DOCSLIB.ORG

Axicabtagene Ciloleucel, a First-In-Class CAR T Cell Therapy for Aggressive NHL

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Leukemia & Lymphoma ISSN: 1042-8194 (Print) 1029-2403 (Online) Journal homepage: http://www.tandfonline.com/loi/ilal20 Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL Zachary J. Roberts, Marc Better, Adrian Bot, Margo R. Roberts & Antoni Ribas To cite this article: Zachary J. Roberts, Marc Better, Adrian Bot, Margo R. Roberts & Antoni Ribas (2017): Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL, Leukemia & Lymphoma, DOI: 10.1080/10428194.2017.1387905 To link to this article: http://dx.doi.org/10.1080/10428194.2017.1387905 © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group View supplementary material Published online: 23 Oct 2017. Submit your article to this journal Article views: 699 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ilal20 Download by: [UCLA Library] Date: 07 November 2017, At: 12:06 LEUKEMIA & LYMPHOMA, 2017 https://doi.org/10.1080/10428194.2017.1387905 REVIEW Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL Zachary J. Robertsa, Marc Bettera, Adrian Bota, Margo R. Robertsa and Antoni Ribasb aKite Pharma, Santa Monica, CA, USA; bDepartment of Medicine, University of California at Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA ABSTRACT ARTICLE HISTORY The development of clinically functional chimeric antigen receptor (CAR) T cell therapy is the cul- Received 2 June 2017 mination of multiple advances over the last three decades. Axicabtagene ciloleucel (formerly Revised 18 September 2017 KTE-C19) is an anti-CD19 CAR T cell therapy in development for patients with refractory diffuse Accepted 26 September 2017 large B cell lymphoma (DLBCL), including transformed follicular lymphoma (TFL) and primary KEYWORDS mediastinal B cell lymphoma (PMBCL). Axicabtagene ciloleucel is manufactured from patients’ CAR T cells; axicabtagene own peripheral blood mononuclear cells (PBMC) during which T cells are engineered to express ciloleucel; adoptive cell a CAR that redirects them to recognize CD19-expressing cells. Clinical trials have demonstrated transfer therapy; refractory the feasibility of manufacturing axicabtagene ciloleucel in a centralized facility for use in multi- DLBCL; immunotherapy; center clinical trials and have demonstrated potent antitumor activity in patients with refractory KTE-C19 DLBCL. Main acute toxicities are cytokine release syndrome and neurologic events. Axicabtagene ciloleucel holds promise for the treatment of patients with CD19-positive malignancies, including refractory DLBCL. Introduction typically an antibody-derived single chain variable fragment (scFv) that recognizes a tumor cell surface Rationale for and description of axicabtagene protein. The scFv is linked to intracellular signaling ciloleucel components derived from T lymphocytes, including The immune system is the body’s main defense the key intracellular signaling domain of the TCR CD3f against infection and has been shown to harbor the subunit [3]. Although essential for T cell activation, sig- potential to recognize and kill cancer cells [1]. T cells naling via CD3f is not sufficient for optimal T cell func- have emerged as central players in the immune tion. Therefore, current CARs also include the response to cancer [2]. Upon engagement of tumor intracellular signaling domain of a costimulatory recep- cells by T cells expressing tumor antigen-specific T cell tor, such as CD28 or 4-1BB, which provides additional receptors (TCRs), the T cells are activated, undergo clo- signals to optimize performance (Figure 1(B))[4,5]. nal proliferation to broaden the attack, and release CARs redirect T cells to target tumor cells in a major cytokines that can enhance antitumor activity, ultim- Downloaded by [UCLA Library] at 12:06 07 November 2017 histocompatibility complex-independent fashion, ately leading to the lysis of tumor cells. However, the ideally sparing normal cells, but at a minimum limiting immune system’s ability to eradicate cancer cells is on-target/off-tumor activity to nonessential tissues, limited by several obstacles, including insufficient depending on the antigen target. CARs are typically numbers of T cells specific to tumor-specific antigens, introduced to patients’ blood-derived T cells ex vivo a series of immune checkpoints that limit full T cell via a viral vector system. CAR T cells are then activation against cancer, and the immune suppressive expanded and administered back to patients who tumor microenvironment (Figure 1(A)). Chimeric anti- have been