DOCSLIB.ORG

Change the Normal Expose the Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Change Expose the normal the cancer September 2021 1 Confidential Disclaimer This presentation (the “Presentation”) contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 about Vor Biopharma Inc. (“Vor” or the “Company”) that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Presentation, are forward looking statements including, but not limited to, terms such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “project,” “should,” “target,” “vision,” “will,” “would,” or other similar expressions. Such forward-looking statements in this Presentation include those regarding Vor’s plans, strategies and expectations for its preclinical and clinical programs, including the anticipated milestones and related catalysts of such programs. Vor may not actually achieve the plans, intentions, or expectations disclosed in these forward- looking statements. These forward-looking statements should not be relied upon as representing Vor’s views as of any date subsequent to the date of this Presentation. Factors that could cause actual results to differ include, but are not limited to, Vor’s dependence on its product candidates VOR33 and VCAR33, the risks inherent in biopharmaceutical product development and clinical trials, including the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation, enrollment and completion of clinical trials, whether the clinical trials will validate the safety and efficacy of VOR33 and VCAR33 in acute myeloid leukemia or other indications, and the impact of the COVID-19 pandemic on Vor’s business, operations, strategy and anticipated milestones, among others. These and other risks are described in greater detail under the caption “Risk Factors” in Vor’s reports filed with the Securities and Exchange Commission (“SEC”), and in other filings that Vor may make with the SEC in the future. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward- looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward- looking statements we make. In addition, the forward-looking statements included in this Presentation represent our views as of the date of this Presentation. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third party sources. In addition, the third party information included in this Presentation may involve a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. 2 Vor’s Vision Cure blood cancer through transformative cell engineering Hematopoietic Genome CAR-T Stem Cells Engineering Cell Therapies VOR PLATFORM 3 Changing the Thinking on Tumor Targeting Traditional Paradigm for Vor Paradigm: Reality Drug Development Engineered HSCs (eHSCs) Target Expression Cancer cell Healthy cell Problem: few unique cancer antigens, Solution: remove target expression Philosophy: target cancer so drugs kill both cancer and healthy on healthy cells so that killing is antigens to kill cancer cells cells through on-target toxicity cancer-specific 4 Myeloid Cancer Unmet Need is Large and Increasing Most Common Form of Frequent Relapse More Allogeneic Transplants Adult Acute Leukemia Post-Transplant 5000 0.8 Status at Time of Transplant Remission (MRD+) 4000 MDS 0.6 Active disease 3000 0.4 ~20,000 – AML cases diagnosed 2000 AML Remission (MRD ) annually 0.2 1000 Annual US Allogeneic HSCT US Annual Allogeneic Cumulative Incidence of Incidence Relapse Cumulative 0.0 0 2000 2005 2010 2015 0 2 4 6 8 Years Since HSCT For patients who relapse post-transplant, 2-year survival is <20% 5 The Vision: eHSC + CAR-T Treatment Systems VOR33 Mylotarg Designed by renowned CAR-T cell expert Dr. Terry Fry Treatment-resistant 1st generation HSC transplant antibody-drug conjugate • Exclusively licensed from NIH • CAR construct in multi-site Phase 1/2 pediatric NMDP-sponsored trial in R/R AML Potential advantages for healthy VOR33 VCAR33 donor cell source Treatment-resistant Allogeneic CAR-T • Tolerized to new bone marrow HSC transplant • Healthy T cell phenotype May avoid tumor escape mechanisms Multiplex-edited Multi-specific HSCs CAR-Ts May address tumor heterogeneity Multi-treatment-resistant Abound Bio collaboration HSC transplant 6 Expanding Pipeline Driven by Innovative Platform