Home > Treatments > Biological Therapies Show
Biological TherapiesBiological Therapies use or mimic substances that occur naturally in the body to destroy cancer cells. They may be used to stimulate the immune system to fight cancer, control the growth of cancer cells or to overcome side effects of treatment. There are several types of biological therapies. Biological Therapy: "Treatment of diseases with biological materials or biological response modifiers, such as the use of GENES; CELLS; TISSUES; organs; SERUM; VACCINES; and humoral agents." (Source: MeSH) They may also be referred to as 'targeted therapies' or 'biological response modifiers'(BRM) Information for Patients and the PublicInformation for Health Professionals / Researchers Latest Research Publications Angiogenesis Inhibitors Monoclonal Antibodies Cancer Growth Inhibitors Interferon alpha Interleukin 2 (Aldesleukin) Information Patients and the Public (5 links)
Macmillan Cancer
Support Cancer Research UK Oncolink Biological Therapies for CancerNational Cancer
Institute A charitable organization that raises funds for cancer immunology research and provides direct support to cancer scientists through fellowships, grants, and awards. Information for Health Professionals / Researchers (5 links)
ISICR SITC National Cancer Institute Latest Research PublicationsThis list of publications is regularly updated (Source: PubMed). Meng P, Dong QC, Tan GG, et al. BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. Panich
T, Tragoolpua K, Pata S, et al. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) accelerates tumor invasion and metastasis via activation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) expression. The authors were interested in whether the scFv-M6-1B9 intrabody against EMMPRIN that retains EMMPRIN in endoplasmic reticulum could be a potential tool to suppress cervical cancer invasion through inhibition of uPA. The chimeric adenoviral vector Ad5/F35-scFv-M6-1B9 was transferred into human cervical carcinoma HeLa cells to produce the scFv-M6-1B9 intrabody against EMMPRIN. Cell surface expression of EMMPRIN, the membrane-bound uPA, the enzymatic activity of secreted uPA, and the invasion ability were analyzed. The scFv-M6-1B9 intrabody successfully diminished the cell surface expression of EMMPRIN and the membrane-bound uPA on HeLa cells. uPA activity from tissue culture media of EMMPRIN-downregulated HeLa cells was decreased. The invasion ability of HeLa cells harboring scFv-M6-1B9 intrabody was also suppressed. These results suggested that the scFv-M6-1B9 intrabody might represent a potential approach for invasive cervical cancer treatment. The application of scFv-M6-1B9 intrabody in animal experiments and preclinical studies would be investigated further. Tumors are a serious threat to human health. The oncolytic virus is a kind of tumor killer virus which can infect and lyse cancer cells and spread through the tumor, while leaving normal cells largely unharmed. Mathematical models can help us to understand the tumor-virus dynamics and find better treatment strategies. This paper gives a new mathematical model of tumor therapy with oncolytic virus and MEK inhibitor. Stable analysis was given. Because mitogen-activated protein kinase (MEK) can not only lead to greater oncolytic virus infection into cancer cells, but also limit the replication of the virus, in order to provide the best dosage of MEK inhibitors and balance the positive and negative effect of the inhibitors, we put forward an optimal control problem of the inhibitor. The optimal strategies are given by theory and simulation. Vaidakis D, Moustaki I, Zervas I, et
al. The aim of the present study was to identify the sexual behavior, attitudes, beliefs, and knowledge on sexually transmitted infections (STIs) focused on human papilloma virus (HPV) in the Greek adolescent population. The participants were 4547 adolescents, a representative sample for Greek territory with a mean age of 17 years. After written permission from Greek ministry of education each student completed a questionnaire with 36 questions. The fields covered were demographic characteristics, sexual life data, and basic knowledge on HPV. In the present study, 43% and 75% of the participants knew about HPV or cervical cancer, while more than 6 out of 10 did not know the association between the 2. More than 60% of the participants could not answer correctly neither about HPV infection and cervical cancer frequency in sexually active women, nor about protection methods against HPV and cervical cancer. This study shows that the low vaccination coverage of the Greek population may be due to lack of information and awareness of the adolescents and their parents. It is our duty to increase our efforts in order to better educate the population and vaccinate the population as early as possible in their reproductive years. Kroeze SG, Fritz C, Hoyer M,