conditioned with a lymphodepleting gen receptor (CAR) T cell therapy may overcome some chemotherapy regimen that primes the patient for of the main limitations of the endogenous immune optimal CAR T cell in vivo expansion and antitumor system and of other cancer immunotherapies, provid- activity [6–8]. ing a new avenue to treat cancer. CARs are synthetic The development of axicabtagene ciloleucel origi- immunoreceptors whose extracellular domain is nated from earlier preclinical work conducted by CONTACT Antoni Ribas [email protected] Department of Medicine, University of California Los Angeles Jonsson Comprehensive Cancer Center, 11-934 Factor Bldg., 10833 Le Conte Avenue, Los Angeles 90095, CA, USA ß 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by- nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. 2 Z. J. ROBERTS ET AL. (A) 1 Limited number of tumor-specificecific T ccellsells Manufacture large numbers of tumor-specific T cells by CAR transduction and ex vivo expansion of autologous blood lymphocytes T cell Tumor Administer preconditioning treatment to optimize post-infusion expansion 2 Suboptimal immune cell activation and function Incorporate requisite immune-signaling domains into CAR constructs to achieve optimal T cell activity (B) Tumor Cancer cell Target antigen T cell Target binding domain Hinge Costimulatory domain • Cytolytic activity • Cytokine release • Proliferation Essential activating domain CAR-engineered T cell Figure 1. Key hurdles of antitumor immunity in B cell malignancies and how CAR technology may solve them (A), and schematic representation of a CAR (B). James Kochenderfer and Steven A. Rosenberg at the studies laid the groundwork for the first clinical report Downloaded by [UCLA Library] at 12:06 07 November 2017 Surgery Branch of the National Cancer Institute (NCI, to describe successful anti-CD19 CAR T cell therapy Bethesda, MD). The CD19-specific CAR of axicabtagene [11]. ciloleucel comprises an extracellular scFv specific for Based on the early CD19 CAR experience from the CD19 and the signaling domains of CD3f and CD28, NCI, axicabtagene ciloleucel has been generated using and was first described by Kochenderfer and col- a modified manufacturing process optimized for multi- leagues in 2009 [9]. That study demonstrated that pri- center clinical trials in aggressive non-Hodgkin lymph- mary human T cells expressing this anti-CD19 CAR oma (NHL) and other indications and for potential could produce cytokines specifically in response to future commercial applications. CD19 þ target cells and efficiently kill primary chronic lymphocytic leukemia (CLL) cells in vitro. In a later Epidemiology and treatment of aggressive B cell study, a CAR of similar design, but specific for murine lymphomas CD19 and bearing intracellular signaling domains of murine origin, was evaluated in an immune competent NHL is the seventh most common cancer in the syngeneic mouse model of lymphoma [10]. Potent United States, with an estimated 73,000 new cases in antilymphoma activity of anti-CD19 CAR T cells was 2016 [12] and several subtypes. The most prevalent observed together with the expected on-target/off- subtype of NHL is diffuse large B cell lymphoma tumor effect of normal B-cell aplasia. These preclinical (DLBCL), an aggressive disease that accounts for AXICABTAGENE CILOLEUCEL FOR LYMPHOMA 3 30–40% of NHL cases [13]. Transformed follicular 26% and a median OS of 6.3 months in patients with lymphoma (TFL) and primary mediastinal B cell lymph- refractory DLBCL [21]. This uniformly poor outcome oma (PMBCL) are rarer types of NHL [14,15]. TFL is an represents a significant unmet medical need, and aggressive form of the generally indolent follicular patients in this clinical predicament are in need of lymphoma (FL) that develops in 2–3% of FL cases per novel and efficacious treatment approaches. It is in year [16]. Although the median overall survival (OS) of patients with refractory aggressive NHL that axicabta- FL is 15 to >20 years [17,18], the median OS of TFL is gene ciloleucel is being investigated in the ZUMA-1 poor, ranging from 2.5 months to 2.5 years [14]. clinical trial. PMBCL constitutes 2–4% of NHL cases [15] and is also associated with poor outcomes [15,19]. Manufacturing axicabtagene ciloleucel First-line treatment for patients with DLBCL, PMBCL, or TFL generally consists of combination therapy with CAR T cell production processes at academic centers rituximab and chemotherapy [13,19,20]. Most new conducting single-center
Recommended publications
  • Chimeric Antigen Receptor T-Cell Therapy – Clinical Guidelines