Description Preclinical Clinical Anticipated Milestones Discovery/ IND- Program Modality Indication Phase 1/2 Phase 2/3 Validation Enabling AML with Mylotarg • 1H 2022: Initial clinical data VOR33 eHSC (CD33) MDS, MPN • Development candidate selection VCAR33 Bridge-to- • 2022: Initial monotherapy CAR-T NMDP-sponsored trial* (CD33) transplant AML clinical proof-of-concept data* VOR33 / VCAR33 eHSC / • 2H 2022: IND filing following AML Treatment System CAR-T initial VOR33 and NMDP clinical data* Discovery Programs • Leveraging our proprietary Vor platform, we have identified additional surface targets such as CD123 and CLL-1 as well as multiplex genome Vor Platform engineering approaches where multiple surface targets are removed. • Additionally, we are conducting ongoing discovery efforts on undisclosed targets for non-myeloid malignancies. AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm * The VCAR33 construct is being studied in a Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (“NMDP”), and the timing of data release is dependent on the investigators conducting the trial. See appendix for more information. 7 Preclinical Validation of CD33 Deletion in HSCs 1. Homing 2. Engraftment 3. Survival Migrate to bone Repopulate the blood Fully functional Resistance to marrow system blood cells toxic therapy ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 8 VOR33: No Observed Impact on Cell Populations or Function Bone Marrow Cells B Cells Phagocytosis 80 100 100 80 80 60 Control 60 60 40 VOR33 40 40 %hCD45+ %hCD19+ 20 20 %Phagocytosis 20 0 0 0 Control VOR33 Control VOR33 +E.coli +E.coli +CytoD Myeloid Cells Cytokine Production 10 20 10,000 TNF 1,000,000 IL-6 100,000 MIP-1 ⍺ 100,000 10,000 ⍺ 8 15 1,000 10,000 6 1,000 10 100 1,000 pg/mL 100 4 100 %hCD14+ %hCD11b+ 10 2 5 10 10 0 0 0 0 0 Basal LPS R848 Basal LPS R848 Basal LPS R848 Control VOR33 Control VOR33 n=3 per group Control VOR33 9 Strongest Supportive Evidence for CD33 Dispensability: Human Genetics 65 individuals with homozygous loss-of-function mutations in CD33 gene in Genome Aggregation Database 10 VOR33: Resistance to CD33 Therapy In Vitro In Vivo 100 30 VOR33 ) 80 + 20 60 ~70-Fold (% in hCD45 40 + 10 % Live Cells 20 Control CD14 0 0 Vh Mylotarg Vh Mylotarg Mylotarg, ng/mL Control VOR33 • Engineered cells were not enriched for CD33 deletion and some cell death was expected based on residual CD33 expression • Free calicheamicin dissociated from Mylotarg may have led to non-specific cell death 11 VOR33: Streamlined Cell Manufacturing Process Hematopoietic Stem Cells Vor is Building a Fully Integrated Manufacturing Facility for eHSC and CAR-T Drug Products CAR-T Cells Overnight Material Cell Genome Overnight shipped preparation selection engineering shipped Engineered Hematopoietic Starting Material T cell Stem Cells (eHSCs) VOR33 eHSC Drug Product Apheresis Product from fraction Ready for Patient Dosing Potential Healthy Matched Donor CAR-T material VOR33: ~3-day production process; 7–10-day vein-to-vein time No new genetic material nor viral vectors No cell expansion 12 VBP101: VOR33+Mylotarg Phase 1/2a Clinical Trial VOR33 VOR33 Day 28 Anti-CD33 Transplant Decision Infusion Engraftment Therapy Transplant-eligible AML patients in Induction Consolidation Conditioning Mylotarg Treatment remission but at high Day 60 or earlier upon relapse risk of relapse Patient Journey Key Endpoints Stem Cell 1 VOR33 engraftment Screening Mobilization, VOR33 Collection ManufacturingManufacturing 2 Mylotarg protection vein-to-vein 7-10 days Donor Journey Related Unrelated 3 Relapse-free survival Back-up Marrow Clinical Trial Sites • MSKCC (NY) • Miami Cancer Inst. (FL) • Hôpital Maisonneuve-Rosemont (Montreal) • Fred Hutchinson Cancer Ctr. (WA) • CWRU/Seidman Cancer Ctr. (OH) • WashU Siteman Cancer Cntr. (MO) • Hackensack/Theurer Cancer Ctr. (NJ) • UC San Diego Cancer Ctr. (CA) 13 Potential Value Proposition and Reimbursement Pathways e ngineered for Protection Seamless Protected Curative H Integration Bone Marrow Intent Comparable engraftment Invisible and resistant to Unlock new treatments S Well-characterized,
Recommended publications
  • Uniqure N.V. Paasheuvelweg 25A 1105BP Amsterdam the Netherlands +1-339-970-7000