et al. BACKGROUND AND PURPOSE:
Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. Cohen YC, Zuckerman T, Yeshurun M, et al. We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60-64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m(2) was more frequent in the 60-64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3-4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60-64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60-64. Dlouhy I, Torrente MÁ, Lens S, et al. Diffuse large B cell lymphoma (DLBCL) patients carrying hepatitis C virus (HCV) have higher risk of treatment toxicity and complications. The aim of this study was to assess the impact of HCV in a series of DLBCL patients treated with immunochemotherapy. 321 patients (161 M/160F; median age, 66 years) diagnosed with de novo DLBCL in a single center between 2002 and 2013 were included. Immunodeficiency-related lymphomas were excluded. HCV+ cases were defined by the presence of IgG anti-HCV. Main clinico-biological characteristics and outcome were analyzed according to the viral status. Two hundred ninety patients were HCV- and 31 HCV+. HCV+ patients were older (median age 71 vs. 64 years, P = 0.03), had more often B symptoms (P = 0.013), spleen (P = 0.003), and liver (P = 0.011) involvement, higher rate of early death (<4 months, P = .001), and shorter overall survival (OS). Eleven HCV+ patients had cirrhosis criteria. HCV+ patients with impaired liver function before or during treatment showed inferior OS. Elevated pre-treatment bilirubin correlated also with higher liver toxicity. In a multivariate analysis that included R-IPI score, serum beta2-microglobulin (β2m), HCV status, and presence of cirrhosis, only R-IPI, β2m, and cirrhosis showed independent prognostic impact on OS. The presence of HCV in DLBCL patients entails higher number of complications and early deaths; however, liver impairment and not the hepatitis viral status was the key feature in the outcome of the patients. Brown CE, Alizadeh D, Starr R, et al. A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .). Benyamini N, Avivi I, Dann EJ, et al. Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 10(6)/kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen. Gilli S, Novak U, Taleghani BM, et al. BEAM with BCNU is commonly used for conditioning treatment followed by autologous stem cell transplantation (ASCT). However, pulmonary toxicity and availability issues associated with BCNU prompted us to evaluate bendamustine-replacing BCNU (BeEAM). We analyzed 39 lymphoma patients receiving BeEAM conditioning with 200 mg/m(2) bendamustine at days -7 and -6. The median duration until neutrophil recovery was 11 days, and 15 days for platelet recovery (>20 g/L). The most common grade 3/4 non-hematologic toxicities comprised mucosal side effects (27 pts.). Pulmonary toxicity was observed in one patient (2.5%), and one patient died of septic complications. The CR rate increased from 33% to 74% 100 days after ASCT. After a median follow-up of 18.5 months, progression and death each occurred in 11 patients (28%). Median progression-free and overall survival at 2 years were 69% and 72%. Our data suggest that BeEAM conditioning using bendamustine is safe and results in promising survival rates. Paubelle E, Ducastelle-Leprêtre S,
Labussière-Wallet H, et al. Outcome of patients with primary refractory/relapsed (R/R) acute myeloid leukemia (AML) remains dismal. Herein, we present a retrospective monocentric study of 24 very high-risk AML patients who received a combination of fractionated gemtuzumab ozogamicin (GO) with intermediate-dose cytarabine and daunorubicin as salvage therapy. Median age was 55.3 years. Diagnostic was secondary AML for 33% of them. Seven patients had favorable risk, 8 had intermediate-1 or intermediate-2, and 6 had unfavorable risk of AML according to the European LeukemiaNet prognostic index. Complete remission was achieved in 50% of cases (46% in refractory and 55% in relapsed AML) without excessive toxicity. Thirteen patients could be referred for transplant. Only allogeneic hematopoietic stem cell transplantation provided a benefit in this patient cohort with a 1-year overall survival of 50.7 versus 18.1% in the absence of transplantation. Patients treated with reduced intensity conditioning (RIC) showed a longer survival as compared to those undergoing myeloablative conditioning regimen mainly because of decreased toxicity.Our data suggest that salvage therapy with fractionated GO combined with intermediate-dose cytarabine and daunorubicin in very high-risk patients may serve as a potential bridge therapy to RIC transplant. Suzawa K, Shien K, Peng H, et al. BACKGROUND: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum
