Skip to main content

Home/ Dr. Goodyear/ Group items tagged immunotherapy cancer

Rss Feed Group items tagged

Nathan Goodyear

Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside - 0 views

  • MAF precursor activity has also been lost or reduced after Gc-globulin treatment in some cancer cell lines
  • This appears to result from the deglycosylated ɑ-N-acetylgalactosaminidase (nagalase) secreted from cancerous cells
  • Nagalase has been detected in many cancer patients, but not in healthy individuals
  • ...31 more annotations...
  • Studies have shown that the production of nagalase has a mutual relationship with Gc-MAF level and immunosuppression
  • It has been demonstrated that serum levels of nagalase are good prognosticators of some types of cancer
  • The nagalase level in serum correlates with tumor burden and it has been shown that Gc-MAF therapy progresses, nagalase activity decreases
  • It has been shown that Gc-MAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1
  • The effect of Gc-MAF on chemotaxis or activation of tumoricidal macrophages is likely the main mechanism against angiogenesis.
  • Administration of Gc-MAF stimulates immune-cell progenitors for extensive mitogenesis, activates macrophages and produces antibodies. “This indicates that Gc-MAF is a powerful adjuvant for immunization.”
  • Cancer cell lines do not develop into tumor genes in mouse models after Gc-MAF-primed immunization (29-31) and the effect of Gc-MAF has been approved for macrophage stimulation for angiogenesis, proliferation, migration and metastatic inhibition on tumors induced by MCF-7 human breast cancer cell line
  • The protocol included: "a high dose of second-generation Gc-MAF (0.5 ml) administered twice a week intramuscularly for a total of 21 injections.”
  • Yamamoto et al. showed that the administration of Gc-MAF to 16 patients with prostate cancer led to improvements in all patients without recurrence
  • Inui et al. reported that a 74-year-old man diagnosed with prostate cancer with multiple bone metastases was in complete remission nine months after initiation of GcMAF therapy simultaneously with hyper T/NK cell, high-dose vitamin C and alpha lipoic acid therapy
  • It has also been approved for non-neoplastic diseases such as autism (41), multiple sclerosis (42, 43), chronic fatigue syndrome (CFS) (40), juvenile osteoporosis (44) and systemic lupus erythematous (45).
  • Gc-MAF has been verified for use in colon, thyroid (38), lung (39), liver, thymus (36), pancreatic (40), bladder and ovarian cancer and tongue squamous carcinoma
  • Prostate, breast, colon, liver, stomach, lung (including mesothelioma), kidney, bladder, uterus, ovarian, head/neck and brain cancers, fibrosarcomas and melanomas are the types of cancer tested thus far
  • weekly administration of 100 ng Gc-MAF to cancer at different stages and types showed curative effects at different follow-up times
  • this treatment has been suggested for non-anemic patients
  • Studies have shown that weekly administration of 100 ng Gc-MAF to cancer patients had curative effects on a variety of cancers
  • Because the half-life of the activated macrophages is approximately one week, it must be administered weekly
  • In vivo weekly intramuscular administration of Gc-MAF (100 ng) for 16-22 weeks was used to treat patients with breast cancer
  • individuals harboring different VDR genotypes had different responses to Gc-MAF and that some genotypes were more responsive than others
  • Administration of Gc-MAF for cancer patients exclusively activates macrophages as an important cell in adaptive immunity
  • Gc-MAF supports humoral immunity by producing, developing and releasing large quantities of antibodies against cancer. Clinical evidence from a human model of breast cancer patients supports this hypothesis
  • There is also evidence that confirms the tumoricidal role of Gc-MAF via Fc-receptor mediation
  • It is likely that the best therapeutic responses will be observed when the nutritional and inflammatory aspects are taken together with stimulation of the immune system
  • it should be noted that no harmful side effects of Gc-MAF treatment have been reported, even when it was successfully administered to autistic children
  • The natural activation mechanism of macrophages by Gc-MAF is so natural and it should not have any side effects on humans or animal models even in cell culture
  • Besides the Gc-MAF efficacy on macrophage activity, it can be a potential anti-angiogenic agent (28) and an inhibitor of the migration of cancerous cells in the absence of macrophages (47).
  • Activating or modifying natural killer cells, dendritic cells, DC, CTL, INF and IL-2 have all been recommended for cancer immunotherapy
  • It has been reported that nagalase cannot deglycosylate Gc-MAF as it has specificity for Gc globulin alone
  • inflammation-derived macrophage activation with the participation of B and T lymphocytes is the main mechanism
  • macrophages highly-activated by the addition of Gc-MAF can show tumoricidal activity
  • Previous clinical investigations have confirmed the efficacy of Gc-MAF. In addition to activating existing macrophages, Gc-MAF is a potent mitogenic factor that can stimulate the myeloid progenitor cells to increase systemic macrophage cell counts by 40-fold in four days
  •  
    great review on Gc-MAF in cancer.  An increase in nagalase blocks Gc-protein to Gc-MAF activity leaving the host immune system compromised.
Nathan Goodyear