    Uniqure N.V. Paasheuvelweg 25A 1105BP Amsterdam the Netherlands +1-339-970-7000

    uniQure N.V. Paasheuvelweg 25a 1105BP Amsterdam The Netherlands +1-339-970-7000 NOTICE OF EXTRAORDINARY GENERAL MEETING OF SHAREHOLDERS To be held on September 14, 2017 To the Shareholders of uniQure N.V.: Notice is hereby given that an Extraordinary General Meeting of Shareholders (the “Extraordinary Meeting”) of uniQure N.V., a public company with limited liability ( naamloze vennootschap ) under the laws of the Netherlands (the “Company,” “uniQure,” and “we”), will be held on September 14, 2017, at 9:30 a.m., Central European Summer Time, at the Company’s principal executive offices located at Paasheuvelweg 25a, 1105BP Amsterdam, the Netherlands, for the following purposes: I. Opening and announcements; II. Appointment of Jeremy P. Springhorn, Ph.D. as a non-executive director (voting proposal no. 1); III. Appointment of Madhavan Balachandran as a non-executive director (voting proposal no. 2); IV Any other business that may properly come before the meeting or any adjournment of the meeting; and V. Closing of the meeting. Each person authorized to attend the Extraordinary Meeting may inspect the Agenda at the office of uniQure. Our Board of Directors (our “Board”) recommends that you vote “FOR” each of the voting proposals noted above. The record date is set at the close of business on August 17, 2017 EST and, therefore, only the Company’s shareholders of record at the close of business on August 17, 2017 EST are entitled to receive this notice (this “Notice”) and to vote at the Extraordinary Meeting and any adjournment thereof. Only shareholders who have given notice in writing to the Company by September 12, 2017 of their intention to attend the Extraordinary Meeting in person are entitled to attend the Extraordinary Meeting in person.
  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse

    Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse

    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
  • AML Serum Mir-150 Mir-155 Mir-1246 Prog

    AML Serum Mir-150 Mir-155 Mir-1246 Prog

    Supplementary Table S1. Summary of current studies on EVs as biomarkers Disease Source Cargo Role Reference AML serum TGF-β1, CD34, Prognostic [21] CD33, CD117 AML serum miR-150 Prognostic [23] miR-155 miR-1246 AML serum miR-125b Prognostic [24] AML serum miR-10b Prognostic [25] CLL serum CD19, CD37 Prognostic [27] CLL plasma S100-A9 protein Prognostic [29] CLL plasma CD52 Prognostic [30] CLL plasma miR-150, miR-155, Diagnostic [31] miR-223, miR-29 CD37, CD9, CD63 CLL plasma mc-COX2 Prognostic [33] MF plasma CD61, CD62P Prognostic [34] MM serum CD38, CD138, Prognostic [37] CD44, CD147 MM serum let-7b and miR-18a Prognostic [40] nHL /HL plasma CD20/CD30 Diagnostic/Prognostic [20] Lymphoma plasma CD20 Prognostic [43] HL plasma miR-23p Diagnostic [44] miR-127-3p miR-21-5p miR-155-5p let-7a-5p Lymphoma plasma BCL-6 Prognostic [45] c-myc 1 Supplementary Table S2. Summary of current studies on EVs: re-education of the bone marrow niche Disease EV Target Cargo Functional effects Reference origin/Source AML AML cells MSC/stromal / Downregulating of KITL, [52] cells CXCL12, IGF1; Reducing support to normal hemopoiesis AML AML cells Stromal cells miR-155 Reducing secretion of [54] miR-375 cytokines and growth factor; miR-150 Affecting retention and differentiation of HSC in the bone marrow AML/MDS AML/MDS cells MSC miR-7977 Reducing the hemopoiesis [55] supportive capacity CLL CLL cells MSC miR-202-3p Promoting migration, [32] survival and proliferation CLL Plasma Stromal cells / Production of VEGF, [26] promoting survival of B cells CLL CLL cells
  • Immunocytochemical Analysis of Human Synovial Lining Cells: Phenotypic Relation to Other Marrow Ann Rheum Dis: First Published As 10.1136/Ard.50.5.311 on 1 May 1991

