This IP exhibits a significant advancement in cancer immunotherapy. It encompasses a novel scFv designed to specifically target CD33, a surface antigen commonly expressed in hematologic cancers such as leukemia, myeloma, and lymphoma. This scFv serves as a fundamental component in various therapeutic modalities, such as chimeric antigen receptor (CAR) T-cell and natural killer (NK) cell therapies. Hematologic cancers pose significant challenges in treatment and often require targeted therapeutic approaches. The scFv targeting CD33 offers a promising solution by enabling the development of highly specific immunotherapies. CAR-T cells and CAR-NK cells engineered with this scFv can selectively recognize and eliminate CD33-expressing cancer cells while sparing healthy tissues, thus potentially improving treatment efficacy and minimizing adverse effects associated with traditional therapies. The IP’s innovative design features an alternative linker and an unexpected reverse orientation of the variable heavy (VH) and variable light (VL) chains, potentially conferring advantages in terms of binding affinity and epitope recognition. This enhances the specificity and effectiveness of CD33-targeted therapies, offering improved treatment outcomes for patients. The applications of the scFv targeting CD33 are extensive and includes both immediate and future uses. In the short term, it can be incorporated into CAR-T cell and CAR-NK cell therapies for the treatment of CD33-positive hematologic cancers. Additionally, the scFv may find utility in the development of other CD33-targeted therapies—including bispecific antibodies and antibody-drug conjugates—expanding its therapeutic potential across a broader range of malignancies. Biopharmaceutical companies involved in cancer immunotherapy may express interest in licensing this innovative technology. Further development of the scFv targeting CD33 involves in vivo assays to evaluate its efficacy against human hematologic cancer xenografts in animal models. Ongoing research efforts will focus on optimizing the scFv sequence and engineering CAR-T and CAR-NK cells expressing this scFv for preclinical and clinical studies. These endeavors aim to establish proof of concept and advance the technology towards eventual clinical translation.