- |||||||||| Clinical, Journal: Recent Progress in Clinical Development of Therapeutic Antibodies Targeting Glycan-Binding Proteins. (Pubmed Central) - Oct 31, 2019
The clinical investigations demonstrated benefits of treatments with one antibody-drug conjugate against CD22 being approved by the regulatory agencies. The recent progresses in clinical developments of these antibodies have provided great promises in therapeutic targeting of more glycan-binding proteins for treating multiple diseases, including inflammation, autoimmune diseases, and hematological malignancies.
- |||||||||| AMG 330 / Amgen
Journal, Myeloid-derived suppressor cells: CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells. (Pubmed Central) - Oct 28, 2019 This finding was corroborated in experiments showing that adding MDSCs into co-cultures of T- and AML-cells reduced AML-blast killing, while IDO inhibition promotes AMG 330-mediated clearance of AML-blasts. Taken together, our results suggest that AMG 330 may achieve anti-leukemic efficacy not only through T-cell-mediated cytotoxicity against AML-blasts but also against CD33 MDSCs, suggesting that it is worth exploring the predictive role of MDSCs for responsiveness towards an AMG 330-based therapy.
- |||||||||| azacitidine oral (CC-486) / Celgene, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
MODULE 4: Other Novel Agents and Strategies Under Evaluation for AML (Hilton Orlando , Orange Ballroom) - Oct 27, 2019 - Abstract #ASH2019ASH_74; Taken together, our results suggest that AMG 330 may achieve anti-leukemic efficacy not only through T-cell-mediated cytotoxicity against AML-blasts but also against CD33 MDSCs, suggesting that it is worth exploring the predictive role of MDSCs for responsiveness towards an AMG 330-based therapy. Biologic rationale for targeting CD33 in AML; meta-analysis of randomized trials of gemtuzumab ozogamicin with standard induction chemotherapy demonstrating an overall survival benefit for patients without adverse cytogenetics FDA “reapproval” and current clinical role of gemtuzumab ozogamicin Early clinical trial data with and ongoing Phase III evaluation of CC-486 as maintenance therapy for patients with AML in complete remission Early activity and safety data with novel immunotherapeutic approaches (eg, checkpoint inhibitors, chimeric antigen receptor [CAR] T-cell therapy) for AML Available data with and ongoing evaluation of other promising agents in AML
- |||||||||| Kidney Residency of VISTA-Positive Macrophages Accelerates Repair from Ischemic Injury (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2359;
CD14+ CD33+ mononuclear phagocytes of human kidney also expressed VISTA, which had similar functions to the mouse counterpart. Conclusion VISTA is upregulated in kidney macrophages in a tissue-dependent manner, which plays a repair role from ischemic injury.
- |||||||||| PHAGO - Targeting TREM2 and CD33 of phagocytes for treatment of Alzheimer’s disease () - Oct 7, 2019 - Abstract #AEC2019AEC_875;
2018). The CD33 crystal structure complexed with sialic acid derivatives has been resolved (Miles et al, 2019) to eventually support rational drug design.The PHAGO consortium is also interacting with other IMI-collaborative undertakings in order to maximally utilize synergisms throughout the European Research landscape, e.g. in bioinformatics (IMI ADAPTED), iPSC (IMI EBiSC2) and animal models of tauopathy (IMI IMPRiND).”
- |||||||||| Deciphering the tumor immune microenvironment of HPV-negative and -positive oropharyngeal tumors () - Oct 4, 2019 - Abstract #CRICIMTEATIAACR2019CRI-CIMT-EATI-AACR_114;
These CD14-CD33-CD163+ DC produce high levels of IL-12 and IL-18 and stimulate allogeneic CD4+ and CD8+ T cell proliferation with a similar capacity as the recently defined inflammatory type CD1c+ DC, and were associated with improved survival. Interestingly, in HPV-driven cervical cancer these Foxp3+Tbet+ Tregs and CD14- CD33-CD163+ DCs were also present and positively correlated with HPV16-specific T cell infiltration.
