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We review the state-of-the-art in bone and marrow tissue engineering (BMTE) and hematological cancer tissue engineering (HCTE) in light of the recent interest in bone marrow environment and pathophysiology of hematological cancers. This review focuses on engineered BM tissue and organoids as in vitro models of hematological cancer therapeutics, along with identification of BM components and their integration as synthetically engineered BM mimetic scaffolds. In addition, the review details interaction dynamics of various BM and hematologic cancer (HC) cell types in co-culture systems of engineered BM tissues/phantoms as well as their relation to drug resistance and cytotoxicity. Interaction between hematological cancer cells and their niche, and the difference with respect to the healthy niche microenvironment narrated. Future perspectives of BMTE for in vitro disease models, BM regeneration and large scale ex vivo expansion of hematopoietic and mesenchymal stem cells for transplantation and therapy are explained. We conclude by overviewing the clinical application of biomaterials in BM and HC pathophysiology and its challenges and opportunities. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptors (CARs) targeting CD19 have emerged as a new treatment for hematological malignancies. As a "living therapy", CARs can precisely target and eliminate tumors while proliferating inside the patient's body. Various preclinical and clinical studies are ongoing to identify potential CAR-T cell targets for acute myeloid leukemia (AML). We shed light on the continuing efforts of CAR development to overcome tumor escape, exhaustion, and toxicities. Furthermore, we summarize the recent progress of a range of putative targets exploring this unmet need to treat AML. Lastly, we discuss the advances in preclinical models that built the foundation for ongoing clinical trials. Engineered T cells expressing chimeric antigen receptors (CARs) on their cell surface can redirect antigen specificity. This ability makes CARs one of the most promising cancer therapeutic agents. CAR-T cells for treating patients with B cell hematological malignancies have shown impressive results. Clinical manifestation has yielded several trials, so far five CAR-T cell therapies have received US Food and Drug Administration (FDA) approval. However, emerging clinical data and recent findings have identified some immune-related toxicities due to CAR-T cell therapy. Given the outcome and utilization of the same proof of concept, further investigation in other hematological malignancies, such as leukemias, is warranted. This review discusses the previous findings from the pre-clinical and human experience with CAR-T cell therapy. Additionally, we describe recent developments of novel targets for adoptive immunotherapy. Here we present some of the early findings from the pre-clinical studies of CAR-T cell modification through advances in genetic engineering, gene editing, cellular programming, and formats of synthetic biology, along with the ongoing efforts to restore the function of exhausted CAR-T cells through epigenetic remodeling. We aim to shed light on the new targets focusing on acute myeloid leukemia (AML). [ABSTRACT FROM AUTHOR]