'Humanized' mice will lead to better testing of cancer immunotherapies

(University of Colorado Denver) New model reported in Oncogene, XactMice, uses human blood stem cells to grow a 'humanized' mouse immune system prior to tumor transplantation, allowing anti-cancer therapies to be tested in a much more human-like environment.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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This article, however, is more of a commentary on high level strategy and the effects of regulation, coupled with a desire to forge ahead rather than hold back in the matter of treating aging, thus I concur with much more of what is said than is usually the case. For decades, one of the most debated questions in gerontology was whether aging is a disease or the norm. At present, excellent reasoning suggests aging should be defined as a disease - indeed, aging has been referred to as "normal disease." Aging is the sum of all age-related diseases and this sum is the best biomarker of aging. Aging and its d...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions:In population-based analyses, the survival of t-MDS remains dismal with outcomes particularly worse with advancing age and following primary cancer sites that are typically managed with combined modality regimens including chemotherapy and radiation. Findings from the real-world population level data such as this should be used as outcome benchmarks in clinical trials to assess therapeutic effectiveness of experimental treatments.DisclosuresGerds: Apexx Oncology: Consultancy; Celgene: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Nazha: MEI: Consultancy. Carraway: Jazz: Speakers Bureau; FibroGen...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Myeloid Malignancies and Allogeneic Stem Cell Transplant Source Type: research
Natural killer (NK) cells are crucial effector cells of the innate immune system capable of rapidly recognizing and eliminating infected, stressed and malignant cells. NK cells are also the prime mediators of antibody-dependent cell-mediated cytotoxicity (ADCC), a potent mechanism of anti-viral immunity that has been applied to cancer therapy by targeting tumor-expressed surface antigens using monoclonal antibodies (mAbs). Classical ADCC is mediated by low affinity Fc-mediated engagement of NK cells via FcRIIIA (CD16A) and is modulated by differences in target antigen expression levels. While high potency of therapeutic mA...
Source: Blood - Category: Hematology Authors: Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster I Source Type: research
Adults diagnosed with acute myeloid leukemia have a poor prognosis, with only 30% surviving at five years. Despite advances in our understanding of the molecular underpinnings of AML, the chemotherapy backbone used to treat most patients (combination cytarabine and anthracycline) remains unchanged since 1973.With the goal of identifying a new differentiation therapy, we previously performed a small molecule phenotypic screen to find compounds that triggered myeloid maturation. Unexpectedly, our most active hits were inhibitors of the enzyme dihydroorotate dehydrogenase (DHODH). The DHODH-inhibitor brequinar demonstrated dr...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II Source Type: research
CONCLUSIONHigh-grade toxicity occurred after the DLT period in 41.3% of patients with R/R DLBCL, suggesting that the conventional concept of dose-limiting toxicity should be redefined in the era of modern cancer therapies. Besides, even if the phase 1 selection for clinical trials is very selective, it's necessary to better orient patients in hematology. In fact, 36.6% of patients were prematurely withdrawing of study which could be anticipated thanks to the identification of prognostics' factors. Although the objective response is only a secondary endpoint in phase I clinical trials, the median duration of participation i...
Source: Blood - Category: Hematology Authors: Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Poster II Source Type: research
This study investigated the effects of PTL and SSZ on unsorted, CD200+ and CD200- BCP-ALL subpopulations in the presence of MSC. Six MRD low risk and 4 risk cases were co-cultured on MSC, at a 2:1 ratio, 1 hour prior to addition of PTL at various doses up to 10mM. After 24 hours, cells were stained with Annexin V and PI and viability was assessed by flow cytometry. In the absence of MSC, low risk cases were slightly less sensitive to PTL with an IC50 of 2.23mM compared to risk ones (IC50 1.54mM, P=0.61). Interestingly, 4 of 6 low risk cases, which were less sensitive to PTL, had normal karyotypes, while the 2 responsive ca...
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster III Source Type: research
Conclusion: Homebound AHCT is safe and feasible with less than half of patients requiring inpatient admission. Patients required an average of two outpatient visits while receiving homebound care for blood products. Qualitative evaluations of the program by patients and caregivers were overwhelmingly positive. Based on these results we intend to expand the homebound program and investigate other potential biologic (microbiota diversity preservation) and economic benefits.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Poster I Source Type: research
Conclusions:Our study evaluated the quality of life in patients with myelofibrosis who have undergone bone marrow transplantation. We have shown that there is very little change in symptom burden over the first year following transplant in general; however, significant improvement was observed in MF specific symptoms, and in patients who had a high symptom burden at baseline. By one year 61% felt that their QoL was better than it was prior to transplant. Our findings suggest that many of the patients do not experience a significant decline in QoL at 1 year after alloSCT, and actually report that their QoL improves. Further...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Poster III Source Type: research
Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence following immunodepletion caused by common cancer therapies such as cytoreductive chemotherapy or radiation; however, the mechanisms governing this regeneration remain poorly understood. Despite this capacity, prolonged T cell deficiency is a major clinical hurdle in recipients of hematopoietic stem cell transplantation (HSCT) and can precipitate high morbidity and mortality from opportunistic infections, and may even facilitate malignant relapse. Our recent studies have revealed that innate lymphoid cells (ILCs) and endotheli...
Source: Blood - Category: Hematology Authors: Tags: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Signaling Pathways and Cells Protecting Against GVHD Source Type: research
Conclusion: Patients with AL amyloidosis have a worse HRQoL at diagnosis compared to US cancer and general adult population. Deficit in HRQoL was most prominent in the FWB domain of FACT-G and GPH domain of PROMIS-GH. Most domains of FACT-G and PROMIS-GH had strong and significant correlation. Patients achieving a CR to first-line therapy had significantly superior HRQoL at all FACT-G domains. Clinical trials in AL amyloidosis should include patient-reported HRQoL as a key endpoint and focus on the domains of physical health and functioning to assess meaningful benefit of novel therapies. Psychometric validation of FACT-G ...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Poster III Source Type: research
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