A Long-Acting Pharmacological Grade Interleukin-7 Molecule Logarithmically Accelerates CART Proliferation, Differentiation, and Tumor Killing

CART therapy is revolutionizing modern cancer therapy, with two anti-CD19 CARTs FDA-approved for relapsed/refractory B cell lymphoma/leukemia and many other CARTs for solid and liquid tumors currently undergoing clinical trials. However, in current clinical practice, suboptimal CART persistence and tumor killing permit tumor cell escape and, ultimately, disease relapse. Reasoning that a pro-lymphoid growth factor could promote CART efficacy, we supplemented UCART infusion with subcutaneous injections of the long-acting form of recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc, NT-I7) in vivo using a CD19+ lymphoma xenograft model.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 223 Source Type: research

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Mark E. Gray1,2*, James Meehan2,3, Paul Sullivan4, Jamie R. K. Marland4, Stephen N. Greenhalgh1, Rachael Gregson1, Richard Eddie Clutton1, Carol Ward2, Chris Cousens5, David J. Griffiths5, Alan Murray4 and David Argyle1 1The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom 2Cancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom 3School of Engineering and Physical Sciences, Institute of Sensors, Signals and Systems, Heriot-Watt Univer...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
For years, cancer treatment was dominated by chemotherapy, radiation therapy, and stem cell transplantation. New insights into genetic characteristics of leukemic cells have initiated the development of the chimeric antigen receptor (CAR) T-cell therapy. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukemia. In August 2018, the European Commission has approved the first CAR T-cell products – tisagenlecleucel (Kymriah®, Novartis) and axicabtagene ciloleucel (Yescarta®, Gilead) – for hematological n...
Source: Transfusion Medicine and Hemotherapy - Category: Hematology Source Type: research
In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conditions:   Acute Myelogenous Leukemia;   Acute Lymphocytic Leukemia;   Myelodysplastic Syndromes;   Non-Hodgkin Lymphoma;   Hodgkin Disease Interventions:   Procedure: Stem cell transplantation;   Drug: Itacitinib;   Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant;   Other: Human Activity Profile Sponsors:   Washington University School of Medicine;   Incyte Corporation Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusions:These data suggest that venetoclax treatment results in loss of naïve but not memory T cells. Venetoclax did not affect the viability, the induction or frequency of memory T cells. In human in vitro experiments and in an in vivo syngeneic tumor model venetoclax did not antagonize the therapeutic effect of anti-PD-1. Contrary to our initial hypothesis, we find that modulation of the immune system by venetoclax may support its potential use for immune-based cancer therapy, as memory T-cells can rapidly acquire effector and cytotoxic function to eliminate cancer cells. Taken together, we provide evidence that...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III Source Type: research
Conclusion: Taken together, our data suggest that BAFF-R is amenable to CAR T-cell therapy and that targeting it may add to existing alternative strategies to overcome relapse from CD19 antigen loss, such as CD22 CAR T cells. Future strategies combining dual targeting of CD19 and BAFF-R may also be effective.DisclosuresWang: Mustang Therapeutics: Other: Licensing Agreement, Patents &Royalties, Research Funding. Forman: Mustang Therapeutics: Other: Licensing Agreement, Patents &Royalties, Research Funding.
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster I Source Type: research
The evasion of apoptosis, or programmed cell death, is a hallmark of cancer, which promotes tumor initiation and progression. The evasion is in part attributable to the over-expression of anti-apoptotic proteins in the Bcl-2 family. In addition, chemotherapy and radiation can upregulate the expression of the Bcl-2 family in cancer cells, which renders them more resistance to cancer therapy. The most common Bcl-2 family member over-expressed in many solid tumor cells and a fraction of leukemia and lymphoma cells is Bcl-XL and its expression is also highly correlated with resistance to cancer therapy independent of p53 statu...
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster II Source Type: research
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