    Immunocytochemical Analysis of Human Synovial Lining Cells: Phenotypic Relation to Other Marrow Ann Rheum Dis: First Published As 10.1136/Ard.50.5.311 on 1 May 1991

    Annals ofthe Rheumatic Diseases 1991; 50: 311-315 31 Immunocytochemical analysis of human synovial lining cells: phenotypic relation to other marrow Ann Rheum Dis: first published as 10.1136/ard.50.5.311 on 1 May 1991. Downloaded from derived cells N A Athanasou, J Quinn Abstract system,20 21 synovial lining cell specific The antigenic phenotype of human synovial progenitors are produced in the marrow by a lining cells in normal and hyperplastic synovial lining cell lineage that diverges at some synovium intima was determined with a panel early stage from that of monocytes and tissue of monoclonal antibodies directed against macrophages. a large number of well defined myeloid To investigate the origin and development of (macrophage/granulocyte associated) antigens. synovial lining cells further we sought to define Synovial lining cells express numerous macro- the antigenic phenotype of human synovial phage associated antigens, including CD11b lining cells and subintimal macrophages in the (CR3), CD13, CD14, CD16 (FcRIII), CD18, synovial membrane. We used a large number of CD32 (FcRII), CD45 (leucocyte common monoclonal antibodies directed against defined antigen), CD54 (ICAM-1), CD64 (FcRI), myeloid (granulocyte/macrophage associated) CD68, and CD71 (transferrin receptor). antigens for the immunohistochemical staining Few synovial lining cells expressed CD11a of human synovial lining cells and subintimal (LFA-1) and CD11c (p150,95). Subintimal macrophages in the synovial membrane. The macrophages expressed all the macrophage pattern of antigen expression by these cells not associated antigens which were present on only has implications for synovial lining cell synovial lining cells and, in addition, expressed origin and development but also for function CD15a, CD25 (interleukin-2 receptor), CD34, and interaction of these cells with other inflam- and CD35 (C3b receptor), none of which was matory cells.
  • Interim Recommendations for Use of the Moderna Mrna-1273 Vaccine Against COVID-19

    Interim Recommendations for Use of the Moderna Mrna-1273 Vaccine Against COVID-19

    Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19 Interim guidance First issued 25 January 2021 Updated 15 June 2021 Background This interim guidance has been developed on the basis of the advice issued by the Strategic Advisory Group of Experts on Immunization (SAGE) at its extraordinary meeting on 21 January 2021 (1) and updated during its extraordinary meeting on 27 May 2021(2). Declarations of interests were collected from all external contributors and assessed for any conflicts of interest. Summaries of the reported interests can be found on the SAGE meeting website and SAGE Working Group website. The guidance is based on the evidence summarised in the Background document on the Moderna mRNA-1273 vaccine against COVID-19 (3) and the background paper on COVID-19 disease and vaccines (4). Annexes which include GRADE and evidence-to-recommendations (ETR) tables have also been updated to reflect the updated recommendations. All referenced documents are available on the SAGE COVID-19 webpage: https://www.who.int/groups/strategic- advisory-group-of-experts-on-immunization/covid-19-materials. These interim recommendations refer to the mRNA-1273 vaccine, manufactured by Moderna. The vaccine is also known as COVID-19 Vaccine Moderna. In the subsequent text the vaccine will be referred to as mRNA-1273. On 30 April 2021, mRNA-1273 was granted WHO’s Emergency Use Listing (EUL). Methods SAGE applies the principles of evidence-based medicine and has set in place a thorough methodological process for issuing and updating recommendations (5). A detailed description of the methodological processes as they apply to COVID-19 vaccines can be found in the SAGE evidence framework for COVID-19 vaccines (6).
  • Moderna Vaccine Day Presentation

