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Efficacy of Oral Immunotherapy in Patients with Multiple Food Allergies

SP Wilson, et al. (2013)
Journal of Allergy and Clinical Immunology

  • There is no summary for this article.
Medical and Health Science
 Abstract

Gene Expression Profile Correlates with T-Cell Infiltration and Relative Survival in Glioblastoma Patients Vaccinated with Dendritic Cell Immunotherapy

RM Prins, et al. (2010)
Clinical Cancer Research

Summary

  • To assess the feasibility, safety, and toxicity of autologous tumor lysate-pulsed dendritic cell (DC) vaccination and toll-like receptor (TLR) agonists in patients with newly diagnosed and recurrent glioblastoma.
  • Twenty-three patients with glioblastoma (WHO grade IV) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every 3 months until tumor progression.
  • Our results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies.
Medical and Health Science
 Abstract

The Emerging Protumor Role of    T Lymphocytes: Implications for Cancer Immunotherapy

M Rei, DJ Pennington, B Silva-santos (2015)
Cancer Research

Summary

  • Among the various lymphocyte subsets implicated in protection against cancer are γδ T lymphocytes, which can kill tumor cells and secrete potent antitumor cytokines.
  • By contrast, recent reports have revealed an unexpected series of protumor functions of γδ T cells in mouse models and human patients.
  • A common mediator of such functions appears to be the cytokine IL17, whose pathogenic effects can override the antitumor immune response orchestrated by IFNγ.
Medical and Health Science
 Abstract

Low-Dose Interleukin-2 Immunotherapy Does Not Improve Outcome of Patients Age 60 Years and Older With Acute Myeloid Leukemia in First Complete Remission: Cancer and Leukemia Group B Study 9720

MR Baer, et al. (2008)
Journal of Clinical Oncology

Summary

  • AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells.
  • Grade 4 toxicities during rIL-2 therapy included thrombocytopenia (65%) and neutropenia (64%), and grade 3 toxicities included anemia (33%), infection (24%) and malaise/fatigue (14%).
  • Patients in both arms had similar distributions of both disease-free (combined median = 6.1 months; P = .47) and overall survival (combined median = 14.7 months; P = .61) after random assignment.
Medical and Health Science
 Abstract

New Directions in Immunotherapy

L Cox, et al. (2013)
Current Allergy and Asthma Reports

Summary

  • The efficacy of these 2 routes appears comparable, but the safety profile with SLIT is more favorable allowing for home administration and requiring less patient time.
  • Research with oral immunotherapy (OIT) for food allergies suggest that many patients can be desensitized during treatment, but questions remain about whether this can produce long term tolerance.
  • These newer approaches may increase the utilization and adherence to AIT because the multi-year treatment requirement of currently available AIT is a likely deterrent for initiating and adhering to treatment.
Medical and Health Science
 Abstract

Polymeric microparticles for sustained and local delivery of antiCD40 and antiCTLA-4 in immunotherapy of cancer

S Rahimian, et al. (2015)
Biomaterials

Summary

  • Local delivery of potent immunomodulatory antibodies avoids unwanted systemic side effects while retaining their anti-tumor effects.
  • Microparticles based on poly(lactic-co-hydroxymethyl-glycolic acid) (pLHMGA) and loaded with two distinct types of immunomodulatory antibodies (CTLA-4 antibody blocking inhibitory receptors on T cells or CD40 agonistic antibody stimulating dendritic cells) were prepared by double emulsion solvent evaporation technique.
  • The in vitro release profile of antiCD40 and antiCTLA-4 from microparticles showed a burst release of about 20% followed by a sustained release of the content up to 80% of the loading in around 30 days.
Biology
Engineering
Physics
 Abstract

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

JH Sampson, et al. (2008)
Seminars in Immunology

Summary

  • We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction is an efficacious immunotherapy in syngeneic murine models, but patients with MGs have a profound immunosuppression that may inhibit the ability of antigen presenting cells (APCs), even those generated ex vivo, to induce EGFRvIII-specific immune responses.
  • These trials demonstrated that vaccines targeting EGFRvIII are capable of inducing potent T- and B-cell immunity in these patients, and lead to an unexpectedly long survival time.
  • Most importantly, vaccines targeting EGFRvIII were universally successful at eliminating tumor cells expressing the targeted antigen without any evidence of symptomatic collateral toxicity.
Medical and Health Science
 Abstract

Localized Oncolytic Virotherapy Overcomes Systemic Tumor Resistance to Immune Checkpoint Blockade Immunotherapy

D Zamarin, et al. (2014)
Science Translational Medicine

Summary

  • Recent studies also suggest that lymphocytic responses may identify patients more likely to benefit from therapies targeting immune checkpoints, suggesting that therapeutic efficacy of immune checkpoint blockade can be enhanced through strategies that induce tumor inflammation.
  • Combination therapy with localized NDV and systemic CTLA-4 blockade led to rejection of preestablished distant tumors and protection from tumor rechallenge in poorly immunogenic tumor models, irrespective of tumor cell line sensitivity to NDV-mediated lysis.
  • Therapeutic effect was associated with marked distant tumor infiltration with activated CD8(+) and CD4(+) effector but not regulatory T cells, and was dependent on CD8(+) cells, natural killer cells, and type I interferon.
Biology
Medical and Health Science
 Abstract