- |||||||||| Targeting the Stress Response Kinase GCN2 to Restore Immunity in the Tumor Microenvironment (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_934;
The GCN2/eIF2a pathway is activated in immune cells during amino acid deprivation, and this induces a functional suppression of the immune response. Our results demonstrate that inhibition of GCN2 is an attractive approach for relieving T cell suppression and promoting anti-tumor activity, demonstrating GCN2 as a promising therapeutic target for the treatment of cancer.
- |||||||||| AMV-564 / J&J, Affimed
AMV564, a novel bivalent, bispecific T-cell engager, targets myeloid-derived suppressor cells (Potomac Ballroom CD) - Oct 2, 2019 - Abstract #SITC2019SITC_356; Treatment with AMV564 selectively depletes MDSCs in a dose-dependent fashion both ex vivo and in patients. The ability of AMV564 to deplete MDSCs while activating T cells should lower the threshold necessary for a patient to respond to immunotherapy, and these results indicate potential for benefit in solid tumor indications where elevated MDSCs are associated with poor outcomes including inadequate response to immunotherapy.
- |||||||||| Targeting myeloid tumors by Off-the-Shelf NK cells using an NKG2C-IL15-CD33 Trispecific Killer Engager (National Harbor 10-11) - Oct 2, 2019 - Abstract #SITC2019SITC_347;
Engaging NK cells through NKG2C or genetically modified iNK cells expressing NKG2C, will be more specific than targeting through CD16, which will bind to CD16A on NK cells but also have off-target binding to CD16B on neutrophils. The NKG2C1533 TriKE is an effective way to selectively target NK cells with two applications, one in individuals with high frequencies of NKG2C+ cells and another within the iNK cell platform creating an "off-the-shelf" NK cellular therapy that is targeted, specific and efficacious where TriKE can be co-administered or in the future, secreted by the engineered iNK cell itself.
- |||||||||| Intratumoral CD163+ DC amplify the type 1 immune response of CD4+CD161+ T cells in HPV16-associated cancers and are associated with better survival (Potomac Ballroom AB) - Oct 2, 2019 - Abstract #SITC2019SITC_329;
The NKG2C1533 TriKE is an effective way to selectively target NK cells with two applications, one in individuals with high frequencies of NKG2C+ cells and another within the iNK cell platform creating an "off-the-shelf" NK cellular therapy that is targeted, specific and efficacious where TriKE can be co-administered or in the future, secreted by the engineered iNK cell itself. In conclusion, intratumoral CD163+ DC contribute to a stronger antitumor response through the production of IL-12 and IL-18 which amplifies especially the type 1 response of CD4+CD161+ T cells as these cells are more sensitive to IL-12 and IL-18 than their CD161- counterparts.
- |||||||||| Journal: New and emerging therapies for acute myeloid leukaemia. (Pubmed Central) - Oct 2, 2019
Additional novel therapies in development for AML include agents that target B cell lymphoma 2, FLT3, IDH1, the ubiquitination pathway, as well as cell therapy using engineered T cells with chimeric antigen receptors. This review provides a summary of the four newly approved therapies for AML, as well as several promising therapies currently in development.
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Use of Gemtuzumab Ozogamicin in Acute Myeloid Leukemia () - Sep 26, 2019 - Abstract #SOHO2019SOHO_279; Still, as a cautionary note, recently reported data from the randomized AMLSG 09-09 trial showed a substantial increase in higher early mortality rates when GO at a dose of 3 mg/m2 was added to intensive induction chemotherapy (idarubicin, cytarabine, etoposide, and all-trans retinoic acid) for patients ≥60 years of age with NPM1-mutated AML, highlighting the fact that additional toxicity can occur when GO is added to multiagent chemotherapy, even at low doses...At the same time, multi-tyrosine kinase inhibitor midostaurin and higher doses of daunorubicin have also shown to improve outcomes in randomized trials in FLT3-mutated AML...Addressing these (and other) open questions, ideally as part of controlled clinical trials, will help optimize clinical use of GO and maximize benefits with this antibody-drug conjugate.Acknowledgements R.B.W. is a Leukemia & Lymphoma Society Scholar in Clinical Research.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
Establishment and application of a series of systemic bioluminescent hematologic cell line derived xenograft models (Board 9: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_41; Our data show that lenalidomide treatment leads to statistically significant anti-tumor response in MM.1S-Luc; while rituximab led to lower tumor burden in Raji-Luc, with no significant benefit on survival. We have generated a series of systemic bioluminescent cell line xenograft models compatible with optical imaging to facilitate the drug discovery work for hematologic malignancies.