    Moderna Vaccine Day Presentation

    Zika Encoded VLP mRNA(s) RSV CMV + EBV SARS-CoV- RSV-ped 2 Flu hMPV/PIV3 H7N9 Encoded mRNA(s) Ribosome Protein chain(s) First Vaccines Day April 14, 2020 © 2020 M oderna Therapeutics Forward-looking statements and disclaimers This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended including, but not limited to, statements concerning; the impact of the SARS-CoV-2 pandemic on the Company’s clinical trials and operations; the timing and finalization of a dose-confirmation Phase 2 study and planning for a pivotal Phase 3 study for mRNA-1647; the status and outcome of the Phase 1 clinical trial for mRNA-1273 being conducted by NIH; the next steps and ultimate commercial plan for mRNA-1273; the size of the potential market opportunity for mRNA-1273; the size of the potential commercial market for novel vaccines produced by Moderna or others; the potential peak sales for the Company’s wholly-owned vaccines; the probability of success of the Company’s vaccines individually and as a portfolio; and the ability of the Company to accelerate the research and development timeline for any individual product or the platform as a whole. In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements.
  • The Covid–19 Pandemic and Haemoglobin Disorders

    The Covid–19 Pandemic and Haemoglobin Disorders

    THE COVID–19 PANDEMIC AND HAEMOGLOBIN DISORDERS VACCINATIONS & THERAPEUTIC DRUGS An Informational Guide from the Thalassaemia International Federation (TIF) Prepared by: Dr Androulla Eleftheriou, Executive Director, TIF Last Updated: 12 May 2020 VACCINATIONS & THERAPEUTIC DRUGS Introduction It is important to note that there are currently no FDA1 or EMA2-approved or even recommended agents for the treatment of the novel coronavirus (COVID-19), for which the World Health Organization (WHO) declared as pandemic on Wednesday 11th of March 2020. Any agent being used at this time is being administered in an experimental setting under controlled conditions. Thalassaemia International Federation (TIF) has made an effort to compile a list of studies/clinical trials for treatment and vaccines, which is by no means exhaustive as this situation is extremely labile and research in this area is dramatically intensified. New information is anticipated to be added to this guide which is prepared exclusively for TIF’s global thalassemia community. The viral genome was mapped very soon as rom early January 2020 and shared globally. In February 2020, the WHO published an overview of the potential therapeutic candidates for the treatment of COVID-19. The document outlines 76 regimens that have been proposed (as of February 17, 2020) for the treatment of patients infected with the virus. Thirty-eight of these candidates are in the preclinical state with minimal information available on their proposed mechanism, uses, doses routes, or planned trials. Sixteen of the remaining regimens contain an interferon-based product. The rest include a variety of antimicrobials, corticosteroids, convalescent plasma, and biologics. The Director-General of the WHO, Mr Tedros Adhanom, stated on the 10th of April 2020, that more than 70 countries have joined WHO’s trial to accelerate research on effective treatments and 20 Institutions and companies ‘are racing to develop a vaccine’.
  • Biopharma R&D on Treatment and Vaccines