Immunotherapy targets metastatic breast cancer-cell mutations - National Cancer Institute - 0 views

  •  
    This is simply a press release from the NCI, but it highlights the move to immunotherapy as the future of cancer therapy.
Nathan Goodyear

Cancer immunotherapy comes of age - 0 views

  •  
    another nice review of immunotherapy in cancer; though the use of immunotherapy is becoming blurry based on who is using the term.
Nathan Goodyear

Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in ... - 0 views

  • Rigvir is a 2 ml frozen solution
  • ECHO-7 virus strain, Picornaviridae family, Enterovirus genus, Enteric Cytopathic Human Orphan (ECHO) type 7, group IV, positive-sense single-stranded RNA virus
  • a few side effects were reported, for example subfebrile temperature (37.5°C for a couple of days), pain in the tumour area, sleepiness and diarrhoea
  • ...12 more annotations...
  • In this retrospective study, however, there was no record of any untoward side effect from Rigvir treatment or its discontinuation
  • Early observations of tumour regressions after virus infections have been published starting from the late 19th century
  • The present results show that in substage IB, IIA, IIB and IIC melanoma patients, Rigvir administration after surgery significantly (P<0.05) prolongs survival compared with patients who were managed according to current published guidelines
  • no value higher than grade 2 was recorded in Rigvir-treated patients. This is in contrast to most other cancer therapies, where grades 3 and 4 are frequently observed
  • Administration of virus induces the formation of neutralising antibodies that might potentially influence the efficiency of Rigvir
  • In 94 healthy adult participants tested, the titres were found to be low (1 : 20 to 1 : 62) 39,40. When tested in 155 adult cancer patients who had not been treated with Rigvir, neutralising antibodies against ECHO-7 were detected in ∼50% of the patients
  • the presence of ECHO-7 antibodies was shown to increase with age in children and level off to a plateau of around 75% in adults
  • Rigvir is an immunomodulator that affects both the humoral, antibody-mediated, and the cellular immune systems
  • neutralising antibodies do not affect efficacy when local or regional administration is used
  • it reduces the viability of melanoma, as well as pulmonary, gastric, pancreatic, bone, and breast cancer cell cultures
  • It is oncolytic in melanoma and rectum cancer patients
  • shown to improve the 5-year survival in rectum cancer patients
  •  
    RIGVIR shown to improve survival against standard therapy in stage IB, IIA, IIB, and IIC in malignant melanoma patients in retrospective study. Side effects are minimal. Neutralizing antibodies are an area to watch that likely effects individual outcome beyond that of the type of cancer
Nathan Goodyear

Phase II Randomized Trial of Autologous Formalin-Fixed Tumor Vaccine for Postsurgical R... - 0 views

  •  
    Specific immunotherapy from patient the specific antigens of cancer cells fixed in formalin improves survival in hepatocellular cancer.
Nathan Goodyear

