Should immunologic strategies be incorporated into frontline ALL therapy?

Publication date: Available online 25 September 2018Source: Best Practice &Research Clinical HaematologyAuthor(s): Cecilie Utke Rank, Wendy StockAbstractSurvival rates in adult patients with acute lymphoblastic leukemia (ALL) have markedly improved during the past decade. The one-size-fits-all-ages approach has been replaced with adaptation of pediatric-inspired treatment protocols for younger adults. Yet different treatment strategies for older patients are needed due to chemotherapy-related toxicities. A new era of immunotherapy has arrived, offering opportunities for targeted treatments for ALL subtypes. While CD20 targeting with rituximab has been demonstrated to improve survival when combined with chemotherapy, it has little activity as a single agent in ALL. In contrast, antibody targeting of CD19 and CD22 with blinatumomab and inotuzumab ozogamicin, respectively, has had remarkable single-agent activity in the relapsed setting. Studies are now underway to test these agents in combination with chemotherapy in the frontline setting. The goal of these studies is to improve event-free survival and overall survival by using these approaches in the frontline to eradicate minimal residual disease and, particularly in older adults with ALL, to reduce treatment-related toxicity by limiting the exposure to traditional multi-agent chemotherapy with its attendant toxicities. This review focuses on new immunotherapeutic treatment options and strategies for frontline treatment, ...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research

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In conclusion, T cells from lymphoma patients are reduced in number and have functional defects following treatment with certain chemotherapy regimens, also reducing AFM11 efficacy. Importantly, AFM11 was still able to trigger B-cell-directed T-cell immunity in all treatment groups.
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Refractory and relapsed acute myeloid leukemia (AML) and T-lineage leukemia have poor prognosis and limited therapeutic options. Adoptive cellular immunotherapies are emerging as an effective treatment for patients with chemotherapy refractory hematological malignancies. Indeed, the use of unselected donor lymphocyte infusions has demonstrated successes in treating patients with AML and T-lineage leukemia post–allogeneic transplantation. The development of ex vivo manipulation techniques such as genetic modification or selection and expansion of individual cellular components has permitted the clinical translation of...
Source: The Cancer Journal - Category: Cancer & Oncology Tags: Review Articles Source Type: research
Abstract Refractory and relapsed acute myeloid leukemia (AML) and T-lineage leukemia have poor prognosis and limited therapeutic options. Adoptive cellular immunotherapies are emerging as an effective treatment for patients with chemotherapy refractory hematological malignancies. Indeed, the use of unselected donor lymphocyte infusions has demonstrated successes in treating patients with AML and T-lineage leukemia post-allogeneic transplantation. The development of ex vivo manipulation techniques such as genetic modification or selection and expansion of individual cellular components has permitted the clinical tr...
Source: Cancer Journal - Category: Cancer & Oncology Authors: Tags: Cancer J Source Type: research
This study included 18 buffy coats collected from volunteer blood donors admitted to the blood transfusion service of IRCCS Bambino Gesù Pediatric Hospital after obtaining informed consent. The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014) and conducted in accordance with the ethical principles stated in the Declaration of Helsinki. Cells Lines and Cell Culture NK-92 (malignant non-Hodgkin's lymphoma), K562 (chronic myelogenous leukemia, CD19−), Jurkat (acute T cell leukemia, CD19−) Karpas 299 (Human Non-Hodgkin's Ki-positive Large Cell ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Lei Shang1,2 and Minjie Wei1* 1School of Pharmacy, China Medical University, Shenyang, China 2Shenyang Medical College, Shenyang, China The protein lysine methyltransferase SMYD2 has recently emerged as a new enzyme modulate gene transcription or signaling pathways, and involved into tumor progression. However, the role of SMYD2 in drug resistant is still not known. Here, we found that inhibition of SMYD2 by specific inhibitor could enhance the cell sensitivity to cisplatin (CDDP), but not paclitaxel, NVB, and VCR in non-small cell lung cancer (NSCLC). Further study showed that SMYD2 and its substrates were overex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) have produced impressive minimal residual disease–negative (MRD-negative) complete remission (CR) rates in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the factors associated with durable remissions after CAR T-cell therapy have not been fully elucidated. We studied patients with relapsed/refractory B-ALL enrolled in a phase 1/2 clinical trial evaluating lymphodepletion chemotherapy followed by CD19 CAR T-cell therapy at our institution. Forty-five (85%) of 53 patients who received CD19 ...
Source: Blood - Category: Hematology Authors: Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research
We report that the bifunctional compounds enhance the interactions between primary human neutrophils and A. fumigatus in vitro, using three microfluidic assay platforms. The bifunctional compounds significantly enhance the recruitment of neutrophils, increase hyphae killing by neutrophils in a uniform concentration of drug, and decrease hyphal tip growth velocity in the presence of neutrophils compared to the antifungal targeting moiety alone. We validated that the bifunctional compounds are also effective in vivo, using a zebrafish infection model with neutrophils expressing the appropriate EM receptor. We measured signif...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractThe advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T cells for targeted cancer therapy. CAR T cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration: one for the treatment of pediatric acute lymphoblastic leukemia (ALL) and the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T cell therapy is still in its early days and face...
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research
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