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1.
Successful treatment of cancer patients with a combination of monoclonal antibodies (mAb) and chemotherapeutic drugs has spawned
various other forms of additional combination therapies, including vaccines or adoptive lymphocyte transfer combined with
chemotherapeutics. These therapies were effective against established tumors in animal models and showed promising results
in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. Although combination
between immunotherapy and chemotherapy has long been viewed as incompatible as chemotherapy, especially in high doses meant
to increase anti-tumor efficacy, has induced immunosuppression, various mechanisms may explain the reported synergistic effects
of the two types of therapies. Thus direct effects of chemotherapy on tumor or host environment, such as induction of tumor
cell death, elimination of regulatory T cells, and/or enhancement of tumor cell sensitivity to lysis by CTL may account for
enhancement of immunotherapy by chemotherapy. Furthermore, induction of lymphopenia by chemotherapy has increased the efficacy
of adoptive lymphocyte transfer in cancer patients. On the other hand, immunotherapy may directly modulate the tumor’s sensitivity
to chemotherapy. Thus, anti-tumor mAb can increase the sensitivity of tumor cells to chemotherapeutic drugs and patients treated
first with immunotherapy followed by chemotherapy showed higher clinical response rates than patients that had received chemotherapy
alone. In conclusion, combination of active specific immunotherapy or adoptive mAb or lymphocyte immunotherapy with chemotherapy
has great potential for the treatment of cancer patients which needs to be confirmed in larger controlled and randomized Phase
III trials. 相似文献
2.
Arnaud Morel Nadine Fernandez A. de La Coste Hédi Haddada Mireille Viguier Barbara S. Polla Bénédicte Antoine A. Kahn 《Cancer immunology, immunotherapy : CII》1998,46(5):277-282
The use of gene-modified tumor cells as a strategy for active immunotherapy is currently undergoing intensive fundamental
and clinical research. Most clinical trials use γ-ray-irradiated tumor cells as vaccine, although little is known about the
effects of irradiation on the immunogenicity of tumor cells. In particular, no data have been reported so far concerning the
effects of γ-ray irradiation on the expression of B7 molecules in tumor cells. In this paper, we show a neoexpression of the
B7.1 molecule after γ-ray irradiation in tumor cell lines from different tissues, while the B7.2 molecule remains unexpressed
in all the cell lines tested. Furthermore, the induction of B7.1 molecule membrane expression after irradiation is shown to
result from the neoexpression of B7.1 mRNA, and to be reproduced with H2O2 oxidative stress. These data could explain the enhanced immunogenicity of many tumor cells after irradiation, and could lead
to new immunotherapy protocols.
Received: 27 November 1997 / Accepted: 26 February 1998 相似文献
3.
Rosalind A. Graham J. M. Burchell J. Taylor-Papadimitriou 《Cancer immunology, immunotherapy : CII》1996,42(2):71-80
The identification and cloning of several tumour antigens together with an improvement in the understanding of the mechanisms
involved in antigen presentation and immune recognition has opened up the possibility of using active specific immunotherapy
as a treatment for certain cancers. This review discusses the tumour-associated MUC1 gene product of the polymorphic epithelial mucin (PEM), as a potential target molecule for cancer treatment. PEM is both
over-expressed and aberrantly glycosylated in many carcinomas resulting in an antigenically distinct molecule. Furthermore,
immune responses specific for PEM have been detected in cancer patients. Both syngeneic and transgenic murine model systems
have been developed in order to compare the efficacy and toxicity of various PEM-based immunogens in tumour rejection studies,
and to further improve the understanding of antigen presentation and the mechanisms underlying tumour rejection. Such models
also allow the examination of MUC1-based immunogens as a treatment for existing tumours. Clinical trials in progress using
immunogens based on the MUC1 gene product are briefly discussed.
Received: 23 November 1995 / Accepted: 4 January 1996 相似文献
4.