Immune Modulation by Ionizing Radiation and its Implications for Cancer Immunotherapy

E Friedman (2002)
Current Pharmaceutical Design

Summary

  • Ionizing radiation exhibits immunomodulatory properties, which could portend a future collaboration of cancer immunotherapy with radiation therapy.
  • Radiation upregulates expression of immunomodulatory surface molecules (MHC, costimulatory molecules, adhesion molecules, death receptors, heat shock proteins) and secretory molecules (cytokines, inflammatory mediators) in tumor, stromal, and vascular endothelial cells.
  • With a thorough understanding of this phenomenon, we believe that ionizing radiation could be optimized for use with cancer vaccines and generate tumor antigen-specific cellular immunity.
Medical and Health Science
 Abstract

Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype–positive rheumatoid arthritis patients

H Benham, et al. (2015)
Science Translational Medicine

Summary

  • At 1 month after treatment, we observed a reduction in effector T cells and an increased ratio of regulatory to effector T cells; a reduction in serum interleukin-15 (IL-15), IL-29, CX3CL1, and CXCL11; and reduced T cell IL-6 responses to vimentin(447-455)-Cit450 relative to controls.
  • Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and DAS28 decreased within 1 month in Rheumavax-treated patients with active disease.
  • This exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified DCs exposed to citrullinated peptides, and provides rationale for further studies to assess clinical efficacy and antigen-specific effects of autoantigen immunomodulatory therapy in RA.
Biology
Medical and Health Science
 Abstract

Tau-Focused Immunotherapy for Alzheimers Disease and Related Tauopathies

E Sigurdsson (2009)
Current Alzheimer Research

Summary

  • Immunotherapies targeting the amyloid-beta (Abeta) peptide in Alzheimer's disease (AD) have consistently been effective in mouse studies and shown promise in clinical trials, although some setbacks have occurred.
  • More recent autopsy data from a few subjects suggests that clearance of Abeta plaques may not halt cognitive deterioration once impairments are evident, emphasizing the need for other more effective approaches at that stage of the disease.
  • Our findings in two tangle mouse models indicate that active immunization targeting an AD phospho-tau epitope reduces aggregated tau in the brain and prevents/slows progression of the tangle-related behavioral phenotype, including cognitive impairment.
Medical and Health Science
 Abstract

Specific immunotherapy for respiratory allergy: state of the art according to current meta-analyses

E Compalati, et al. (2009)
Annals of Allergy, Asthma & Immunology

Summary

  • We evaluated the quality of individual meta-analyses by following the recommendations of the Cochrane Collaboration and the QUOROM (Quality of Reporting of Meta-analyses) statement.
  • All 7 meta-analyses reported a reduction in symptom and medication scores, although 1 sublingual immunotherapy meta-analysis did not find a significant size effect, probably because of the inclusion criteria.
  • According to evidence-based criteria, specific immunotherapy can be recommended for the treatment of respiratory allergy because of its efficacy in reducing asthma and rhinitis symptoms.
Medical and Health Science
 Abstract

Surveillance of systemic reactions to subcutaneous immunotherapy injections: year 1 outcomes of the ACAAI and AAAAI Collaborative Study

DI Bernstein, et al. (2010)
Annals of Allergy, Asthma & Immunology

Summary

  • The SR events were classified as mild (grade 1: cutaneous or upper respiratory symptoms), moderate (grade 2: asthma with reduced lung function), or severe (grade 3: life-threatening airway compromise or hypotension).
  • No fatal reactions to SCIT injections were identified during the first 12 months, although 6 SCIT fatal reactions were reported retrospectively between 2001 and 2007.
  • This surveillance study will continue to monitor SCIT adverse events in parallel with vigorous efforts instituted by members of professional organizations aimed at reducing the risk of severe reactions.
Medical and Health Science
 Abstract

Antiangiogenic Agents Can Increase Lymphocyte Infiltration into Tumor and Enhance the Effectiveness of Adoptive Immunotherapy of Cancer

RK Shrimali, et al. (2010)
Cancer Research

Summary

  • Adoptive cell transfer (ACT)-based immunotherapies can mediate objective cancer regression in animal models and in up to 70% of patients with metastatic melanoma; however, it remains unclear whether the tumor vasculature impedes the egress of tumor-specific T cells, thus hindering this immunotherapy.
  • Disruption of the proangiogenic interaction of vascular endothelial growth factor (VEGF) with its receptor (VEGFR-2) has been reported to "normalize" tumor vasculature, enhancing the efficacy of chemotherapeutic agents by increasing their delivery to the tumor intersitium.
  • These studies provide a rationale for the exploration of combining antiangiogenic agents with ACT for the treatment of patients with cancer.
Medical and Health Science
 Abstract

