Genetically Engineered T Cells Killing One Cancer Cell at a Time by Taylor Dunn https://padlet.com/tedunn91/wq93pjew9dlm Kymriah (tisgenlecleucel) - CD19 CAR-T Therapy en-us 2019-09-21 08:39:49 UTC 2019-09-27 12:37:05 UTC hello@padlet.com Source Details: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387523162 Title: Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Journal: New England Journal of Medicine:
Authors: Shannon L. Maude, M.D., Ph.D., Theodore W. Laetsch, M.D., Jochen Buechner, M.D., Ph.D., Susana Rives, M.D., Ph.D., Michael Boyer, M.D., Henrique Bittencourt, M.D., Ph.D., Peter Bader, M.D., Michael R. Verneris, M.D., Heather E. Stefanski, M.D., Ph.D., Gary D. Myers, M.D., Muna Qayed, M.D., Barbara De Moerloose, M.D., Ph.D., Hidefumi Hiramatsu, M.D., Ph.D., Krysta Schlis, M.D., Kara L. Davis, D.O., Paul L. Martin, M.D., Ph.D., Eneida R. Nemecek, M.D., Gregory A. Yanik, M.D., Christina Peters, M.D., Andre Baruchel, M.D., Nicolas Boissel, M.D., Ph.D., Francoise Mechinaud, M.D., Adriana Balduzzi, M.D., Joerg Krueger, M.D., Carl H. June, M.D., Bruce L. Levine, Ph.D., Patricia Wood, M.D., Ph.D., Tetiana Taran, M.D., Mimi Leung, M.P.H., Karen T. Mueller, Pharm.D., Yiyun Zhang, Ph.D., Kapildeb Sen, Ph.D., David Lebwohl, M.D., Michael A. Pulsipher, M.D., Stephan A. Grupp, M.D., Ph.D.
Associated Affiliations: From the Departments of Pediatrics (S.L.M., S.A.G.) and Pathology and Laboratory Medicine (C.H.J., B.L.L.), Perelman School of Medicine, and Abramson Cancer Center (C.H.J., B.L.L.), University of Pennsylvania, and the Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children’s Hospital of Philadelphia (S.L.M., S.A.G.) — all in Philadelphia; the Department of Pediatrics and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, and the Pauline Allen Gill Center for Cancer and Blood Disorders, Children’s Health, Dallas (T.W.L.); the Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo (J.B.); the Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu Barcelona, Barcelona (S.R.); the Department of Pediatrics and Internal Medicine, University of Utah, Salt Lake City (M.B.); the Department of Pediatrics, Faculty of Medicine, University of Montreal, and the Hematology Oncology Division and Charles-Bruneau Cancer Center, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal (H.B.), and the Division of Haematology/Oncology/Bone Marrow Transplantation, Hospital for Sick Children, Toronto (J.K.) — all in Canada; the Division of Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany (P.B.); the Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis (M.R.V., H.E.S.); Children’s Mercy Hospital and Clinics, Kansas City, MO (G.D.M.); Aflac Cancer and Blood Disorders Center, Emory University, Atlanta (M.Q.); the Department of Pediatric Hematology–Oncology and Stem Cell Transplantation, Ghent University Hospital, and the Cancer Research Institute Ghent (CRIG), Ghent, Belgium (B.D.M.); the Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto, Japan (H.H.); the Department of Pediatrics, Stanford University School of Medicine, Stanford (K. Schlis, K.L.D.), and the Division of Hematology, Oncology, Blood and Marrow Transplant, Children’s Hospital Los Angeles, USC Keck School of Medicine, Los Angeles (M.A.P.) — all in California; the Division of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, NC (P.L.M.); Oregon Health and Science University, Portland (E.R.N.); C.S. Mott Children’s Hospital, Ann Arbor, MI (G.A.Y.); the Stem Cell Transplantation Unit, St. Anna Children’s Hospital, Vienna (C.P.); University Hospital Robert Debré and University Paris Diderot (A. Baruchel), and Saint-Louis Hospital and University Paris Diderot (N.B.), Paris; the Royal Children’s Hospital, Melbourne, VIC, Australia (F.M.); Clinica Pediatrica Universita degli Studi di Milano Bicocca, Monza, Italy (A. Balduzzi); and Novartis Pharmaceuticals (P.W., T.T., M.L., Y.Z., K. Sen, D.L.) and Novartis Institutes for Biomedical Research (K.T.M.) — both in East Hanover, NJ.]]> 2019-09-21 08:44:06 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387523162 Date Published: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387523938 February 1, 2018

]]> 2019-09-21 08:50:24 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387523938 Summary of Kymriah: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524028 Kymriah (tisagenlecleucel), a CD19+ chimeric antigen receptor (CAR) T therapy, is used in pediatric and young adult patients.  CAR-T therapy is the latest immunological technology currently being used for relapsed and/or refractory B cell lymphoblastic leukemia (B-ALL).  CAR-T therapy works by removing T cells from the patient’s body and genetically engineering them with chimeric antigen receptors (CARs) to fight the cancer by targeting specific antigens (i.e. CD19) on the cancer cells.