stress. Polivka J, Polivka J, Holubec L,
et al. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single anti-angiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed. Quinn EM, Meland E, McGinn S, Anderson
JH BACKGROUND:
Preoperative anaemia is a risk factor for poorer postoperative outcomes and many colorectal cancer patients have iron-deficiency anaemia. The aim of this study was to assess if a preoperative iron-deficiency anaemia management protocol for elective colorectal surgery patients helps improve detection and treatment of iron-deficiency, and improve patient outcomes. Bommareddy PK, Patel A, Hossain S, Kaufman HL Many mammalian viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in tumor cells, the initiation of tumor cell lysis, and the induction of innate and adaptive anti-tumor immunity. Furthermore, viruses can be genetically engineered to reduce pathogenicity and increase immunogenicity resulting in minimally toxic therapeutic agents. Talimogene laherparepvec (T-VEC; Imlygic™), is a genetically modified herpes simplex virus, type 1, and is the first oncolytic virus therapy to be approved for the treatment of advanced melanoma by the US FDA. T-VEC is attenuated by the deletion of the herpes neurovirulence viral genes and enhanced for immunogenicity by the deletion of the viral ICP47 gene. Immunogenicity is further supported by expression of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, which helps promote the priming of T cell responses. T-VEC demonstrated significant improvement in durable response rate, objective response rate, and progression-free survival in a randomized phase III clinical trial for patients with advanced melanoma. This review will discuss the optimal selection of patients for such treatment and describe how therapy is optimally delivered. We will also discuss future directions for oncolytic virus immunotherapy, which will likely include combination T-VEC clinical trials, expansion of T-VEC to other types of non-melanoma skin cancers, and renewed efforts at oncolytic virus drug development with other viruses. Colle R, Cohen R, Cochereau D, et al. Microsatellite instability (MSI) is a tumor phenotype linked to somatic or germline (Lynch syndrome) inactivating alterations of DNA mismatch repair genes. A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer. MSI tumors are characterized by dense immune infiltration and high load of tumor neo-antigens. Growing evidence is accumulating on the efficacy of immune checkpoint inhibition for patients treated for MSI solid tumors. We present a comprehensive overview of MSI phenotype, its biological landscape and current diagnostic methods. Then we focus on MSI as a predictive biomarker of response to immune checkpoint inhibition in the context of colorectal cancer and non-colorectal tumors. Bernier J Besides the local effects of ionizing radiation at the cellular and molecular levels in tumor tissues, the interactions of radiotherapy with the host's immune system are nowadays at the center of many investigations. In some cases, these interactions can be strong enough to immunize the patient against the tumor, leading to a rejection by the host of both the irradiated tumor and distant metastases. In this latter case, the rejection mechanism is called "abscopal effect". Over the last two decades, increasing attention has also been paid to the combination of various forms of immunotherapies with radiation, as an attempt to boost cancer cell killing mechanisms. In particular, a significant number of translational and clinical studies are now investigating both the effects of immune checkpoint blockade strategies and adoptive immunotherapies in combination with radiation. A better understanding of the mechanisms driving the interactions between ionizing radiation and the immune system help us envision the advantages that may be offered by the adjunction of immunotherapy to radiotherapy in various clinical models. McArthur HL, Page DB Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers. Specifically, overall response rates of 19% with PD-1/PD-L1-directed antibodies have been reported in 2 small studies of women with PD-L1-positive, heavily pretreated advanced triple-negative breast cancer. In combination with nab-paclitaxel, confirmed