ReviewAcute myeloid leukemia and novel biological treatments: Monoclonal antibodies and cell-based gene-modified immune effectors
Introduction
Nowadays, the main challenge for the scientific community working on AML concerns the high rates of relapse, accounting for 50–70% within the first 3 years after achievement of complete remission [1], with better survival trend for pediatric than adult population [2]. Allogeneic hematopoietic stem cell transplantation is adopted as post-remission therapy in high-risk patients, but it still carries the major drawback of high transplant-related mortality. A growing body of evidence reveals that the limitedness of the current chemotherapeutic regimens mainly lies in the inability of properly eradicating AML and in particular the leukemic stem cells (LSCs) present in the bulk of leukemic cells [3], [4]. Therefore, researchers are moving toward more targeted strategies, investing in the immunotherapy field as a potential fertile ground complementary to standard chemotherapy. Here we compare and review passive immunotherapy approaches using both monoclonal antibodies (mAb) and cellular and gene-therapies.
Section snippets
State of the art of mAb therapy for AML
Since the early 80's, the mAb technology has been one of the first attempts of biomedical sciences in developing targeted therapeutics. However, initial studies highlighted the limitations of using unconjugated mAbs in rapidly proliferative diseases. Thus, mAbs were manipulated in the Fc portion to better stimulate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Additionally, bi-specific mAbs or mAbs conjugated with cytotoxic drugs were generated,
Adoptive T cell therapy
Adoptive cell therapy (ACT) harnesses the ability to mount specific responses of the cellular immune system by transferring ex vivo expanded autologous or allogeneic T cells into tumor-bearing patients. Indeed, donor lymphocyte infusion (DLI) have been largely used in patients with hematological malignancies. However, the limited activity of DLI in AML patients is also associated with a high incidence (40–60%) of graft versus host disease (GVHD) [25]. Thus, new therapeutic strategies have been
Conclusions
Improvements in the mAb design and the efficient transfer of CARs together with a feasible manufacturing practice (GMP) strategy to select and propagate CAR-expressing cells are currently among the newest therapeutic approaches for the treatment of resistant forms of AML. The choice of the target antigen will be detrimental in defining the best mAb or CAR to be used in this window of treatment in order to eradicate the disease while sparing the normal tissues. In the near future, we envision
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