]]> 2019-09-21 08:51:26 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524028 Pros for Kymriah: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524360
  • Saves lives.  Excellent results for patients who have poor prognosis and have failed multiple treatment modalities. 
  • Minimal hospital stay.  Some centers allow outpatient infusions, but most require up to a two week stay. 
  • Easy procedure for the patient. T cells are removed from the body, genetically engineered over a period of a month, patients then receive five days of lymphodepleting chemotherapy in the outpatient clinic, and lastly an infusion that takes less than 30 minutes.
    • ]]>     2019-09-21 08:54:23 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524360     Cons for Kymriah: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524555
  • Expensive.  Kymriah costs approximately 1/2 million dollars for a single infusion.
  • Time consuming to produce.  It takes approximately four weeks to produce from the time of T cell collection.
  • Life threatening toxicities (i.e. cytokine release syndrome (CRS) and neurotoxicities)
    • ]]>     2019-09-21 08:56:12 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524555     Opinion with Rationale: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524782 It is my opinion that immunotherapy is a major breakthrough in cancer treatment.  Immunotherapy offers alternative treatments to standard chemotherapy with better outcomes and shorter treatment times. Immunotherapy is a step closer to finding a cure for cancer.   Specifically, Kymriah offers an additional treatment option for patients with relapsed and/or refractory B cell lymphoblastic leukemia (B-ALL) who have been told they do not have any more viable treatment options and should go home on hospice.  Although Kymriah has produced excellent results, it is important to consider the serious life threatening toxicities that are associated with this treatment option. 

    ]]>     2019-09-21 08:57:56 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387524782     Team (Strengths) tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387525699 1. Alice (Achiever)
    I chose Alice for her strong work ethic and her dedication to working hard.  No task is too difficult for her to complete and she inspires the whole team to be more like her.

    2. Angelica (Analytical)
    I choose Angelica because she is the "brain" of the team always looking for the answers to problems.  It is not enough for her to simply know the answer, she has to know "why."  She is logical and loves to work with figures.  

    3. Abraham (Arranger)
    I chose Abraham because he is an adept organizer and helps to keep the team organized.  He will manage the resources and make sure the team is as efficient as possible.

    4. Chelsea (Command)
    I choose Chelsea because she is an excellent team leader as she has no problem taking control of a situation and is experienced at making the difficult decisions in a timely manner.

    5. William (Woo)
    I chose William because he is people oriented and will have no problems building up our team and networking with other teams.]]>     2019-09-21 09:04:02 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387525699     First Pediatric CAR-T Therapy Patient Story tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387533818 CAR-T journey from the perspective of the parents of a B-ALL patient who had CD19 CAR-T performed back in the early stages of the trial in 2012]]> 2019-09-21 10:03:58 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387533818 What is CAR-T? tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387534748 2019-09-21 10:10:03 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387534748 References: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387534910 Maude, S.M., Laetsch, T.W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H …Grupp, S. (2018). Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. The New England Journal of Medicine 378, 439-448. DOI: 10.1056/NEJMoa1709866

    [MD Anderson Cancer Center]. (2019, Jan. 14). CAR-T cell therapy for cancer therapy: How it works? [Video File]. Retrieved from https://www.youtube.com/watch?v=UZpHu0gl6LU.

    [Novartis]. (2017, Dec. 1). Manufacturing CAR-T cell therapies: The Novartis approach. [Video File]. Retrieved from https://www.youtube.com/watch?v=Cmft6Sg8X3o&t=59s.

    [The Children's Hospital of Philadelphia]. (2012, Dec 9). Emily Whitehead first child in trial of T cell therapy for acute lymphoblastic leukemia. [Video File]. Retrieved from https://www.youtube.com/watch?v=pTQuZ2hWa-0
    ]]>     2019-09-21 10:11:23 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387534910     How CAR-T Cells are Engineered tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387541194 2019-09-21 10:55:32 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387541194 Link: tedunn91 https://padlet.com/tedunn91/wq93pjew9dlm/wish/387542092 https://www.nejm.org/doi/full/10.1056/NEJMoa1709866]]> 2019-09-21 11:01:17 UTC https://padlet.com/tedunn91/wq93pjew9dlm/wish/387542092