Dataset Information

CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk Adult MDS Patients.

ABSTRACT: There is an urgent need to identify effective strategies to prevent leukemic transformation and induce sustained deep remissions in adult high-risk myelodysplastic syndrome (MDS) patients. This article discusses the clinical impact potential of bispecific antibodies (BiAB) capable of redirecting host T-cell cytotoxicity in an MHC-independent manner to malignant clones as well as immunosuppressive myeloid-derived suppressor cells (MDSC) as a new class of anti-MDS drug candidates. T-cell engaging BiAB targeting the CD123 antigen may help delay disease progression in high-risk adult MDS and potentially reduce the risk of transformation to secondary AML.

SUBMITTER: Uckun FM

PROVIDER: S-EPMC9261311 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk Adult MDS Patients.

Uckun Fatih M FM Watts Justin J

Frontiers in aging 20210927

There is an urgent need to identify effective strategies to prevent leukemic transformation and induce sustained deep remissions in adult high-risk myelodysplastic syndrome (MDS) patients. This article discusses the clinical impact potential of bispecific antibodies (BiAB) capable of redirecting host T-cell cytotoxicity in an MHC-independent manner to malignant clones as well as immunosuppressive myeloid-derived suppressor cells (MDSC) as a new class of anti-MDS drug candidates. T-cell engaging ...[more]

PMID: 35822053

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Project description:BackgroundMyeloid-derived suppressor cells (MDSCs) are potent suppressors of immune function and may play a key role in the development and progression of metastatic cancers. Aerobic exercise has been shown to have anticancer effects, yet the mechanisms behind this protection are largely unknown. Therefore, we examined the effects of physical activity on MDSC accumulation and function.MethodsFemale BALB/c mice were assigned to one of two primary groups: sedentary tumor (SED+TUM) or wheel run tumor (WR+TUM). After 6 weeks of voluntary wheel running, all animals were randomly subdivided into 4 different timepoint groups; 16, 20, 24, and 28 days post-tumor injection. All mice were inoculated with 4T1 mammary carcinoma cells in the mammary fat pad and WR groups continued to run for the specified time post-injection. Spleen, blood, and tumor samples were analyzed using flow cytometry to assess proportions of MDSCs.ResultsCells expressing MDSC biomarkers were detected in the spleen, blood, and tumor beginning at d16. However, since there was no evidence of immunosuppressive function until d28, we refer to them as immature myeloid cells (IMCs). Compared to SED+TUM, levels of IMCs in the spleen were significantly lower (p < 0.05) in WR+TUM at day 16 (33.0 ± 5.2%; 23.1 ± 10.2% of total cells, respectively) and day 20 (33.9 ± 8.1%; 24.3 ± 5.1% of total cells, respectively). Additionally, there were fewer circulating IMCs in WR+TUM at day 16 and MDSC levels were significantly lower (p < 0.05) in the tumor at day 28 in WR+TUM. Additionally, a non-significant 62% and 26% reduction in metastatic lung nodules was observed at days 24 and 28, respectively. At day 28, MDSCs harvested from SED+TUM significantly suppressed CD3+CD4+ T cell proliferation (3.2 ± 1.3 proliferation index) while proliferation in WR+TUM MDSC co-cultures (5.1 ± 1.7 proliferation index) was not different from controls.ConclusionsThese findings suggest that physical activity may delay the accumulation of immunosuppressive MDSCs providing a broader window of opportunity for interventions with immunotherapies.

Dataset Information

CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk Adult MDS Patients.

Publications

CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk Adult MDS Patients.

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