    Biopharma R&D on Treatment and Vaccines

    Biopharma R&D on Treatment and Vaccines Coronavirus: Gilead Readies For Remdesivir Ramp Up, Questions On Profit Motive Demand Could Be High For Antiviral Executive Summary “All of that is at risk in not knowing if the drug If clinical trials prove it effective against COVID-19, works or not – and that is really not with an eye to remdesivir could potentially help millions of commercial,” she added. patients - which raises big questions about funding and access. Mercier said the company was spending more time on considering issues of access to the drug once its safety and efficacy is established – especially in regions of the world with less As vaccines will take around 12 months to developed healthcare systems. develop, companies with antiviral treatments are now been pushed to the front line in the battle Nevertheless, Gilead is contemplating a possible against coronavirus, and Gilead Sciences Inc.’s commercial future for the drug. remdesivir is currently the biggest hope of a drug to treat infected patients. “I have to be honest, commercial opportunity might come if this becomes a seasonal disease The company had big news to talk about on 2 or if stockpiling comes into play, but that is much March at the Cowen Health Care conference, as it later down the line,” concluded Mercier. had announced earlier in the day the acquisition of oncology firm Forty Seven for $4.9bn. (Also see One precedent for a big commercial hit for an “Gilead Calls Forty Seven Buyout Complementary antiviral product is Roche’s Tamiflu (oseltamivir). To Kite, Other IO Efforts” - Scrip, 2 Mar, 2020.) The drug achieved peak revenues of $3bn in 2009, largely down to stockpiling in response to that Speaking at the investor conference, Gilead’s chief year’s H1N1 flu pandemic.
  • Human Lectins, Their Carbohydrate Affinities and Where to Find Them

    Human Lectins, Their Carbohydrate Affinities and Where to Find Them

    biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body.
  • CD33-Specific Chimeric Antigen Receptor T Cells Exhibit Potent Preclinical Activity Against Human Acute Myeloid Leukemia

    CD33-Specific Chimeric Antigen Receptor T Cells Exhibit Potent Preclinical Activity Against Human Acute Myeloid Leukemia

    Leukemia (2015) 29, 1637–1647 © 2015 Macmillan Publishers Limited All rights reserved 0887-6924/15 www.nature.com/leu ORIGINAL ARTICLE CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia SS Kenderian1,2,5, M Ruella1,5, O Shestova1, M Klichinsky1, V Aikawa3, JJD Morrissette3, J Scholler1, D Song1, DL Porter1,4, M Carroll4, CH June1 and S Gill1,4 Patients with chemo-refractory acute myeloid leukemia (AML) have a dismal prognosis. Chimeric antigen receptor T (CART) cell therapy has produced exciting results in CD19+ malignancies and may overcome many of the limitations of conventional leukemia therapies. We developed CART cells to target CD33 (CART33) using the anti-CD33 single chain variable fragment used in gemtuzumab ozogamicin (clone My96) and tested the activity and toxicity of these cells. CART33 exhibited significant effector functions in vitro and resulted in eradication of leukemia and prolonged survival in AML xenografts. CART33 also resulted in human lineage cytopenias and reduction of myeloid progenitors in xenograft models of hematopoietic toxicity, suggesting that permanently expressed CD33-specific CART cells would have unacceptable toxicity. To enhance the viability of CART33 as an option for AML, we designed a transiently expressed mRNA anti-CD33 CAR. Gene transfer was carried out by electroporation into T cells and resulted in high-level expression with potent but self-limited activity against AML. Thus our preclinical studies show potent activity of CART33 and indicate that transient expression of anti-CD33 CAR by RNA modification could be used in patients to avoid long-term myelosuppression. CART33 therapy could be used alone or as part of a preparative regimen prior to allogeneic transplantation in refractory AML.
  • Multiomics of Azacitidine-Treated AML Cells Reveals Variable And