    Chimeric Antigen Receptor T-Cell Therapy – Clinical Guidelines

    Chimeric Antigen Receptor T-cell Therapy Clinical Guideline Effective July 13, 2021 THIS DOCUMENT IS PROPRIETARY AND CONFIDENTIAL TO OPTUM® Unauthorized use or copying without written consent is strictly prohibited. Printed copies are for reference only. Table of Contents Table of Contents Introduction .................................................................................................................................... 3 FDA-approved Agents ................................................................................................................... 3 Universal Minimum Eligibility Requirements .............................................................................. 4 Indication ........................................................................................................................................ 5 Multiple Myeloma ................................................................................................................ 5 Diffuse Large B-cell Lymphoma .......................................................................................... 7 Follicular Lymphoma ......................................................................................................... 13 Mantle Cell Lymphoma ..................................................................................................... 15 Acute Lymphoblastic Leukemia (ALL) .............................................................................. 17 Universal Contraindications ......................................................................................................
  • Axicabtagene Ciloleucel (Yescarta®)

    Axicabtagene Ciloleucel (Yescarta®)

    Policy Medical Policy Manual Approved Revision: Do Not Implement until 8/31/21 Axicabtagene Ciloleucel (Yescarta®) NDC CODE(S) 71287-0119-XX YESCARTA PLASTIC BAG, INJECTION (KITE PHARMA, IN) DESCRIPTION Axicabtagene ciloleucel is a CD19-directed genetically modified autologous T cell immunotherapy. To prepare the product an individual’s own T cells are harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains. The anti-CD19 CAR T cells are expanded and infused back into the individual. Axicabtagene ciloleucel binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with CD19-expressing target cells, the CD28 and CD3-zeta co- stimulatory domains activate downstream signaling cascades that lead to T-cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19-expressing cells. POLICY Axicabtagene ciloleucel for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.) o Large B-cell Lymphoma o Follicular Lymphoma Axicabtagene ciloleucel for the treatment of other conditions/diseases is considered investigational. MEDICAL APPROPRIATENESS INITIAL APPROVAL CRITERIA Submission of medical records related
  • Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy

    Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy

    cells Review Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy Jan A. Rath and Caroline Arber * Department of oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, 1015 Lausanne, Switzerland * Correspondence: [email protected] Received: 18 May 2020; Accepted: 16 June 2020; Published: 18 June 2020 Abstract: T cell receptor (TCR)-based adoptive T cell therapies (ACT) hold great promise for the treatment of cancer, as TCRs can cover a broad range of target antigens. Here we summarize basic, translational and clinical results that provide insight into the challenges and opportunities of TCR-based ACT. We review the characteristics of target antigens and conventional αβ-TCRs, and provide a summary of published clinical trials with TCR-transgenic T cell therapies. We discuss how synthetic biology and innovative engineering strategies are poised to provide solutions for overcoming current limitations, that include functional avidity, MHC restriction, and most importantly, the tumor microenvironment. We also highlight the impact of precision genome editing on the next iteration of TCR-transgenic T cell therapies, and the discovery of novel immune engineering targets. We are convinced that some of these innovations will enable the field to move TCR gene therapy to the next level. Keywords: adoptive T cell therapy; transgenic TCR; engineered T cells; avidity; chimeric receptors; chimeric antigen receptor; cancer immunotherapy; CRISPR; gene editing; tumor microenvironment 1. Introduction Adoptive T cell therapy (ACT) with T cells expressing native or transgenic αβ-T cell receptors (TCRs) is a promising treatment for cancer, as TCRs cover a wide range of potential target antigens [1].
  • Yescarta™ (Axicabtagene Ciloleucel) – New Orphan Drug Approval

    Yescarta™ (Axicabtagene Ciloleucel) – New Orphan Drug Approval

    Yescarta™ (axicabtagene ciloleucel) – New orphan drug approval • On October 18, 2017, Kite Pharma, a Gilead company, announced the FDA approval of Yescarta (axicabtagene ciloleucel), for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. — Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. • DLBCL is the most common type of non-Hodgkin lymphoma (NHL) in adults. Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and DLBCL represents approximately one in three newly diagnosed cases. — An estimated 7,500 Americans with refractory DLBCL are eligible for chimeric antigen receptor (CAR) T-cell therapy. — With current standard of care, patients with refractory large B-cell lymphoma have a median overall survival of approximately 6 months, with only 7% attaining a complete remission (CR). — In addition, patients with large B-cell lymphoma in second or later lines of therapy have poor outcomes and greater unmet need, since nearly half of them either do not respond or relapse shortly after transplant. • Yescarta is a genetically-modified autologous T-cell immunotherapy. Each dose of Yescarta is a customized treatment created using an individual patient’s own T-cells, a type of white blood cell known as a lymphocyte. The patient’s T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a CAR that directs the T-cell to target and kill certain cancer cells that have a specific antigen (CD19) on the surface.
  • Decision Memo for Chimeric Antigen Receptor (CAR) T-Cell Therapy for Cancers (CAG-00451N)