Releasing the Brakes on Cancer Immunotherapy

A Ribas (2015)
New England Journal of Medicine

Summary

  • After mapping out the molecular mechanisms of T-cell antigen recognition, regulation, and function in the 1980s and 1990s, immunologist James P. Allison hypothesized that blocking negative immune regulators (checkpoints) would give the human immune system the power to fight cancer.
  • His testing of this hypothesis in preclinical models led to the clinical development of a new generation of active agents for cancer treatment.
  • In some subgroups of patients, unleashing native immune-system cells to fight cancer now provides a realistic chance of long-term remission.
Medical and Health Science
 Abstract

Oral immunotherapy in cow's milk allergic patients: course and long-term outcome according to asthma status

A Elizur, et al. (2015)
Annals of Allergy, Asthma & Immunology

Summary

  • Children at least 6 years old with (n = 101) and without (n = 93) asthma and IgE-mediated cow's milk allergy, undergoing milk oral immunotherapy from April 2010 to December 2011, were compared.
  • Before immunotherapy, patients with asthma, regardless of severity, had more anaphylactic reactions (84.2% vs 64.5%, P = .003), emergency department visits (68.3% vs 51.6%, P = .02), and hospital admissions (32.7% vs 18.3%, P = .03) compared with patients without asthma.
  • Moderate to severe asthma was associated with a lower likelihood of reaching full desensitization (51.5% vs 68.8%, P = .019), but most patients with asthma (87 of 101, 86.1%), regardless of severity, reached a dose likely to protect them against accidental exposure.
Medical and Health Science
 Abstract

Immunology and immunotherapy of colorectal cancer

P Dalerba, et al. (2003)
Critical Reviews in Oncology/Hematology

Summary

  • A careful evaluation of histopathological studies on intra-epithelial infiltration by T cells in primary tumours, together with the analysis of HLA expression by colorectal cancer cells, suggest that anti-tumour T cell immune responses may take place in vivo in those patients, influencing prognosis and shaping the tumour immunological profile.
  • The molecular characterisation of tumour antigens expressed by colorectal carcinomas, together with improved understanding of mechanisms of the immune response and more sensitive methods for the in vivo detection of T cell responses, are now allowing researchers to design new and more effective vaccination protocols, with encouraging preliminary results.
  • By drawing together the experimental evidence from different research fields, this review provides support for the concept that colorectal carcinoma is immunogenic and may reasonably be considered as a target for immunotherapy, and attempts to address critical issues and envisage future developments in this challenging research field.
Medical and Health Science
 Abstract

From cancer genomics to cancer immunotherapy: toward second-generation tumor antigens

J Schultze (2001)
Trends in Immunology

Summary

  • The unveiling of the sequence of the human genome, improved bioinformatics tools and optimized immunological analytical tools have made it possible to screen any given protein for immunogenic epitopes.
  • Overexpressed genes in cancer can be identified by gene-expression profiling; immunogenic epitopes can be predicted based on HLA-binding motifs; candidate peptides can be identified by mass spectrometry of tumor-cell-derived HLA molecules; and peptide-specific T cells can be qualitatively and quantitatively analyzed at the single-cell level using ELISPOT and tetramer technologies.
  • We suggest that, based on these advancements, a new class of tumor Ags can be identified by directly linking cancer genomics to cancer immunology and immunotherapy.
Medical and Health Science
 Abstract

Rush Hymenoptera venom immunotherapy: A safe and practical protocol for high-risk patients

G Sturm, et al. (2002)
Journal of Allergy and Clinical Immunology

Summary

  • The aim of this study was to report the 8-year experience with our rush venom immunotherapy regimen in predominantly high-risk patients and to compare data on safety and convenience with the results of 26 studies published from 1978 to 2001.
  • With a rush immunotherapy regimen over a time period of 8 years in predominantly high-risk patients, the incidence of SRs was low, despite the high number of patients with bee venom allergy, who are more likely to have side effects.
  • Epinephrine as rescue medication was never necessary, and the regimen proved to be safe and convenient for both the patients and the medical staff.
Medical and Health Science
 Abstract

Cancer immunotherapy – revisited

WJ Lesterhuis, JBAG Haanen, CJA Punt (2011)
Nature Reviews Drug Discovery

Summary

  • Our insight into antitumour immune responses has increased considerably during the past decades, yet the development of immunotherapy as a treatment modality for cancer has been hampered by several factors.
  • Although durable clinical remissions have been observed with various immunotherapeutic strategies, the percentage of patients who benefited from these interventions has remained too small to justify the general use of such strategies.
  • The recent positive results of clinical trials with novel immunoactive drugs as well as the unexpected finding of a positive interaction between immunotherapy and chemotherapy may herald a new era for the immunotherapy of cancer.
Biology
Medical and Health Science
 Abstract