- |||||||||| Journal, PD(L)-1 Biomarker, IO Biomarker: Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells. (Pubmed Central) - Sep 14, 2019
T cell expression of Siglec-9 in NSCLC patients correlated with a reduced survival, and Siglec-9 polymorphisms showed associations with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as new potential target to improve T cell activation for immunotherapy.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO Biomarker: Microglial Drug Targets in AD: Opportunities and Challenges in Drug Discovery and Development. (Pubmed Central) - Sep 13, 2019
This makes CNS drug discovery, even with well-validated targets, challenging. In this article, we will illustrate the special challenges of AD drug discovery by discussing the viability/practicality of possible microglia drug targets including cluster of differentiation 33 (CD33), K3.1, kynurenines, ionotropic P2 receptor 7 (P2X7), programmed death-1 (PD-1), Toll-like receptors (TLRs), and triggering receptor expressed in myeloid cells 2 (TREM2).
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Clinical, Journal: Clinical Significance of ABCB1 in Acute Myeloid Leukemia: A Comprehensive Study. (Pubmed Central) - Sep 11, 2019 We showed prognostic importance of ABCB1 gene expression, protein expression, and activity. Furthermore, ABCB1 was not directly linked to drug resistance, ABCB1 inhibition did not improve outcome of high ABCB1 AML patients and thus high ABCB1 may represent a passenger characteristic of high-risk AML.
- |||||||||| Journal: Alzheimer's Disease Susceptibility Genes in Malignant Breast Tumors. (Pubmed Central) - Aug 29, 2019
It would be important to know which APOE allele(s) were co-occurrent with CD33 and CD2AP and whether co-occurrence in the tumor predicted increased risk of AD. This information could help in identification of specific risk factors for breast cancer-related cognitive decline in older women, which has important implications for oncology care.
- |||||||||| Clinical, Journal, Myeloid-derived suppressor cells: Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer. (Pubmed Central) - Aug 15, 2019
Antibodies for checkpoint inhibition and microenvironment targeting in AML were excluded from this review. Tumor-infiltrating MDSCs, Tregs, IDO expression and IDO expression in MDSCs were correlated with clinicopathological features, NCT response, and prognosis of breast cancer patients, suggesting that they might be potential markers for clinical outcomes of NCT and help clinical decision-making for improved therapies for breast cancer.
- |||||||||| Journal: Single cell analysis of clonal architecture in acute myeloid leukaemia. (Pubmed Central) - Aug 15, 2019
However, the dominant regenerating sub-clone in 9/10 cases was NPM1 and this sub-clone was either dominant or minor in the diagnostic sample from which it was derived. This study provides further evidence, at the single cell level, for genetic variegation in sub-clones and stem cells in acute leukaemia and demonstrates both a preferential order of mutation accrual and parallel evolution of sub-clones.
- |||||||||| Biomarker, Clinical, Review, Journal, Heterogeneity: Acute Myeloid Leukemia Stem Cell Heterogeneity and Its Clinical Relevance. (Pubmed Central) - Aug 15, 2019
The strong clinical correlations suggest that the most immature phenotype detectable within a patient's AML might serve as a biomarker for "clinically relevant" LSCs. The minimal residual disease state during first remission may be the optimal setting to study novel LSC-targeted therapies, since they may have limited activity against the bulk leukemia and will be utilized at lowest tumor burden as well as least tumor heterogeneity.
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