    Decision Memo for Chimeric Antigen Receptor (CAR) T-Cell Therapy for Cancers (CAG-00451N)

    Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N) Links in PDF documents are not guaranteed to work. To follow a web link, please use the MCD Website. Decision Summary A. The Centers for Medicare & Medicaid Services (CMS) covers autologous treatment for cancer with T-cells expressing at least one chimeric antigen receptor (CAR) when administered at healthcare facilities enrolled in the FDA risk evaluation and mitigation strategies (REMS) and used for a medically accepted indication as defined at Social Security Act section 1861(t)(2) i.e., is used for either an FDA-approved indication (according to the FDA-approved label for that product), or for other uses when the product has been FDA-approved and the use is supported in one or more CMS-approved compendia. B. The use of non-FDA-approved autologous T-cells expressing at least one CAR is non-covered. Autologous treatment for cancer with T-cells expressing at least one CAR is non-covered when the requirements in Section A are not met. C. This policy continues coverage for routine costs in clinical trials that use CAR T-cell therapy as an investigational agent that meet the requirements listed in NCD 310.1. See Appendix B for the language representative of Medicare's national coverage determination (NCD) for implementation purposes only. Decision Memo TO: Administrative File: CAG-00451N FROM: Tamara Syrek Jensen, JD Director, Coverage and Analysis Group Joseph Chin, MD, MS Deputy Director, Coverage and Analysis Group Lori M. Ashby, MA Director, Division of Policy and Evidence Review Rosemarie Hakim, PhD Acting Director, Evidence Development Division Lori A.
  • Feasibility of Telomerase-Specific Adoptive T-Cell Therapy for B-Cell Chronic Lymphocytic Leukemia and Solid Malignancies

    Feasibility of Telomerase-Specific Adoptive T-Cell Therapy for B-Cell Chronic Lymphocytic Leukemia and Solid Malignancies

    Cancer Microenvironment and Immunology Research Feasibility of Telomerase-Specific Adoptive T-cell Therapy for B-cell Chronic Lymphocytic Leukemia and Solid Malignancies Sara Sandri1, Sara Bobisse2, Kelly Moxley3, Alessia Lamolinara4, Francesco De Sanctis1, Federico Boschi5, Andrea Sbarbati6, Giulio Fracasso1, Giovanna Ferrarini1, Rudi W. Hendriks7, Chiara Cavallini8, Maria Teresa Scupoli8,9, Silvia Sartoris1, Manuela Iezzi4, Michael I. Nishimura3, Vincenzo Bronte1, and Stefano Ugel1 Abstract Telomerase (TERT) is overexpressed in 80% to 90% of primary Using several relevant humanized mouse models, we demon- tumors and contributes to sustaining the transformed phenotype. strate that TCR-transduced T cells were able to control human B- The identification of several TERT epitopes in tumor cells has CLL progression in vivo and limited tumor growth in several elevated the status of TERT as a potential universal target for human, solid transplantable cancers. TERT-based adoptive selective and broad adoptive immunotherapy. TERT-specific cyto- immunotherapy selectively eliminated tumor cells, failed to trig- toxic T lymphocytes (CTL) have been detected in the peripheral ger a self–MHC-restricted fratricide of T cells, and was associated blood of B-cell chronic lymphocytic leukemia (B-CLL) patients, with toxicity against mature granulocytes, but not toward human but display low functional avidity, which limits their clinical hematopoietic progenitors in humanized immune reconstituted utility in adoptive cell transfer approaches. To overcome this mice. These data support the feasibility of TERT-based adoptive key obstacle hindering effective immunotherapy, we isolated an immunotherapy in clinical oncology, highlighting, for the first HLA-A2–restricted T-cell receptor (TCR) with high avidity for time, the possibility of utilizing a high-avidity TCR specific for à human TERT from vaccinated HLA-A 0201 transgenic mice.
  • Cancer Immunotherapy Comes of Age and Looks for Maturity ✉ Amanda Finck1, Saar I