Karavidas MK Tsai PS Yucha C McGrady A Lehrer PM 《Applied psychophysiology and biofeedback》2006,31(3):203-216
The clinical presentation of primary Raynaud’s phenomenon (RP) derives from various pathogenic triggers. The use of thermal biofeedback (TBF) may be of benefit in reducing the severity and frequency of attacks. This article summarizes the relevant research regarding the pathophysiology of primary RP and mechanism of TBF for RP. Systematic reviews of the efficacy of TBF for RP and treatment guidelines for clinicians are provided. The panel concludes that the level of evidence for TBF efficacy is categorized as Level IV: efficacious. The rationale, based on three randomized controlled trials conducted in independent laboratories, demonstrated “superiority or equivalence” of treatments that include TBF. However, randomly controlled trials (RCT) with positive clinical outcomes tended to be small. A large RCT with negative results did not effectively teach handwarming skills. Procedures for reviewing and rating of the levels of evidence of efficacy of studies was based on the Template for Developing Guidelines for the Evaluation of the Clinical Efficacy of Psychophysiological Interventions developed by the joint task force of the AAPB and the Society for Neuronal Regulation (SNR). 相似文献
5.
Immunogenic HER-2/neu peptides as tumor vaccines 总被引:6,自引:0,他引:6
Baxevanis CN Sotiriadou NN Gritzapis AD Sotiropoulou PA Perez SA Cacoullos NT Papamichail M 《Cancer immunology, immunotherapy : CII》2006,55(1):85-95
During the last decade, a large number of tumor-associated antigens (TAA) have been identified, which can be recognized by
T cells. This has led to renewed interest in the use of active immunization as a modality for the treatment of cancer. HER-2/neu
is a 185-KDa receptor-like glycoprotein that is overexpressed by a variety of tumors including breast, ovarian, lung, prostate
and colorectal carcinomata. Several immunogenic HER-2/neu peptides recognized by cytotoxic T lymphocytes (CTL) or helper T
lymphocytes (TH) have been identified thus far. Patients with HER-2/neu over-expressing cancers exhibit increased frequencies
of peripheral blood T cells recognizing immunogenic HER-2/neu peptides. Various protocols for generating T cell-mediated immune
responses specific for HER-2/neu peptides have been examined in pre-clinical models or in clinical trials. Vaccination studies
in animals utilizing HER-2/neu peptides have been successful in eliminating tumor growth. In humans, however, although immunological
responses have been detected against the peptides used for vaccination, no clinical responses have been described. Because
HER-2/neu is a self-antigen, functional immune responses against it may be limited through tolerance mechanisms. Therefore,
it would be interesting to determine whether abrogation of tolerance to HER-2/neu using appropriate adjuvants and/or peptide
analogs may lead to the development of immune responses to HER-2/neu epitopes that can be of relevance to cancer immunotherapy.
Vaccine preparations containing mixtures of HER-2/neu peptides and peptide from other tumor-related antigens might also enhance
efficacy of therapeutic vaccination.
This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2004 (PIVAC 4)”, held in Freudenstadt-Lauterbad,
Black Forest, Germany, on 22–25 September 2004 相似文献
6.
Therapeutic cancer vaccines are an emerging and potentially effective treatment modality. Cancer vaccines are usually very
well tolerated, with minimal toxicity compared with chemotherapy. Unlike conventional cytotoxic therapies, immunotherapy does
not result in immediate tumor shrinkage but may alter growth rate and thus prolong survival. Multiple randomized controlled
trials of various immunotherapeutic agents have shown a delayed separation in Kaplan–Meier survival curves, with no evidence
of clinical benefit within the first 6–12 months of vaccine treatment. Overall survival benefit is seen in patients with lower
disease burden who are not expected to die within those initial 6–12 months. The concept of improved overall survival without
marked initial tumor reduction represents a significant shift from the current paradigms established by standard cytotoxic
therapies. Future clinical studies of therapeutic vaccines should enroll patients with either lower tumor burden, more indolent
disease or both, and must seek to identify early markers of clinical benefit that may correlate with survival. Until then,
improved overall survival is the only clear, discriminatory endpoint for therapeutic vaccines as monotherapies. 相似文献
7.
Bernardo R Tura Helena F Martino Luis H Gowdak Ricardo Ribeiro dos Santos Hans F Dohmann José E Krieger Gilson Feitosa Fábio Vilas-Boas Sérgio A Oliveira Suzana A Silva Augusto Z Bozza Radovan Borojevic Antonio C Campos de Carvalho 《Trials》2007,8(1):1-4
Background
Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials.Method/Design
We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group.Discussion
Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388). 相似文献8.
