comprising an anti-CD123 single-chain Fv fused to Pseudomonas exotoxin A, is in the preclinical study [46]. It is expected to improve the survival of patients if it is used in first-line therapy especially before allogeneic hematopoietic stem cell transplantation because of Epratuzumab’s ability to reduce MRD levels [66]

Results
Phase Results
CONCLUSIONS
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