    Cancer Immunotherapy Comes of Age and Looks for Maturity ✉ Amanda Finck1, Saar I

    COMMENT https://doi.org/10.1038/s41467-020-17140-5 OPEN Cancer immunotherapy comes of age and looks for maturity ✉ Amanda Finck1, Saar I. Gill1 & Carl H. June 1,2 As Nature Communications celebrates a 10-year anniversary, the field has witnessed the transition of cancer immunotherapy from a pipe dream to an established powerful cancer treatment modality. Here we discuss the opportu- 1234567890():,; nities and challenges for the future. Improving the natural immune system through immune checkpoint blockade interference Advances in the understanding of basic immunology have ushered in two major approaches for cancer therapy over the past 10 years. The first is checkpoint therapy to augment the function of the natural immune system. The second uses the emerging discipline of synthetic biology and the tools of molecular biology and genome engineering to create new forms of biological structures, engineered viruses and cells with enhanced functionalities (Fig. 1). Trastuzumab, the monoclonal antibody targeting HER2, was the first recombinant antibody to be commercially approved, in 1997. However, over the past 10 years, a paradigm shift in cancer therapy occurred with the addition of inhibitors of the immune checkpoint blockade (ICB), CTLA-4 and PD-1, to the clinics. The first to be approved was the anti-CTLA-4 inhibitor ipilimumab for metastatic melanoma in 2011. More than a dozen types of cancer are now treated with ICBs. Perhaps most surprising to the field is that lung cancer can now be treated with PD-1 (CD279) and CTLA-4 (CD152) antagonists as a component of first line therapy. 10 years ago, the consensus among thoracic oncologists was that the solution for lung cancer was inhibitors of oncogene-driven signaling pathways and the field had dismissed the notion that lung cancer would be an immunologically responsive tumor.
  • Prospects for Combined Use of Oncolytic Viruses and CAR T-Cells Adam Ajina1 and John Maher2,3,4*

    Prospects for Combined Use of Oncolytic Viruses and CAR T-Cells Adam Ajina1 and John Maher2,3,4*

    J Immunother Cancer: first published as 10.1186/s40425-017-0294-6 on 21 November 2017. Downloaded from Ajina and Maher Journal for ImmunoTherapy of Cancer (2017) 5:90 DOI 10.1186/s40425-017-0294-6 REVIEW Open Access Prospects for combined use of oncolytic viruses and CAR T-cells Adam Ajina1 and John Maher2,3,4* Abstract With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful. This Review draws upon recent advances in the design of novel oncolytic viruses and CAR T-cells and provides a comprehensive overview of the synergistic potential of combination oncolytic virotherapy with CAR T-cell adoptive cell transfer for the management of solid tumours, drawing particular attention to the methods by which recombinant oncolytic viruses may augment CAR T-cell trafficking into the tumour microenvironment, mitigate or reverse local immunosuppression and enhance CAR T-cell effector function and persistence. Keywords: Oncolytic virus, Chimeric antigen receptor, CAR T-cell, Adoptive cell transfer, Combination strategies, Synergism, Solid tumours Background immune checkpoint inhibitors targeted against pro- This review focuses on the prospects for the synergistic grammed cell death protein 1 (PD-1; e.g.

  • CAR T-Cell Therapy for Acute Lymphoblastic Leukemia

    The Science Journal of the Lander College of Arts and Sciences Volume 12 Number 2 Spring 2019 - 2019 CAR T-cell Therapy for Acute Lymphoblastic Leukemia Esther Langner Touro College Follow this and additional works at: https://touroscholar.touro.edu/sjlcas Part of the Biology Commons, and the Pharmacology, Toxicology and Environmental Health Commons Recommended Citation Langner, E. (2019). CAR T-cell Therapy for Acute Lymphoblastic Leukemia. The Science Journal of the Lander College of Arts and Sciences, 12(2). Retrieved from https://touroscholar.touro.edu/sjlcas/vol12/ iss2/6 This Article is brought to you for free and open access by the Lander College of Arts and Sciences at Touro Scholar. It has been accepted for inclusion in The Science Journal of the Lander College of Arts and Sciences by an authorized editor of Touro Scholar. For more information, please contact [email protected]. CAR T-cell Therapy for Acute Lymphoblastic Leukemia Esther Langner Esther Langner will graduate in June 2019 with a Bachelor of Science degree in Biology and will be attending Mercy College’s Physician Assistant program. Abstract Despite all the available therapies, Acute Lymphoblastic Leukemia (ALL) remains extremely difficult to eradicate. Current available therapies, which include chemotherapy, radiation, and stem cell transplants, tend to be more successful in treating children than adults .While adults are more likely than children to relapse after treatment, the most common cause of treatment failure in children is also relapse. Improved outcomes for all ALL patients may depend upon new immunotherapies, specifically CAR T-cell therapy. CAR T-cell therapy extracts a patient’s own T-cells and modifies them with a CD19 antigen.
  • NK Cell-Based Immunotherapy for Hematological Malignancies

