-CD33 is expressed on the majority of AML cells, making it a promising target. However, CD33 is also found on normal myeloid cells, including progenitor cells, leading to concerns about myeloablation and prolonged cytopenias if CAR-T cells target healthy cells. 283, 284 -CD123 (IL-3 Receptor Alpha Chain) is another common target in AML. It is expressed on AML blasts and leukemic stem cells (LSCs). However, like CD33, CD123 is also present on normal hematopoietic stem and progenitor cells, posing similar toxicity risks. 285, 286 -FLT3 is a receptor tyrosine kinase often mutated in AML, leading to its overexpression in AML cells. CAR-T cells targeting FLT3 are being explored, but concerns remain regarding ontarget effects on normal hematopoietic cells. 287, 288 -CLL-1 (CLEC12A) is expressed on AML cells and LSCs, but not on normal hematopoietic stem cells, making it a potentially safer target. However, its expression is not universal across all AML cases. 289, 290 -To address the issue of antigen heterogeneity, dual-targeting CAR-T cells that recognize two different antigens (e.g., CD33 and CD123) are being developed. These approaches aim to reduce the likelihood of AML escape via antigen loss. Combining CAR-T therapy with other treatments like checkpoint inhibitors, hypomethylating agents, or kinase inhibitors is being explored to enhance CAR-T cell efficacy and persistence while reducing toxicities. • CAR-T | Colon cancer CAR-T cell therapy application to solid tumors like colon cancer poses significant challenges: (i) major hurdle in CAR-T therapy for colon cancer is identifying antigens that are highly expressed on tumor cells but not on normal tissues, to avoid on-target, off-tumor toxicity; (ii) tumor microenvironment in colon cancer is highly immunosuppressive; (iii) colon cancer is characterized by heterogeneity in antigen expression; (iv) colon cancer cells can downregulate antigen presentation and secrete immunosuppressive factors, making it difficult for CAR-T cells to recognize and attack them. Despite these challenges, several antigens and strategies are being investigated for CAR-T cell therapy in colon cancer: