Advances in cell and gene therapy最新文献

{"title":"COVID-19 & allogeneic transplant: Activity and preventive measures for best outcomes in China","authors":"Zheng-Li Xu,&nbsp;Xiao-Jun Huang","doi":"10.1002/acg2.94","DOIUrl":"10.1002/acg2.94","url":null,"abstract":"<p>Coronavirus disease 2019 (COVID-19) is a highly transmissible viral illness caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). This virus triggered a pandemic crisis for health care systems worldwide. Initial experience from China indicated that patients with cancer had a higher risk of COVID-19 infection and poorer outcomes after developing COVID-19 than individuals without cancer.<span>¹</span> Patients with hematologic malignancy or receiving transplantation are immunosuppressed and may be particularly vulnerable to viral infections, and the hematology community faces unprecedented challenges.</p><p>The rapidly expanding COVID-19 pandemic has affected all aspects of medical activity, including hematopoietic stem cell transplantation (HSCT). Based on our current experience, preventive work of novel coronavirus is extremely important to mitigate its impact. Outside the epicentre (Wuhan), transplantation activity in China was not halted. We recommend preservation of transplantation activity under the premise of ensuring safety. This comment describes the possible impact of the current COVID-19 pandemic on transplantation activity and introduces interim precautions in our centre during the outbreak period.</p><p>During the outbreak, we maintained 80% of the transplant status. None of the patients or staff in our centre have been diagnosed with COVID-19, which demonstrates the importance and effectiveness of our preventive measures. We recommend preservation of transplant activity to the extent that the outbreak of COVID-19 allows. Otherwise, numerous patients will miss the optimal opportunity of transplantation and have poor prognosis. In addition to preserving transplantation activity, ensuring the safety of transplantation is a top priority. As mentioned above, transplantation is a procedure involving many aspects, and maximum emphasis should be placed on radical preventive and screening measures for each section of transplantation.</p><p>The comment was approved by the Institutional Review Board of Peking University People's Hospital.</p><p>The authors declare no competing financial interests.</p><p>X.-J. H. designed the review; Z.-L. X. and X.-J. H. wrote the manuscript; and they gave final approval for the manuscript.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.94","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38303162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert perspective: Highlights on myeloma cell therapy from the American Society of Hematology Annual Meeting 2019","authors":"Chutima Kunacheewa,&nbsp;Elisabet E. Manasanch","doi":"10.1002/acg2.93","DOIUrl":"10.1002/acg2.93","url":null,"abstract":"<p>Autologous stem cell transplantation has been part of standard of treatment in multiple myeloma for 2 decades. The data showed improving progression-free survival and overall survival. Despite the improvement of new drugs, myeloma patients continue to relapse New cell therapy, chimeric antigen receptor T-cell therapy have been explored in heavily pretreated patients. In this commentary, we highlight studies presented at the American Society of Hematology (ASH) Annual Meeting held in Orlando, FL in December 2019.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.93","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43417064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective platelet auditing: Resident compliance and the cost of training","authors":"Sarah Vossoughi,&nbsp;David Romoff,&nbsp;Joseph Schwartz","doi":"10.1002/acg2.87","DOIUrl":"10.1002/acg2.87","url":null,"abstract":"<p>Apheresis platelets are a product with high cost and limited supply commonly used for hematopoietic transplant patients. There is potential for both transfusion reactions and refractoriness associated with this product. Therefore, transfusion guideline compliance is closely monitored. This is a quality assurance review of a prospective platelet audit covering an 18-month period. Audit records created by trainees in their first post graduate year (PGY1) were compared to subsequent years. Multivariate regression analysis considered the variables of patient age, sex, PGY level, and platelet count. Financial modeling was derived for best case (low cost), base case (average cost), and worst case (high cost) scenarios. There were 1931 platelet doses requiring approval with 1122 (58%) compliant with hospital transfusion policy and 809 (42%) not compliant. Products ordered but not compliant with hospital policy were appropriately held from release by PGY1 physicians for 186/428 (43%) doses and 279/381 (73%) doses by PGY &gt; 1 physicians (<i>P</i> &lt; .01). Multivariate analysis demonstrated significance only in the categories of PGY level and platelet count. The ordered doses not compliant with hospital policy had an estimated minimal cost of $404 500. There were a disproportionately higher number of platelets released by the PGY1 group. Potential mitigation strategies for this include a closer level of oversight or hiring a patient blood manager to provide real-time metrics. Prevention of unnecessary transfusions is important in hematopoietic transplant patients both to prevent infections and decrease foreign antigen exposure and transfusion refractoriness.