response rates were 46% in a PD-L1-unselected population in the first-line metastatic triple-negative breast cancer setting. Checkpoint-blocking antibodies also have been evaluated in small studies of women with hormone receptor-positive metastatic breast cancer, and in women whose breast cancers lack PD-L1 expression, with more modest response rates. It has been hypothesized that some breast cancers are not inherently recognized by the immune system; however, preclinical and preliminary clinical data suggest that inherently modest immunogenicity may be overcome with novel vaccination strategies, as well as strategies that combine immune checkpoint blockade with methods of optimizing antigen presentation, such as tumor ablation, radiation, chemotherapy, or other approaches. If ongoing registrational trials support the use of immunotherapy, it could revolutionize the care of early-stage and metastatic breast cancer, and ideally improve cure rates. Davila ML, Brentjens RJ Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable. CD19-targeted CAR T cells have induced complete remissions of disease in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), who have an expected complete response rate of 30% in response to chemotherapy. The high efficacy of CAR T cells in B-ALL suggests that regulatory approval of this therapy for this routinely fatal leukemia is on the horizon. We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B-ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed. Zhao W, Zhang Y, Jiang X, Cui C Small interfering RNA (siRNA) delivery is a prospective method in gene therapy, but it has application limitations such as negative charge, water solubility and high molecular weight. In this study, a safe and efficient nano-vector, CRS, was designed and synthesized to facilitate siRNA delivery. Physical and chemical properties of VEGF-siRNA/CRS were characterized by methods including scanning electron microscopy (SEM), transmission electron microscopy, zeta potential (ζ) measurement, drug-releasing rate measurement, gel electrophoresis and confocal microscopy. The biological activities were evaluated using cell viability assay, gene-silencing efficacy assay in vitro, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and antitumor tests in vivo. The mean nanoparticle size of VEGF-siRNA/CRS was 121.4±0.3 nm with positive ζ potential of 7.69±4.47 mV. The release rate of VEGF-siRNA from VEGF-siRNA/CRS was 82.50% sustained for 48 h in Tris-ethylenediaminetetraacetic acid buffer (pH 8.0). Real-time polymerase chain reaction was used to analyze the efficiency of the transfection, and the result showed that VEGF mRNA expression had been knocked down by 82.36%. The expression of VEGF protein was also recorded to be downregulated to 14.83% using ELISA. The results of cytotoxicity measured by Cell Counting Kit-8 assay showed that VEGF-siRNA/CRS had significant inhibitory effect on HeLa cells. The results of antitumor assays indicated that VEGF-siRNA/CRS exhibited tumor cell growth inhibition in vivo. The results demonstrated that VEGF-siRNA could be delivered and transported by the designed carrier, while siRNA could be released constantly and led to an increasing gene-silencing effect against VEGF gene. In conclusion, VEGF-siRNA/CRS is a promising carrier for siRNA delivery, and further studies are warranted. Atretkhany KN, Drutskaya MS Myeloid-derived suppressor cells represent a heterogeneous population of immature myeloid cells. Under normal conditions, these cells differentiate into macrophages, dendritic cells, and granulocytes. However, in pathological states such as inflammation, infection, or tumor growth, there is an arrest of their differentiation that results in the accumulation of immature myeloid cells in the organism. In addition, these cells acquire a suppressor phenotype, expressing anti-inflammatory cytokines and reactive oxygen and nitrogen species, and suppress T-cell immune response. Myeloid-derived suppressor cells (MDSC) contribute to cancerogenesis by forming a favorable microenvironment for tumor growth. Proinflammatory cytokines, secreted by tumor cells and the tumor microenvironment, induce angiogenesis and metastasis and promote tumor growth. They also provide signals necessary for survival, accumulation, and function of MDSC. Understanding the mechanisms of myeloid suppressor cell development and the use of proinflammatory cytokine inhibitors may prove beneficial for tumor therapy. Holtick U, Herling M, Pflug N, et al. The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol. We retrospectively analyzed 130 consecutive patients with high-risk