Therapeutic Advances in Immunotherapies for Hematological Malignancies

Abstract

Following the success of immunotherapies such as chimeric antigen receptor transgenic T-cell (CAR-T) therapy, bispecific T-cell engager therapy, and immune checkpoint inhibitors in the treatment of hematologic malignancies, further studies are underway to improve the efficacy of these immunotherapies and to reduce the complications associated with their use in combination with other immune checkpoint inhibitors and conventional chemotherapy. Studies of novel therapeutic strategies such as bispecific (tandem or dual) CAR-T, bispecific killer cell engager, trispecific killer cell engager, and dual affinity retargeting therapies are also underway. Because of these studies and the discovery of novel immunotherapeutic target molecules, the use of immunotherapy for diseases initially thought to be less promising to treat with this treatment method, such as acute myeloid leukemia and T-cell hematologic tumors, has become a reality. Thus, in this coming era of new transplantation- and chemotherapy-free treatment strategies, it is imperative for both scientists and clinicians to understand the molecular immunity of hematologic malignancies. In this review, we focus on the remarkable development of immunotherapies that could change the prognosis of hematologic diseases. We also review the molecular mechanisms, development processes, clinical efficacies, and problems of new agents.

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review

“…With regard to the GPRC5D-associated AEs, further research is needed to assess the effectiveness of dose modification strategies, including reduced dose frequency and fixed duration dosing, as well as other mitigation measures, to more optimally balance on-target, off-tumor toxicity with the promising efficacy observed with these therapies. In addition to these trials, CAR-natural killer, bispecific-natural killer cell engager, and antibody-drug conjugate therapies may also offer advancements in treatment outcomes [65][66][67][68].…”

SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection

“…In recent years, the application of proteasome inhibitors, immunomodulation, and immunotherapy has led to significant advances in the treatment of first-line and relapsed refractory (R/R) MM, greatly improving patient objective response rates (ORR) and durable complete remission rates (CR) [ 4 ]. In particular, immunotherapies, including CD38 monoclonal antibody and BCMA Chimeric antigen receptor (CAR) T cell therapy, have shown stunning results in patients with MM [ 5 , 6 ]. However, MM can still recur incurably.…”

Mesenchymal stromal cells in myeloid malignancies: Immunotherapeutic opportunities

“…Immune checkpoints are crucial in regulating T-cell antigen responses. However, ICIs amplify the killer cells' cytotoxic capabilities against myeloid neoplastic leukemic cells, which showcases the potential of using ICIs to boost the immune system's capacity to combat myeloid neoplasms [ [200] , [201] , [202] ].…”

“…A promising treatment for myeloid malignancies is the chimeric antigen receptor T (CART) cells adoptive cellular immunotherapy [ 202 , 210 , 211 ]. CARs are genetically modified receptors composed of an extracellular domain, a transmembrane domain, and an intracellular T cell activation and co-stimulation signaling domain.…”