Ferrantini M Capone I Marincola FM Parmiani G Belardelli F 《Cancer immunology, immunotherapy : CII》2007,56(4):581-585
The main aims of the international meeting “Immunotherapy of Cancer: Challenges and Needs” were to review the state of the
art of cancer immunotherapy and to identify critical issues which deserve special attention for promoting progress of research
in this field, with a particular focus on the perspectives of clinical research. Novel concepts and strategies for identifying,
monitoring and predicting effective responses to cancer immunotherapy protocols were presented, focused on the use of adjuvants
(CpG oligonucleotides) or cytokines (IFN-alpha) to enhance the efficacy of cancer vaccines. Moreover, the possible advantages
of using different types of dendritic cells (for active immunization strategies) or T cells (for adoptive immunotherapy protocols)
were debated. A consensus was achieved on the need for enhancing the efficacy of cancer vaccines or adoptive cell immunotherapy by combining these
strategies with other anti-cancer treatments, including chemotherapy. Finally, initiatives for promoting clinical research
by establishing a strategic cooperation in the field of cancer immunotherapy based on the active participation of all the
relevant actors, including public institutions responsible of Public Health, National Cancer Institutes, industry, representatives
of regulatory bodies, and patients’ organizations were proposed. 相似文献
9.
Background
Although allergen specific immunotherapy (SIT) represents the only immune- modifying and curative option available for patients with allergic rhinitis (AR), the optimal schedule for specific subcutaneous immunotherapy (SCIT) is still unknown. The objective of this study is to systematically assess the efficacy and safety of cluster SCIT for patients with AR.Methods
By searching PubMed, EMBASE and the Cochrane clinical trials database from 1980 through May 10th, 2013, we collected and analyzed the randomized controlled trials (RCTs) of cluster SCIT to assess its efficacy and safety.Results
Eight trials involving 567 participants were included in this systematic review. Our meta-analysis showed that cluster SCIT have similar effect in reduction of both rhinitis symptoms and the requirement for anti-allergic medication compared with conventional SCIT, but when comparing cluster SCIT with placebo, no statistic significance were found in reduction of symptom scores or medication scores. Some caution is required in this interpretation as there was significant heterogeneity between studies. Data relating to Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in 3 included studies were analyzed, which consistently point to the efficacy of cluster SCIT in improving quality of life compared to placebo. To assess the safety of cluster SCIT, meta-analysis showed that no differences existed in the incidence of either local adverse reaction or systemic adverse reaction between the cluster group and control group.Conclusion
Based on the current limited evidence, we still could not conclude affirmatively that cluster SCIT was a safe and efficacious option for the treatment of AR patients. Further large-scale, well-designed RCTs on this topic are still needed. 相似文献10.
H Kusnierczyk E Pajtasz-Piasecka C Radzikowski 《Cancer immunology, immunotherapy : CII》1999,16(4):267-278
The therapeutic efficacies of two chemical agents—cyclophosphamide (CY) and compound CBM-11—were compared in a chemo-immunotherapy
protocol combining a single injection of a cytotoxic agent with a series of weekly peritumoural (p.t.) administrations of
nontumourigenic plasmocytoma cells engineered to produce interleukin-2 (IL-2). Compound CBM-11, an optically active S(−) isomeric
form of a bromine-substituted analogue of ifosfamide, is currently used in Phase I clinical trials in Poland. The treatment
was applied to mice bearing well-established subcutaneous (s.c.) MC-38 colon tumours. Single intraperitoneal injection of
200 mg/kg of CY or of an equitoxic dose of 140 mg/kg of CBM-11 alone resulted in a tumour growth delay (TGD) of 10–13 and
17–21 d, respectively. This effect was accompanied by an increase in life-span (ILS) of at most 42 and 62% over control. Complete
responses (CR) were not observed. Combination of CY or CBM-11 with 6–7 p.t. injections of IL-2-secreting cells resulted in
potentiation of the therapeutic effects: TGD and ILS values were considerably increased and long-lasting CRs were observed.
The overall incidence of CR after combined treatment was ca 16% and 42% for CY and CBM-11, respectively (P=0.049). A specific anti-MC-38 immunity was induced by the treatment, as verified by rechallenge of cured mice with MC-38
tumour cells 3–4 months post therapy cessation. Our results indicate that tumour destruction by chemotherapy (even if not
complete) and prolonged local delivery of IL-2 secreted by allogeneic cells of an easy to culture line are sufficient to secure
long-lasting specific antitumour immunity in cured mice. 相似文献
11.