or relapsed AML after aSCT following FLAMSA conditioning at our center. Fifty-eight patients were treated with FLAMSA/treosulfan due to age and/or comorbidities. Seventy-two patients were treated with FLAMSA/TBI. Median age of patients treated with FLAMSA/treosulfan was 60 years compared to 46 years in those treated with FLAMSA/TBI. The cumulative incidence of a non-relapse mortality at 4 years was 28% in FLAMSA/treosulfan patients as compared to 13% in FLAMSA/TBI. Cumulative incidence of relapse was higher in patients treated with FLAMSA/TBI (46 vs. 32%). This difference was even more prominent for patients treated in blast persistence prior to transplant (relapse incidence 70% for TBI vs. 35% for treosulfan). The overall and relapse-free survival rates at 4 years were 47 and 41%, respectively, for patients treated with FLAMSA/TBI as compared to 43 and 40% in patients treated with FLAMSA/treosulfan. These data indicate an anti-leukemic activity by FLAMSA/treosulfan especially in patients with a blast persistence prior to transplant. Older age was an independent factor for a higher non-relapse mortality. Translating FLAMSA/treosulfan to younger patients, a lower non-relapse mortality, and an improved anti-leukemic activity might add up to improved overall survival. Randomized studies are required to demonstrate an improved efficacy of treosulfan- versus TBI-based FLAMSA conditioning. Kim S, Chung HW, Kong HY, Lim JB PURPOSE: To identify new immunogenic HLA-A*33;03-restricted epitopes from the human papillomavirus (HPV) 16 E7 protein for immunotherapy against cervical cancer. Paulino Pereira NR, Langerhuizen DW, Janssen SJ, et al. BACKGROUND AND OBJECTIVES: We assessed whether allogeneic blood transfusions were associated with infection-within 90 days-after surgery for bone metastatic disease. Furthermore, we
assessed other risk factors associated with infection. Yamasaki S, Hirakawa A, Aoki J, et al. Reduced-intensity conditioning (RIC) regimens extend the therapeutic use of allogeneic hematopoietic cell transplantation (HCT) to older patients. The survival trend in 2325 patients aged >50 years presenting with de novo acute myeloid leukemia (AML) who underwent first reduced-intensity HCT (RIC-HCT) was assessed by retrospectively analyzing outcomes between 2000 and 2013. The annual number of RIC-HCTs in Japan was higher in the 2008-2013 period (n = 205/year [1229/6 years]) than in the 2000-2007 period (n = 137/year [1096/8 years]). Overall and disease-free survival were higher in the 2008-2013 period (P < 0.001) because of the improvement in transplant-related mortality (TRM). Survival regarding RIC-HCT for AML has improved over time, with an increased number of RIC-HCTs in patients with a Karnofsky performance status (KPS) ≥80. However, TRM remains high and the relapse rate has not improved over time. Multivariate analyses showed that a KPS ≥80 and complete remission at HCT were associated with less TRM and relapse, and better survival regardless of age ≥65 years. Accurate timing and prospective identification of patients at risk of TRM may aid the development of risk-adapted strategies for RIC-HCT in AML patients regardless of age. Cheng L, Ke Y, Yu S, Jing J To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy. Doxorubicin (DOX) and pHSP70-Plk1-shRNA were included in the targeted thermosensitive co-delivery system, and in vitro DOX release activity, targeted gene silencing efficiency and in vitro antitumor efficacy were investigated. The results showed that the optimal culture conditions of MTB AMB-1 are an oxygen concentration of 4.0%, a pH value of 7.0, 20 μmol/L of ferrous sulfate, 800 mg/L of sodium nitrate, and 200 mg/L of succinic acid. The temperature of BMs reached 43°C within 3 minutes and could be maintained for 30 minutes by adjusting the magnitude of the alternating magnetic field (AMF). The diameters of BMs, BM-DOX, BM-recombinant eukaryotic plasmid pHSP70-Plk1-shRNA (shPlk1), and BM-DOX-shPlk1 were 43.7±4.6, 79.2±5.4, 88.9±7.8, and 133.5±11.4 nm, respectively. The zeta potentials of BMs, BM-DOX, BM-shPlk1, and BM-DOX-shPlk1 were -29.4±6.9, -9.5±5.6, -16.7±4.8, and -10.3±3.1 mV, respectively. Besides, the system exhibited good release behavior. DOX release rate from BM-DOX-shPlk1 was 54% after incubation with phosphate-buffered saline at 43°C and 37% after incubation with 50% fetal bovine serum, which was significantly higher than that at 37°C (P<0.05). In addition, the expressions of Plk1 mRNA and protein were significantly suppressed in cells treated with BM-DOX-shPlk1 following hyperthermia treatment under the influence of an AMF compared to other groups (P<0.05). Furthermore, evaluation of the effect of in vitro antitumor revealed that BM-DOX-shPlk1 following hyperthermia treatment under the influence of an AMF was significantly more effective than others in tumor inhibition. In conclusion, the new heat-sensitive co-delivery system represents a promising approach for the treatment of cancer. Santana-Davila R, Bhatia S, Chow LQ Importance: There are at least 7 viruses implicated in the pathogenesis of 10% to 15% of all human cancers worldwide. Despite a high prevalence of infection with these viruses, only a minority of infected individuals develop a subsequent malignant tumor, underscoring the important role that host and
