Despite new insights in molecular features of leukemic cells and the availability of novel treatment approaches and drugs, acute myeloid leukemia (AML) remains a major clinical challenge. In fact, many patients with AML relapse after standard therapy and eventually die from progressive disease. The basic concept of leukemic stem cells (LSC) has been coined with the goal to decipher clonal architectures in various leukemia‐models and to develop curative drug therapies by eliminating LSC. Indeed, during the past few years, various immunotherapies have been tested in AML, and several of these therapies follow the strategy to eliminate relevant leukemic subclones by introducing LSC‐targeting antibodies or LSC‐targeting immune cells. These therapies include, among others, new generations of LSC‐eliminating antibody‐constructs, checkpoint‐targeting antibodies, bi‐specific antibodies, and CAR‐T or CAR‐NK cell‐based strategies. However, responses are often limited and/or transient which may be due to LSC resistance. Indeed, AML LSC exhibit multiple forms of resistance against various drugs and immunotherapies. An additional problems are treatment‐induced myelotoxicity and other side effects. The current article provides a short overview of immunological targets expressed on LSC in AML. Moreover, cell‐based therapies and immunotherapies tested in AML are discussed. Finally, the article provides an overview about LSC resistance and strategies to overcome resistance.

中文翻译：

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针对急性髓系白血病中的白血病干细胞的基于细胞和抗体介导的免疫疗法：观点和未解决的问题。

尽管对白血病细胞的分子特征有了新的认识，并且有了新的治疗方法和药物，急性髓系白血病（AML）仍然是一个重大的临床挑战。事实上，许多 AML 患者在标准治疗后复发并最终死于疾病进展。白血病干细胞 (LSC) 的基本概念是为了破译各种白血病模型中的克隆结构并通过消除 LSC 来开发治疗药物的目标而创造的。事实上，在过去的几年里，各种免疫疗法已经在 AML 中进行了测试，其中一些疗法遵循通过引入 LSC 靶向抗体或 LSC 靶向免疫细胞来消除相关白血病亚克隆的策略。这些疗法包括新一代 LSC 消除抗体构建体、检查点靶向抗体、双特异性抗体以及基于 CAR-T 或 CAR-NK 细胞的策略。然而，响应通常是有限的和/或短暂的，这可能是由于 LSC 阻力造成的。事实上，AML LSC 对各种药物和免疫疗法表现出多种形式的耐药性。另一个问题是治疗引起的骨髓毒性和其他副作用。本文简要概述了 AML 中 LSC 表达的免疫靶点。此外，还讨论了在 AML 中测试的细胞疗法和免疫疗法。最后，本文概述了 LSC 阻力以及克服阻力的策略。