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.87","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48669996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspective: Cell therapy, SARS-CoV-2, COVID-19, and James Lind","authors":"Robert P. Gale","doi":"10.1002/acg2.88","DOIUrl":"10.1002/acg2.88","url":null,"abstract":"<p>The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic and resultant coronavirus infectious disease-2019 (COVID-19) create challenges and opportunities for physicians specializing in cell therapy and hematopoietic cell transplants. Recipients of these therapies are at high-infection risk because immune suppression and bone marrow failure from these therapies and their consequences such as cytokine release syndrome (CRS) and chronic graft-<i>versus</i>-host disease (G<i>v</i>HD) and from their underlying disease.</p><p>Little is known about the impact of the SARS-CoV-2 pandemic on cell therapies such as chimeric antigen receptor (CAR)-T-cell therapy. Because CAR-T-cell therapy uses autologous T cells there is no risk of SARS-CoV-2-infection from a donor. However, the recipient may be infected before, during, or after the therapy and unlikely to fare well if given immune suppressive drugs such as cyclophosphamide and fludarabine preinfusion. There may also transportation restrictions if the processing center is remote from the recipient, risk of infection from healthcare provider, family members, etc. Also, because CAR-T-cell recipients are at high risk of CRS, a complication shared with severe COVID-19 and the combination could be fatal. Although there are reasonably convincing data of safety and efficacy on interleukin-6 antagonists in CRS related to CAR-T-cell therapy, most data suggest that this approach is ineffective in COVID-19-related pneumonia.<span>^{1, 2}</span> The US Food and Drug Administration (FDA) has approved a phase-3 placebo-controlled trial of tocilizumab in COVID-19 pneumonia (https://clinicaltrials.gov/ct2/show/NCT04320615); I await results. Elsewhere, my colleagues and I review the possible role of mesenchymal stromal cells in COVID-19-related acute respiratory distress syndrome.<span>³</span> Others are studying placenta or umbilical cord-derived natural killer (NK)-cells (https://www.europeanpharmaceuticalreview.com/news/116794/us-researchers-to-study-stem-cell-therapy-in-covid-19-patients/). Preliminary results of phase-2 trails are being reported, but data are mostly uninterpretable regarding efficacy with appropriate controls. If cell-therapy-based approaches prove safe and effective, operationalizing this will involve hematologists, especially those in cell therapy and/or hematopoietic cell transplantation.</p><p>There are few data about SARS-CoV-2-infection and COVID-19 in persons with hematological cancers. My Chinese colleagues and I studied several aspects of this in Wuhan, epi-center of the SARS-CoV-2 pandemic and in Hubei province. In one study in &gt; 500 persons with chronic myeloid leukemia (CML), we found only five cases of COVID-19.<span>⁴</span> Although this case rate was substantially higher than the case rate in normals in Hubei province, it is obviously not a serious issue in persons with CML. Risk factors included exposure to someone infected with SAR","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.88","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38303161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward “off-the-shelf” allogeneic CAR T cells","authors":"Blake T. Aftab,&nbsp;Barbra Sasu,&nbsp;Janani Krishnamurthy,&nbsp;Eric Gschweng,&nbsp;Vincent Alcazer,&nbsp;Stéphane Depil","doi":"10.1002/acg2.86","DOIUrl":"10.1002/acg2.86","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in the field of immuno-oncology. Many potential issues are apparent for autologous CAR T cell therapy, such as time for manufacturing and need for interim therapies in progressing patients, wide variations in terms of quality and quantity of T cells, and difficulty to obtain enough cells for redosing. “Off-the-shelf” allogeneic CAR T cells premanufactured from third-party donors may theoretically provide solutions to these different problems. However, allogeneic T cells possess foreign immunological identities that can lead to histocompatibility considerations such as graft-versus-host disease and rejection of allogeneic cells. This review outlines the major recent advances for off-the-shelf T cell therapies currently in clinical trials or in preclinical development and describes strategies for reengineering or selecting specific T cell immune identities to create safe and efficient immunotherapies for patients.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.86","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46205292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When to consider allogeneic transplant for chronic myeloid leukemia","authors":"Daniel Egan,&nbsp;Jerald Radich","doi":"10.1002/acg2.85","DOIUrl":"10.1002/acg2.85","url":null,"abstract":"<p>Allogeneic stem cell transplantation (ASCT) has historically been recognized as the only curative therapy for chronic myeloid leukemia (CML). However, the remarkable success of tyrosine kinase inhibitors (TKIs) which result in excellent long-term disease control in the majority of newly diagnosed CML patients, has forever changed the treatment strategy of CML. However, TKIs fail some patients, due to treatment resistance, relapse, progression, and toxicity, and for these patients ASCT remains a potentially curative option. In this review, we will discuss the indications and outcomes of allogeneic transplant for patients with CML in the modern era.