Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia

Abstract

Targeted agents are increasingly used for the therapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO) is the first antibody-drug conjugate (ADC) approved for induction therapy of AML. When used in fractionated doses, GO combined with the conventional cytarabine/anthracycline-based induction chemotherapy significantly improves the outcome of previously untreated AML patients. Single-agent GO is effective and safe for AML patient ineligible for intensive chemotherapy. Multiple combination regimens incorporating GO have also been recommended as potential alternative options. In addition, several novel ADCs targeting CD33, CD123 and CLL-1 are currently undergoing preclinical or early clinical investigations. In this review, we summarized the efficacy and limitations of GO as well as novel ADCs for adult AML patients.

Myeloid-derived suppressor cells—new and exciting players in lung cancer

“…Fultang et al identified CD33 as a therapeutic target on peripheral and infiltrating MDSCs across cancer subtypes by RNA-sequencing and flow cytometry. Gemtuzumab ozogamicin (GO), a humanized anti-CD33 IgG4 mAb conjugated to a cytotoxic agent N-acetyl gamma calicheamicin via an acid-labile hydrazone linker [136], has been successfully used as a treatment for acute myeloid leukemia [137]. The argeting of MDSCs with GO leads to GO internalization, increased p-ATM, and MDSC cell death.…”

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

“…The ELN classification includes molecular genetic abnormalities that should be part of the routine clinical evaluation of AML patients [352,353], but it is still regarded as controversial whether, for example, the detection of a KIT mutation will worsen the prognosis of patients with t(8;21) or inv (16) [359]. This drug may also be used in elderly patients up to age 70 [360,361]. Third, CPX-351 is encapsulated in nanoscale liposomes of cytarabine and daunorubicin at a synergistic 5:1 molar ratio; this agent may become useful even for high-risk patients and may also be used in elderly patients [362,363].…”

“…• Lenalidomide inhibits the differentiation of nursing-like cells into an M1 phenotype with the high release of CCL2, IGF1, CXCL12, and HGF1 and has the ability to support T-cell proliferation [152,404]. • Pomalidomide activates RhoA, enhances F-actin formation, and increases cell migration [360].…”

“…[152,360,376,[396][397][398][399][400][401][402][403][404][405][406][407][408]. The most important conclusion from CLL research is that IMiDs' anticancer effects are very complex, which is unsurprising considering the complex effects of these drugs on intracellular regulation and extracellular crosstalk between a wide range of cells.…”

Increased PD-1+Tim-3+ exhausted T cells in bone marrow may influence the clinical outcome of patients with AML

“…Although increasing findings have improved understanding of the pathogenesis of AML, standard therapies have not changed for over 30 years. With the recent development of targeted and immunotherapy, a number of ongoing studies aim to produce novel AML therapies, including conventional cytotoxic chemotherapies, genetic and epigenetic targeted therapies, and immunotherapies [3][4][5][6]. The T cell immune status of patients is an important factor related to the prognosis of leukemia [7][8][9][10][11].…”