Novel Therapeutic Strategies “Highlight Need to Understand Underlying Molecular Processes” in Hematologic Cancers

Two review articles recently published just days apart argue that while novel therapeutic strategies are changing the prognosis for many hematologic malignancies, the proliferation of these agents highlights a need to better understand the molecular processes underlying these disorders.

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,” Ayako Nogami and Koji Sasaki of the Tokyo Medical and

Dental University write in a review published in the International Journal of Molecular Sciences on Sept. 29.

Specific issues that need to be addressed, they write, include developing strategies to overcome the “sophisticated antigen-escape mechanisms” that some tumors develop and advancing understanding of the role of the tumor and bone marrow microenvironments in the onset and recurrence of hematologic cancers.    

New classes of targeted agents and their mechanisms of action “demonstrate that we are on the cusp of a new molecular era” in the treatment of B-cell lymphomas, but the success of these new agents “will require a deeper understanding of the processes underlying lymphomagenesis,” Afua Adjeiwaa Mensah of the Institute of Oncology Research in Bellinzona, Switzerland, and Patrizia Mondello of the Mayo Clinic write in a review published in the Journal of Clinical Medicine on Oct. 1.

Although advances in genomics and high-resolution genetic technology “have rewired preclinical and clinical efforts in understanding cancer, paving the way for precision therapies,” much more work needs to be done to decipher the molecular fingerprints of B-cell lymphomas before routine personalized medicine can become a reality for this class of cancers, they write.

Bispecific T-cell engagers (BiTEs) and similar agents such as bispecific killer-cell engagers (BiKEs), dual-affinity retargeting agents (DARTs), and trispecific killer-cell engagers (TriKEs) offer advantages in that they are not affected by tumor downregulation of MHC and as synthetic products “do not need to be tailored for each patient,” Nogami and Sasaki write. Mensah and Mondello agree that BiTEs and similar agents “offer an off-the-shelf and more immediate alternative” to CAR T therapy, but note that these agents’ mechanism of action – reliance on the patient’s T cells to kill tumor cells – may also be their weakness, as it renders them unsuitable when T cell activity is poor.

  • Mensah AA, Mondello P. Harnessing the Molecular Fingerprints of B Cell Lymphoma for Precision Therapy. J Clin Med. 2022;11(19):5834. Published 2022 Oct 1. doi:10.3390/jcm11195834
  • Nogami A, Sasaki K. Therapeutic Advances in Immunotherapies for Hematological Malignancies. Int J Mol Sci. 2022;23(19):11526. Published 2022 Sep 29. doi:10.3390/ijms231911526

Tags: bispecific t cell engagers, bite, Immunity, transplantation, CAR T, BiTEs, Chemo, malignancy, hematologic, Lymphocytes, strategies, CAR T-cell, transplantation and cellular therapy, transplatation, tumors, bone marrow, T cells, bispecific, hematopoietic cell tranplanta, stem cell transplant, lymphona, molecules, molecular modeling