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https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#1
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#2
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#3
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27797968/new-strategies-in-multiple-myeloma-immunotherapy-as-a-novel-approach-to-treat-patients-with-multiple-myeloma
#4
Paola Neri, Nizar J Bahlis, Sagar Lonial
Multiple myeloma is a B-cell malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Although new therapeutic options introduced in recent years have resulted in improved survival outcomes, multiple myeloma remains incurable for a large number of patients, and new treatment options are urgently needed. Over the last 5 years, there has been a renewed interest in the clinical potential of immunotherapy for the treatment of multiple myeloma. Clinical progression of myeloma is known to be associated with progressive immune dysregulation and loss of immune surveillance that contribute to disease progression in association with progressive genetic complexity, rendering signaling-based treatments less effective...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27782084/measles-to-the-rescue-a-review-of-oncolytic-measles-virus
#5
REVIEW
Sarah Aref, Katharine Bailey, Adele Fielding
Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis...
October 22, 2016: Viruses
https://www.readbyqxmd.com/read/27717026/epidemiology-of-bloodstream-infections-in-patients-with-myeloma-receiving-current-era-therapy
#6
Benjamin W Teh, Simon J Harrison, Monica A Slavin, Leon J Worth
BACKGROUND: Bloodstream infections (BSIs) are a significant complication of treatment for multiple myeloma (MM). The objective of this study was to define the epidemiology of BSI with current era MM treatment regimens, including immunomodulatory drugs, proteasome inhibitors and autologous haematopoietic stem cell transplantation (ASCT). METHODS: Clinical and microbiology records of patients with MM diagnosed between 2008 and 2012 were reviewed using a standardised tool to capture patient demographics, myeloma characteristics and BSI characteristics (type, severity, outcomes)...
September 26, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27696265/role-of-the-immune-response-in-disease-progression-and-therapy-in-multiple-myeloma
#7
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27610224/recent-advances-in-understanding-multiple-myeloma
#8
REVIEW
Binod Dhakal, Saulius Girnius, Parameswaran Hari
There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment...
2016: F1000Research
https://www.readbyqxmd.com/read/27597852/challenges-in-the-role-of-gammaglobulin-replacement-therapy-and-vaccination-strategies-for-hematological-malignancy
#9
REVIEW
Silvia Sánchez-Ramón, Fatima Dhalla, Helen Chapel
Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are prone to present with antibody production deficits associated with recurrent or severe bacterial infections that might benefit from human immunoglobulin (Ig) (IVIg/SCIg) replacement therapy. However, the original IVIg trial data were done before modern therapies were available, and the current indications do not take into account the shift in the immune situation of current treatment combinations and changes in the spectrum of infections...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27557809/antibody-engineering-therapeutics-2016-the-antibody-society-s-annual-meeting-december-11-15-2016-san-diego-ca
#10
James W Larrick, Mark R Alfenito, Jamie K Scott, Paul W H I Parren, Dennis R Burton, Andrew R M Bradbury, Cynthia A Lemere, Anne Messer, James S Huston, Paul J Carter, Trudi Veldman, Kerry A Chester, Janine Schuurman, Gregory P Adams, Janice M Reichert
Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement...
August 24, 2016: MAbs
https://www.readbyqxmd.com/read/27533084/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#11
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27506540/the-immunotherapy-era-of-myeloma-monoclonal-antibodies-vaccines-and-adoptive-t-cell-therapies
#12
REVIEW
Valentina Hoyos, Ivan Borrello
The treatment of multiple myeloma has evolved significantly over the last decades from primarily alkylator-based chemotherapeutic agents with minimal efficacy to the introduction of more effective agents including immune modulators and proteasome inhibitors, which have changed the landscape of therapy for this disease. We are now entering a new era that will increasingly integrate immunotherapy into standard treatment. This review discusses the current immune-based strategies currently approved, as well as various immune approaches being actively investigated including monoclonal antibodies, checkpoint inhibitors, vaccines, and adoptive T-cell therapies...
