A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia

AbstractIn elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens. Here, we present data from a phase I study conducted with DCP-001 in 12 advanced-stage elderly AML patients. Patients enrolled were in complete remission (CR1/CR2) (n = 5) or had smoldering disease (n = 7). All patients were at high risk of relapse and ineligible for post-remission intensification therapies. A standard 3 + 3 dose escalation design with extension to six patients in the highest dose was performed. Patients received four biweekly intradermal DCP-001 injections at different dose levels (10, 25, and 50 million cells DCP-001) and were monitored for clinical and immunological responses. Primary objectives of the study (feasibility and safety) were achieved with 10/12 patients completing the vaccination program. Treatment was well tolerated. A clear-cut distinction betwee n patients with and without detectable circulating leukemic blasts during the vaccination period was noted. Patients with no circulating blasts showed an unusually prolonged survival [median overall survival 36 mo...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Conclusion and Perspectives Being exquisitely regulated by “writers,” “erasers,” and “readers,” additional repelled proteins or miRNAs, m6A modification relates to nearly any step of mRNA metabolism, as well as ncRNA processing and circRNA translation. There is compelling evidence suggesting that m6A modification is especially critical in a variety of pathologic and physiologic immune responses including T cell homeostasis and differentiation, inflammation, and type I interferon production. Further results have indicated that aberrancies of interferon and Th17 frequencies in systemic lu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Personalized Dendritic Cell Vaccines—Recent Breakthroughs and Encouraging Clinical Results Beatris Mastelic-Gavillet, Klara Balint, Caroline Boudousquie, Philippe O. Gannon and Lana E. Kandalaft* Department of Oncology, Center for Experimental Therapeutics, Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults and has a five-year survival rate under 50%. Most patients will relapse even after complete remission is achieved through standard chemotherapy. Thus, one barrier in current AML therapy is how to target the minimal residual disease during remission. Recent developments in understanding cancer cell antigen presentation and immunosuppression have revealed the promise of cancer immunotherapy in activating immune responses to target residual disease. Each leukemia patient has a unique spectrum of cell surface antigens, which are mostly uncharacterized. If...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III Source Type: research
Introduction: In recent decades, a considerable number of tumor antigens have been characterized, including the leukemia-associated antigen, Wilm's tumor 1 (WT1). WT1 is found to be expressed at low levels in various normal tissues such as gonads, kidney and the hematopoietic system. However, it is highly overexpressed in various hematological malignancies and solid tumors, including in the majority of acute myeloid leukemia (AML) cases. OCV-501 is a human leukocyte antigen (HLA) class II-restricted helper peptide derived from the WT1 protein. This Phase II trial was conducted to evaluate the efficacy and safety of OCV-501...
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Immunotherapy and New Agents Source Type: research
Conclusion: We demonstrated the feasibility of MIL expansion from bone marrow mononuclear cells from AML patients. MIL are functionally active and mostly comprised of effector memory T cells. Confirmation of tumor cell antigen specificity will determine whether MIL may deploy a robust anti-tumor activity in vivo.DisclosuresKaryampudi: Iovance Biotherapeutics: Employment, Equity Ownership. Frank: Iovance Biotherapeutics: Employment, Equity Ownership. Blaskovich: Iovance Biotherapeutics: Equity Ownership. Chartier: Iovance Biotherapeutics: Equity Ownership.
Source: Blood - Category: Hematology Authors: Tags: 703. Adoptive Immunotherapy Source Type: research
In this study, we have shown that the lipid chaperones FABP4/FABP5 are critical intermediate factors in the deterioration of metabolic systems during aging. Consistent with their roles in chronic inflammation and insulin resistance in young prediabetic mice, we found that FABPs promote the deterioration of glucose homeostasis; metabolic tissue pathologies, particularly in white and brown adipose tissue and liver; and local and systemic inflammation associated with aging. A systematic approach, including lipidomics and pathway-focused transcript analysis, revealed that calorie restriction (CR) and Fabp4/5 deficiency result ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSIONSThe generation of hTERT‐DCs is feasible and vaccination with hTERT‐DCs appears to be safe and may be associated with favorable recurrence‐free survival. Cancer 2017. © 2017 American Cancer Society.
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
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