Oba K Teramukai S Kobayashi M Matsui T Kodera Y Sakamoto J 《Cancer immunology, immunotherapy : CII》2007,56(6):905-911
Non-specific immunopotentiators, such as polysaccharide K (PSK), also known as OK-432, induce anti-tumor effects via immunological
responses. The efficacy of combination immunochemotherapy using these immunopotentiators has been examined by multiple previous
studies. The survival benefits of immunochemotherapy for patients with curative resections of gastric cancers are not widely
accepted. To clarify this issue, we performed a meta-analysis to evaluate the effect of immunochemotherapy on survival in
patients with curative resections of gastric cancer. For this study, we compared the results of chemotherapy and immunotherapy
using the biological response modifier PSK as an immunopotentiator. The meta-analysis included 8,009 patients from eight randomized
controlled trials after central randomization. The overall hazard ratio for eligible patients was 0.88 (95% confidence interval,
0.79–0.98; P = 0.018) with no significant heterogeneity [χ
2(8) for heterogeneity = 11.7; P = 0.16]. The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK improves the survival of patients
after curative gastric cancer resection. 相似文献
12.
Anti-idiotype cancer vaccines: past and future 总被引:2,自引:0,他引:2
D. Herlyn Rajasekharan Somasundaram Weiping Li Haruhiko Maruyama 《Cancer immunology, immunotherapy : CII》1996,43(2):65-76
Anti-idiotypic antibodies (Ab2) binding to the antigen-combining site of antitumor antibodies (Ab1) can induce anti-anti-idiotypic
antibodies (Ab3) that specifically bind to the tumor antigen recognized by Ab1. Furthermore, Ab2, mimicking tumor antigens,
have been shown to induce anti-anti-idiotypic proliferative T lymphocytes of the helper and suppressor type, as well as cytotoxic
lymphocytes. The immunomodulatory activities of Ab2 have been demonstrated both in animals and in patients. The demonstration
of tumor growth inhibition by anti-idiotypes in preclinical and phase I clinical studies emphasizes that randomized control
trials should be performed to demonstrate clinical efficacy of Ab2 vaccines.
Received: 25 July 1996 / Accepted: 22 August 1996 相似文献
13.
Oncolytic virus immunotherapy is rapidly gaining interest in the field of immunotherapy against cancer. The minimal toxicity upon treatment and the dual activity of direct oncolysis and immune activation make therapy with oncolytic viruses (OVs) an interesting treatment modality. The safety and efficacy of several OVs have been assessed in clinical trials and, so far, the Food and Drug Administration (FDA) has approved one OV. Unfortunately, most treatments with OVs have shown suboptimal responses in clinical trials, while they appeared more promising in preclinical studies, with tumours reducing after immune cell influx. In several clinical trials with OVs, parameters such as virus replication, virus-specific antibodies, systemic immune responses, immune cell influx into tumours and tumour-specific antibodies have been studied as predictors or correlates of therapy efficacy. In this review, these studies are summarized to improve our understanding of the determinants of the efficacy of OV therapies in humans and to provide insights for future developments in the viro-immunotherapy treatment field. 相似文献
14.
Annabelle Grolleau-Julius Lisa Abernathy Erin Harning Raymond L. Yung 《Cancer immunology, immunotherapy : CII》2009,58(12):1935-1939
Effective cancer immunotherapy depends on the body’s ability to generate tumor antigen-presenting cells and tumor-reactive
effector lymphocytes. As the most potent antigen presenting cells (APCs), dendritic cells (DCs) are capable of sensitizing
T cells to new and recall antigens. Clinical trials of antigen-pulsed autologous DCs have been conducted in patients with
a number of hematological and solid cancers, including malignant melanoma, lymphoma, myeloma, and non-small cell lung cancer.
These studies suggest that antigen-loaded DC vaccination is a potentially safe and effective cancer therapy. However, the
clinical results have been variable. Since the elderly are preferentially affected by diseases targeted by DC-directed immunotherapy,
it is quite striking that few studies to date have focused on the effect of aging on DC function, a key aspect of optimal
immunotherapy design in an aging population. In the present paper, we will discuss the consequences of aging on murine bone
marrow-derived DC function and their use in cancer immunotherapy. 相似文献
15.