September 29, 2016: Blood
https://www.readbyqxmd.com/read/27487784/epidemiology-of-invasive-pneumococcal-infections-manifestations-incidence-and-case-fatality-rate-correlated-to-age-gender-and-risk-factors
#13
Erik Backhaus, Stefan Berg, Rune Andersson, Gunilla Ockborn, Petter Malmström, Mats Dahl, Salmir Nasic, Birger Trollfors
BACKGROUND: Incidence, manifestations and case-fatality rate (CFR) of invasive pneumococcal disease (IPD) vary with age and comorbidities. New vaccines, changing age distribution, prolonged survival among immunocompromised patients and improved sepsis management have created a need for an update of basic facts to inform vaccine recommendations. METHODS: Age, gender and comorbidities were related to manifestations and death for 2977 consecutive patients with IPD in a Swedish region with 1...
August 3, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27464688/development-of-human-monoclonal-antibodies-against-respiratory-syncytial-virus-using-a-high-efficiency-human-hybridoma-technique
#14
Gabriela Alvarado, James E Crowe
Human monoclonal antibodies against RSV have high potential for use as prophylaxis or therapeutic molecules, and they also can be used to define the structure of protective epitopes for rational vaccine design. In the past, however, isolation of human monoclonal antibodies was difficult and inefficient. Here, we describe contemporary methods for activation and proliferation of primary human memory B cells followed by cytofusion to non-secreting myeloma cells by dielectrophoresis to generate human hybridomas secreting RSV-specific monoclonal antibodies...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27402426/secondary-immunodeficiency-in-lymphoproliferative-malignancies
#15
REVIEW
Vanda Friman, Ola Winqvist, Cecilie Blimark, Petra Langerbeins, Helen Chapel, Fatima Dhalla
Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti-inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections...
September 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27364264/vaccination-in-multiple-myeloma-review-of-current-literature
#16
Andinet Alemu, John O Richards, Martin K Oaks, Michael A Thompson
Multiple myeloma is a cancer of the immune system. Infection is a major cause of morbidity and mortality in patients with multiple myeloma. Some of these infections are preventable by vaccines available to the general population. However, little is known about the clinical effectiveness of these vaccines in patients with multiple myeloma, and the cellular and humoral immune response to vaccination has not been well characterized, especially in conjunction with modern myeloma therapies. The present report reviews the basics of multiple myeloma and the immune system, the available evidence on the immunologic response of patients with multiple myeloma after vaccination, and current practice recommendations regarding specific vaccines...
June 8, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27249701/moving-beyond-autologous-transplantation-in-multiple-myeloma-consolidation-maintenance-allogeneic-transplant-and-immune-therapy
#17
Amrita Krishnan, Ravi Vij, Jesse Keller, Binod Dhakal, Parameswaran Hari
For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses...
2016: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/27058703/immune-therapy-in-multiple-myeloma
#18
Katarina Luptakova, David Avigan
Although the advent of biologic therapies has resulted in improved outcomes for patients with multiple myeloma (MM), patients ultimately develop progressively resistant disease. As such, novel approaches are needed. There has been a renewed focus on the development of therapies that would allow redirection of patients' own immune systems to target malignant myeloma cells. Compared with healthy individuals, patients with MM exhibit immune dysregulation and an impaired capacity to develop antitumor immunity. Tumor cells induce tolerance by exploiting native immune pathways responsible for preventing autoimmunity and maintaining immunologic equilibrium...
November 2015: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/26962517/preparation-of-monoclonal-antibodies-against-mannosylated-lipoarabinomannan-manlam-a-surface-antigen-of-bcg-vaccine-produced-in-iran
#19
Mohammad Taghikhani, Rasul Moukhah
BACKGROUND: Bacille Calmette-Guerin (BCG) vaccine is the only vaccine that is used against Mycobacterium tuberculosis, but its efficacy is limited in mycobacterium-endemic regions. One of the major antigens present on the cell envelope of the vaccine that suppresses the immune system is mannosylated lipoarabinomannan (ManLAM). MATERIALS AND METHODS: In this study, we immunized 4-week-old mice with sonicated BCG vaccine injected intraperitoneally two times at an interval of 2 weeks and with ManLAM antigen injected intravenously and then extracted the spleen cells of the immunized mice...
2016: Advanced Biomedical Research
https://www.readbyqxmd.com/read/26912783/poor-correlation-between-pneumococcal-igg-and-igm-titers-and-opsonophagocytic-activity-in-vaccinated-patients-with-multiple-myeloma-and-waldenstrom-s-macroglobulinemia
#20
Johanna Karlsson, Lucy Roalfe, Harriet Hogevik, Marta Zancolli, Björn Andréasson, David Goldblatt, Christine Wennerås
Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n= 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA...
April 2016: Clinical and Vaccine Immunology: CVI
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