    NK Cell-Based Immunotherapy for Hematological Malignancies

    Journal of Clinical Medicine Review NK Cell-Based Immunotherapy for Hematological Malignancies Simona Sivori 1,2, Raffaella Meazza 3 , Concetta Quintarelli 4,5, Simona Carlomagno 1, Mariella Della Chiesa 1,2, Michela Falco 6, Lorenzo Moretta 7, Franco Locatelli 4,8 and Daniela Pende 3,* 1 Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy; [email protected] (S.S); [email protected] (S.C.); [email protected] (M.D.C.) 2 Centre of Excellence for Biomedical Research, University of Genoa, 16132 Genoa, Italy 3 Department of Integrated Oncological Therapies, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; raff[email protected] 4 Department of Hematology/Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, 00165 Rome, Italy; [email protected] (C.Q.); [email protected] (F.L.) 5 Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy 6 Integrated Department of Services and Laboratories, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; [email protected] 7 Department of Immunology, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; [email protected] 8 Department of Gynecology/Obstetrics and Pediatrics, Sapienza University, 00185 Rome, Italy * Correspondence: [email protected]; Tel.: +39-010-555-8220 Received: 20 September 2019; Accepted: 11 October 2019; Published: 16 October 2019 Abstract: Natural killer (NK) lymphocytes are an integral component of the innate immune system and represent important effector cells in cancer immunotherapy, particularly in the control of hematological malignancies. Refined knowledge of NK cellular and molecular biology has fueled the interest in NK cell-based antitumor therapies, and recent efforts have been made to exploit the high potential of these cells in clinical practice.
  • Advances in Evidence-Based Cancer Adoptive Cell Therapy

    Advances in Evidence-Based Cancer Adoptive Cell Therapy

    Review Article Page 1 of 18 Advances in evidence-based cancer adoptive cell therapy Chunlei Ge1, Ruilei Li1, Xin Song1, Shukui Qin2 1Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming 650118, China; 2Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing 210002, China Contributions: (I) Conception and design: X Song; (II) Administrative support: S Qin; (III) Provision of study materials or patients: C Ge; (IV) Collection and assembly of data: R Li; (V) Data analysis and interpretation: C Ge; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Professor Xin Song. Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming 650118, China. Email: [email protected]; Professor Shukui Qin. Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing 210002, China. Email: [email protected]. Abstract: Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field. This review also provided future research directions to make sure ACT widely available in clinic. Keywords: Adoptive cell therapy (ACT); non-specific cell therapy; specific cell therapy; dendritic cell-based therapy Submitted Mar 10, 2016.
  • Drug Price Forecast

    Drug Price Forecast

    Drug Price Forecast July-August 2018 © 2018 Vizient, Inc. All rights reserved. Introduction It is our privilege to share with you highlights from the July 2018 Vizient® Drug Price Forecast, which offers insights into areas of interest such as specialty pharmaceuticals, oncology drugs, infectious disease agents and drug shortages. The report provides our projections of pricing behavior for the period of Jan. 1 through Dec. 31, 2019, and discusses critical issues that will likely affect the cost and use of pharmaceuticals. The increasing expense of medications continues to invite criticism, scrutiny and calls for government intervention. Since the publication of the January 2018 edition of the Drug Price Forecast, several regulatory changes have been enacted. Some of these changes, such as increased Medicare reimbursement opportunities for biosimilars, are very positive for pharmacy providers, while others, including lower Medicare reimbursement for disproportionate share hospitals, are detrimental to the ongoing mission of improving access to high-quality care. It is important to understand the existing landscape as well as to anticipate changes that could add further complexity to pharmacy enterprises. Executive summary The Drug Price Forecast is our best estimate of the change in the cost of key pharmaceuticals between Jan. 1 and Dec. 31, 2019. The forecast focuses on pharmaceutical products used across multiple health-system settings, including inpatient and non-acute environments, and provides a year-over-year estimate of the expected price change. Price change predictions for contract and noncontract product segments are shown in Table 1, along with the overall drug price inflation number for existing drugs as calculated by Vizient.