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.85","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44753989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRUCKS, the fourth-generation CAR T cells: Current developments and clinical translation","authors":"Markus Chmielewski,&nbsp;Hinrich Abken","doi":"10.1002/acg2.84","DOIUrl":"10.1002/acg2.84","url":null,"abstract":"<p>The overriding goal of adoptive cell therapy with chimeric antigen receptor (CAR) redirected T cells in oncology is to eliminate cancer cells from infiltrated tissues. Clinical trials document that this form of immunotherapy can induce lasting remissions of hematologic malignancies; however, the successes could not yet be transferred to the treatment of solid tumors. In this situation, modulating the immune regulation within the solid tumor tissue is thought to be a key point. In order to induce a pro-inflammatory milieu CAR T cells were additionally engineered to release a transgenic cytokine upon CAR signaling in the targeted tumor tissue. Such TRUCKs (“T cells redirected for antigen-unrestricted cytokine-initiated killing”), also called “4th generation” CAR T cells, combine the direct antitumor attack of the CAR T cell with the immune modulating capacities of the delivered cytokine. Through CAR-induced release, the cytokine is ideally deposited in the targeted tissue alleviating systemic side effects. The TRUCK concept is currently explored using a panel of cytokines, including IL-7, IL-12, IL-15, IL-18, IL-23, and combinations thereof, and is entering early phase trials. Future developments will expand the application to a broader panel of released proteins converting CAR T cells to “living factories” of therapeutically active, locally deposited products with the potential to eliminate some clinical deficits of the currently used CAR T cells in the field of solid tumors.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.84","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47573396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular aberrations in myelodysplastic syndromes","authors":"Nikesh N. Shah,&nbsp;Rami S. Komrokji","doi":"10.1002/acg2.83","DOIUrl":"10.1002/acg2.83","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.83","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45271662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary central nervous system lymphoma: Consensus, controversies, and future directions","authors":"Talal Hilal","doi":"10.1002/acg2.82","DOIUrl":"10.1002/acg2.82","url":null,"abstract":"<p>Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin lymphoma for which multiple modalities of treatment are often used, including radiation therapy, chemotherapy with or without autologous stem cell transplant (ASCT), and immunotherapy. The optimal approach to the treatment of PCNSL varies based on patient fitness, age, and comorbid conditions. The cornerstone of therapy remains high-dose methotrexate with or without other chemotherapeutic agents that have activity against PCNSL. Consolidation therapy in the form of whole brain radiation and/or ASCT is offered to select patients. Almost half of the patients experience disease relapse, and the approach to patients with relapsed/refractory disease varies depending on the timing of relapse and the initial treatment. In recent years, several novel agents targeting the B-cell receptor (BCR) pathway have shown activity in early phase trials prompting their ongoing evaluation in larger prospective trials in combinations, as well as their use in the relapsed/refractory setting. Immunotherapy beyond rituximab is an emerging treatment modality that may become part of the therapeutic arsenal. There are various controversial aspects to the optimal treatment of PCNSL, including the use of rituximab, intrathecal chemotherapy, and consolidation therapy. These controversies and the evidence behind the various treatment modalities used in PCNSL are explored in this review.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.82","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43707921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA in lymphomas: Era of precision medicine","authors":"Avyakta Kallam,&nbsp;Jayanth Adusumalli,&nbsp;Kai Fu,&nbsp;James O. Armitage","doi":"10.1002/acg2.81","DOIUrl":"10.1002/acg2.81","url":null,"abstract":"<p>Non-Hodgkin's lymphomas are heterogeneous lymphoid malignancies, usually with an excellent prognosis. Aggressive B-cell lymphomas, such as diffuse large B-cell lymphomas, are treated with a curative intent with first-line therapy achieving a cure rate in about 70% of patients. Indolent lymphomas, such as follicular lymphoma (FL), are considered less curable, with the goal of treatment directed toward inducting deep remissions. With treatment strategies evolving more toward precision medicine, there is a need for better diagnostic, prognostic biomarkers. Circulating tumor DNA (ct-DNA) shed into the blood by tumor cells can be used as a marker for identification of tumor, assessment of tumor response, and to predict long-term outcomes. Recent studies have demonstrated the potential of these techniques as a prognostic tool. We review the clinical data supporting the role of ct-DNA in non-Hodgkin's lymphomas.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49028987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}