    Multiomics of Azacitidine-Treated AML Cells Reveals Variable And

    Multiomics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell-surface proteome Kevin K. Leunga, Aaron Nguyenb, Tao Shic, Lin Tangc, Xiaochun Nid, Laure Escoubetc, Kyle J. MacBethb, Jorge DiMartinob, and James A. Wellsa,1 aDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143; bEpigenetics Thematic Center of Excellence, Celgene Corporation, San Francisco, CA 94158; cDepartment of Informatics and Predictive Sciences, Celgene Corporation, San Diego, CA 92121; and dDepartment of Informatics and Predictive Sciences, Celgene Corporation, Cambridge, MA 02140 Contributed by James A. Wells, November 19, 2018 (sent for review August 23, 2018; reviewed by Rebekah Gundry, Neil L. Kelleher, and Bernd Wollscheid) Myelodysplastic syndromes (MDS) and acute myeloid leukemia of DNA methyltransferases, leading to loss of methylation in (AML) are diseases of abnormal hematopoietic differentiation newly synthesized DNA (10, 11). It was recently shown that AZA with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA treatment of cervical (12, 13) and colorectal (14) cancer cells methyltransferase inhibitor widely used to treat MDS and AML, can induce interferon responses through reactivation of endoge- yet the impact of AZA on the cell-surface proteome has not been nous retroviruses. This phenomenon, termed viral mimicry, is defined. To identify potential therapeutic targets for use in com- thought to induce antitumor effects by activating and engaging bination with AZA in AML patients, we investigated the effects the immune system. of AZA treatment on four AML cell lines representing different Although AZA treatment has demonstrated clinical benefit in stages of differentiation. The effect of AZA treatment on these AML patients, additional therapeutic options are needed (8, 9).
  • Effectiveness of Pfizer-Biontech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years — United States, January–March 2021

    Effectiveness of Pfizer-Biontech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years — United States, January–March 2021

    Morbidity and Mortality Weekly Report Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years — United States, January–March 2021 Mark W. Tenforde, MD, PhD1; Samantha M. Olson, MPH1; Wesley H. Self, MD2; H. Keipp Talbot, MD2; Christopher J. Lindsell, PhD2; Jay S. Steingrub, MD3; Nathan I. Shapiro, MD4; Adit A. Ginde, MD5; David J. Douin, MD5; Matthew E. Prekker, MD6; Samuel M. Brown, MD7; Ithan D. Peltan, MD7; Michelle N. Gong, MD8; Amira Mohamed, MD8; Akram Khan, MD9; Matthew C. Exline, MD10; D. Clark Files, MD11; Kevin W. Gibbs, MD11; William B. Stubblefield, MD2; Jonathan D. Casey, MD2; Todd W. Rice, MD2; Carlos G. Grijalva, MD2; David N. Hager, MD, PhD12; Arber Shehu, MD12; Nida Qadir, MD13; Steven Y. Chang, MD, PhD13; Jennifer G. Wilson, MD14; Manjusha Gaglani, MBBS15,16; Kempapura Murthy, MPH15; Nicole Calhoun, LMSW, MPA15; Arnold S. Monto, MD17; Emily T. Martin, PhD17; Anurag Malani, MD18; Richard K. Zimmerman, MD19; Fernanda P. Silveira, MD19; Donald B. Middleton, MD19; Yuwei Zhu, MD2; Dayna Wyatt2; Meagan Stephenson, MPH1; Adrienne Baughman2; Kelsey N. Womack, PhD2; Kimberly W. Hart2; Miwako Kobayashi, MD1; Jennifer R. Verani, MD1; Manish M. Patel, MD1; IVY Network; HAIVEN Investigators On April 28, 2021, this report was posted as an MMWR Early ≥65 years. Vaccination is a critical tool for reducing severe Release on the MMWR website (https://www.cdc.gov/mmwr). COVID-19 in groups at high risk. Adults aged ≥65 years are at increased risk for severe outcomes Randomized clinical trials of vaccines that have received an from COVID-19 and were identified as a priority group to EUA in the United States showed efficacy of 94%–95% in receive the first COVID-19 vaccines approved for use under preventing COVID-19–associated illness (4,5).§ However, an Emergency Use Authorization (EUA) in the United States hospitalization is a rare outcome among patients with (1–3).