About this Research Topic
Antibody therapeutics directed against cancer-associated targets or immune checkpoints have improved the overall survival of patients in several types of cancer. Hitherto, such therapies have displayed limited clinical efficacy in myeloid malignancies and only gemtuzumab-ozogamicin, an antibody targeting CD33 conjugated to a cytotoxic payload, has been approved for acute myeloid leukemia (AML). However, CD33 is also present on normal myeloid progenitors and CD33-directed therapies are associated with severe toxicities.
Myeloid malignancies, that include but are not limited to AML, chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), and myeloproliferative disorders (MPD) are all believed to be maintained and propagated by a rare type of chemotherapy-resistant cell population with self-renewal capacity, often referred to as leukemia stem cells (LSCs). Antibody-based therapeutic approaches for these diseases have mainly focused on targeting cell surface proteins upregulated on LSCs by blocking their function and/or to facilitate innate immune cell killing of the malignant cells. Examples of such LSC-associated antigens include CD123, CD47, CD70, IL1RAP, CLL-1, CD99, TIM-3, and CD98, which all have been successfully explored as therapeutic targets in preclinical models of myeloid leukemia using monoclonal antibodies. Recently, early clinical data suggested that therapeutic antibodies targeting the immune checkpoint CD47 for macrophages have anti-leukemic activity in AML, the most common acute leukemia among adults. Moreover, antibody-based targeting of CD70 in AML has shown promising therapeutic effects in a recent phase I/II clinical trial. In addition to activating macrophages, monoclonal antibodies have been developed to activate Natural killer (NK) cells, an innate immune cell population that is suppressed in AML. Strategies to alter the characteristics of antibodies, such as modified glycosylation patterns, which enhance affinity to Fc receptors have also been developed to enhance their activity. Another approach to direct immune-responses against myeloid leukemia cells is the development of bispecific antibodies that crosslink the malignant cells with either T-cells or NK- cells. Moreover, the development of immunocytokines, which are fusion proteins between antibodies and cytokines have been developed to bolster immune-mediated anti-leukemic activity.
The scope of this Research Topic is to gather a comprehensive list of articles related to “Antibody therapeutics for myeloid malignancies”. The Research Topic will cover various aspects spanning from basic, translational and clinical research related to antibody therapeutics in these diseases. We welcome the submission of Original Research Articles, Reviews, Mini-Reviews, and Clinical Trials covering, but not limited to, the following topics:
1. Research characterizing molecular targets for antibody-based therapeutics against myeloid malignancies.
a. Identification of novel therapeutic targets.
b. Characterization of previously identified therapeutic targets.
2. Immunological aspects of antibody therapeutics in myeloid malignancies.
a. Antibody-Fc receptor interactions.
b. Immune cell evasions mechanisms.
c. Antibody engineering.
3. Clinical data describing the use of antibody therapeutics for treating myeloid malignancies.
a. Clinical trials; efficacy, safety.
b. Immunogenicity.
Dr. Jaras holds patents related to the use of antibodies for cancer treatment. The other Topic Editors declare no competing interests with regards to the Research Topic theme.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