environmental factors have in cancer development. This article reviews the mechanisms of viral carcinogenesis, with an emphasis on the viral evasion of the host immune system, and discusses how to harness the immune system effectively as a therapeutic tool in select cancers. Winkelmann N, Desole M, Hilgendorf I, et al. INTRODUCTION: Even in the era of proteasome inhibitors and immunomodulatory drugs, the autologous stem cell transplantation after high-dose melphalan continues to represent a standard
approach for myeloma patients in first-line therapy. Different mobilization chemotherapies before stem cell apheresis have been published while cyclophosphamide at a dose level of up to 4 g/m(2) has been evaluated and is commonly applied. In contrast, lower dose levels of cyclophosphamide (e.g., 1.5 g/m(2)) did not result in a sufficient collection of stem cells. Holubova M, Miklikova M, Leba M, et al. BACKGROUND: Leukaemia is an aggressive cancer of haematopoiesis. Despite increasing treatment success, the relapse rate is still high. Natural killer (NK) cells play a key role in the immune response to malignancies; thus, it is conceivable that NK cell-based immunotherapy may control relapses, while
extending the disease-free survival. In our study, we investigated whether cryopreserved NK cells are able to kill the leukaemic K562 cell line, the necessity of IL-2 co-application and the association of activation marker expression (NKp44, NKG2D and CD25) with cytotoxic potential. Suehiro Y Adult T-cell leukemia/lymphoma (ATL) is a HTLV-1 induced T-cell malignancy with an extremely poor prognosis. There is a long latency period between HTLV-1 infection and the onset of ATL, which indicates the existence of multistep mechanisms of leukemogenesis in the infected cells. Tax, which is encoded by the HTLV-1 pX region, plays a crucial role in HTLV-1 leukemogenesis and is a major target of CTL. We developed an anti-ATL therapeutic vaccine consisting of autologous dendritic cells that is pulsed with Tax peptides (Tax-DC). The vaccination protocol was completed with three injections at a 2-week interval, within one month. Good quality of life and long-term treatment-free survival were observed for more than 3 years in two of the three patients enrolled in the pilot study. Furthermore, the proviral load remained mostly around the carrier level, with minor fluctuation, after vaccination. Tax-specific proliferative CTL responses were observed in all cases and sporadically augmented responses were also subsequently detected. The Tax-DC vaccine might be a well-tolerated and long-lasting maintenance therapy that is acceptable even for elderly patients. Based on the encouraging results, we are now conducting a clinical trial of Tax-DC vaccine combined with anti-CCR4 antibody to enhance the efficacy of the vaccine as next-generation immunotherapy. What are the different types of biological therapies?Types of biological therapy include immunotherapy (such as cytokines, cancer treatment vaccines, and some antibodies) and some targeted therapies. Also called biological response modifier therapy, biotherapy, and BRM therapy.
What are biological treatments in psychology?any form of treatment for mental disorders that attempts to alter physiological functioning, including drug therapies, electroconvulsive therapy, and psychosurgery.
What is the most common form of biological therapy?Monoclonal antibodies are a common type of biological therapy for many different cancers and other conditions. These are laboratory-produced antibodies that are designed to attack specific proteins expressed by abnormal cells.
What are biochemical therapies?Biochemical therapy may be defined as “correction of innate or acquired chemical imbalances using amino acids, vitamins, minerals, and other biochemicals naturally present in the body.” In this study, diagnoses of chemical imbalances were based on chemical analyses of dozens of key biochemicals in blood, urine, and ...
|