Moreover, single dose anti-human CD45-ADC given to rhesus macaque nonhuman primates on days -6 or -10 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable FA patients.

A single dose of 3 mg/kg MGTA-45 resulted in long-term disease-free survival in all animals (median >330 days) while control groups (vehicle, isotype-ADC, or cytarabine standard of care) had median survival of 52-64 days (P < 0.005, n=5-8 mice/group).  Targeting CD45-expressing hematopoietic cells with MGTA-45, a novel anti-CD45-ADC, potently depleted HSCs and immune cells in vitro and in vivo and enabled donor cell engraftment in a nonhuman primate transplant model. MGTA-45 also significantly extended survival in a PDX model of AML refractory to standard of care. Overall, targeted conditioning using MGTA-45 could improve the risk-benefit profile of HSCT, expanding the patient population able to receive these potentially curative therapies.

By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.

In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.

Conclusion Together, we show that MPN NSC reside in a CD34+/CD38− fraction of the malignant clone and display a unique phenotype, including immune checkpoint molecules, cytokine receptors and other target antigens. Our results should support the isolation of MPN NSC and the development of NSC-eradicating therapies in MPN.

Despite being tested in highly immune-deficient mice, the naked antibody AO-176 exhibited significant single-agent in vivo anti-leukemic activity against pediatric T-lineage ALL PDXs. The significant decrease in spleen infiltration elicited by AO-176 in 3/4 PDXs suggests on-target activity consistent with the known mechanism of action of CD47 targeting agents.

Both ADC alone (p=0.0004) and ADC+anti-PD-L1 dual treatment (p=0.01) significantly decreased CD4+FoxP3+ regulatory T cells. These results provide evidence that HER2-targeted ADC + anti-PD-L1 immunotherapy-induced B cell activation and differentiation along with the modulation of T cell subsets could confer host anti-HER2 immunity.

In addition, administration of CDX alone or in combination with PD1 in humanized mice resulted in efficient elimination of the human hematopoietic compartment from the mouse bone marrow. Based on our findings, CDX shows promise for treatment of AML with concurrent conditioning for HSCT with improved specificity compared to standard of care and even displays synergy with checkpoint inhibition of PD1.