OBJECTIVE: To systematically review the benefits and risks associated with the use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1998 that described randomized controlled trials of benzodiazepines for the treatment of insomnia. Key words included "benzodiazepines" (exploded), "randomized controlled trial" and "insomnia." Bibliographies of relevant articles were reviewed for additional studies and manufacturers of benzodiazepines were asked to submit additional randomized controlled trial reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were randomized controlled trials involving patients with insomnia and compared a benzodiazepine with placebo or another active agent. Of the 89 trials originally identified, 45 met our criteria, representing a total of 2672 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records indicated that, when compared with placebo, benzodiazepines decreased sleep latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7 to 9.2) and significantly increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep latency; those randomized to benzodiazepine treatment estimated a sleep latency decrease of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving benzodiazepine treatment reported adverse effects, especially daytime drowsiness and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to 2.4), dropout rates for the benzodiazepine and placebo groups were similar. Cognitive function decline including memory impairment was reported in several of the studies. Zopiclone was not found to be superior to benzodiazepines on any of the outcome measures examined. INTERPRETATION: The use of benzodiazepines in the treatment of insomnia is associated with an increase in sleep duration, but this is countered by a number of adverse effects. Additional studies evaluating the efficacy of nonpharmacological interventions would be valuable. 相似文献
16.
M. T. Scott 《Cancer immunology, immunotherapy : CII》1979,6(2):107-112
Summary A CBA mouse fibrosarcoma (M4) growing as a solid tumour was treated with a single high dose (200 mg/kg) of cyclophosphamide (CY) followed by C. parvum (CP) immunotherapy. The optimal time for the administration of both nonspecific (CP IV) and active specific (SC CP-irradiated tumour cell mixtures) immunotherapy after CY was 4 days, compared with 1, 8, or 12 days. Optimal combinations of CY and CP were synergistic in that they provided a stronger antitumour effect than the sum of the individual effects of the two agents. In keeping with the finding that a 4-day interval between CY and CP was better than only 1 day, studies in normal mice show that when CP is given early during the suppressive phase of CY the onset of both specific and nonspecific antitumour effects are delayed. CY increased the susceptibility of mice to the toxic effects of a subsequent high systemic dose of CP. 相似文献
17.
Bear HD Roberts J Cornell D Tombes MB Kyle B 《Cancer immunology, immunotherapy : CII》2001,50(5):269-274
Adoptive immunotherapy (AIT) of cancer with T lymphocytes may be limited by the need to activate tumor antigen-sensitized
cells in vitro. In murine models, we have shown that AIT with tumor-sensitized T cells that have been pharmacologically activated
with bryostatin 1 and ionomycin plus interleukin-2 can induce tumor regression. A Phase I clinical trial was carried out to
assess the feasibility and toxicity associated with using tumor- or vaccine-draining lymph node cells, activated pharmacologically
and expanded in culture with low-dose interleukin-2 and infused intravenously, followed by IL-2 infusion. Nine patients were
entered into the trial, and six were treated as planned. Average expansion of cell numbers over 13 to 27 days in culture was
118-fold. No patient's cells reached the target cell number (2.5 × 1010). Infusion of these cells did not result in any unexpected toxicities. The toxicities observed were related to IL-2 infusion,
and conformed to the expected range of side-effects. Based on these Phase I results, additional trials, with tumor antigen
vaccine-sensitized DLN and technical modifications of the culture technique, are planned.
Received: 18 January 2001 / Accepted: 26 April 2001 相似文献
18.
Ahui Fan Boda Wang Xin Wang Yongzhan Nie Daiming Fan Xiaodi Zhao Yuanyuan Lu 《International journal of biological sciences》2021,17(14):3837
Following dramatic success in many types of advanced solid tumors, interest in immunotherapy for the treatment of colorectal cancer (CRC) is increasingly growing. Given the compelling long-term durable remission, two programmed cell death 1 (PD-1)-blocking antibodies, pembrolizumab and nivolumab (with or without Ipilimumab), have been approved for the treatment of patients with metastatic colorectal cancer (mCRC) that is mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). Practice-changing results of several randomized controlled trials to move immunotherapy into the first-line treatment for MSI-H metastasis cancer and earlier stage were reported successively in the past 2 years. Besides, new intriguing advances to expand the efficacy of immunotherapy to mCRC that is mismatch-repair-proficient and low microsatellite instability (pMMR-MSI-L) demonstrated the potential benefits for the vast majority of mCRC cases. Great attention is also paid to the advances in cancer vaccines and adoptive cell therapy (ACT). In this review, we summarize the above progresses, and also highlight the current predictive biomarkers of responsiveness in immunotherapy with broad clinical utility. 相似文献
19.
Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials. This review summarized recent development in clinical trials of PD-1 and PD-L1 antibodies for cancer immunotherapy. 相似文献
20.
Bo Xiong Chunbin Wang Yuanqing Yao Yuwen Huang Jie Tan Yin Cao Yanke Zou Jing Huang 《PloS one》2015,10(6)