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor,... - 0 views

  • the MAF precursor activity of prostate cancer patient Gc protein is lost or reduced, because their serum Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells
  • Administration of 100 ng of GcMAF
  • 100 ng of GcMAF was administered intramuscularly once a week
  • ...11 more annotations...
  • As GcMAF therapy progressed the MAF precursor activity of all five patients increased and their serum Nagalase activity decreased inversely
  • As GcMAF therapy progressed, the MAF precursor activity increased with a concomitant decrease in serum Nagalase activity
  • serum Nagalase is proportional to tumor burden
  • as GcMAF therapy progressed, serum Nagalase activity decreased and, concomitantly, tumor burden decreased
  • the serum Nagalase activities of all 16 patients decreased as GcMAF therapy progressed
  • annual computed tomographic scans of these patients confirmed them being tumor recurrence-free for the 7 years
  • undifferentiated cells were killed rapidly during the first few weeks, and the differentiated cells were killed slowly in the remaining GcMAF therapeutic period
  • PSA levels of prostatectomized patients decreased as serum Nagalase decreased during GcMAF therapy
  • In patients without tumor resection, however, although serum Nagalase activity decreased as GcMAF therapy progressed, their PSA values remained unchanged. The result suggests that the PSA derived from tumor-bearing prostate did not change while tumor burden decreased. Because tumor-induced inflammation in the noncancerous prostate tissues causes secretion of PSA [38], the PSA produced from these inflamed noncancerous prostate tissues cannot be changed by the decrease in tumor burden
  • Advanced cancer patients have high serum Nagalase activities, resulting in no macrophage activation and severe immunosuppression that explain why cancer patients die with overwhelming infection
  • Prognostic utility of serum α-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients
  •  
    GC-MAF levels exist in inverse relationship to nagalase.  In this study of men with prostate cancer, weekly GCMAF injections reduced Nagalase activity to levels found in healthy controls suggesting tumor free. The dose was 100 ng/week. Nagalase is a protein that suppresses GC-MAF production and thus is immunosuppressive.
Nathan Goodyear

Oncolytic viruses as engineering platforms for combination immunotherapy | Nature Revie... - 0 views

  •  
    Only abstract available here, but good opinion piece on the future, here and now, in the field of immunotherapy in the treatment of cancer-oncolytic virus. Of course, they focus on the genetic altered virus', yet an unaltered enterovirus currently exists on the market.
Nathan Goodyear

PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Com... - 0 views

  •  
    Good review of PD-1 and PDL-1 siganling in the immune system in cancer immunotherapy.
Nathan Goodyear

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead - 0 views

  •  
    great review of the history of immunotherapy in cancer treatment
Nathan Goodyear

A CLINICAL-STUDY OF IMMUNOTHERAPY VERSUS ENDOCRINE THERAPY VERSUS CHEMOTHERAPY IN THE T... - 0 views

  •  
    Head to head study of IL-2 + melatonin versus chemotherapy in advanced pancreatic cancer found slightly better outcomes in the immunotherapy arm versus standard chemotherapy.  This difference was statistically significant.
Nathan Goodyear

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer t... - 0 views

  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
  • ...15 more annotations...
  • shortened survival and an increased risk of disease recurrence and metastasis
  • Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
  • biosimilars
  • trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
  • concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
    • Nathan Goodyear
       
      avoid herceptin in conjuction with antracyclines i.e. doxorubicin
  • Sequential doxorubicin plus cyclophosphamide followed by concomitant paclitaxel or docetaxel and trastuzumab is recommended for most patients
    • Nathan Goodyear
       
      top recommended regimen combination
  • Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
    • Nathan Goodyear
       
      good alternative in patients with increased risk of cardiac toxicity.
  • guidelines recommend up to 1 year of adjuvant trastuzumab
  • Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
  • the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
  • recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
  • neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
  • Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
  • dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
  • the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
  •  
    HER-2 + breast cancer = appx 15-20% of all breast cancers and is a marker of worse prognosis and an indication for targeted immunotherapy blockade.
Nathan Goodyear

Update on Programmed Death-1 and Programmed Death-Ligand 1 Inhibition in the Treatment ... - 0 views

  • Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the first immune checkpoint receptor to be clinically targeted, is exclusively expressed on the surface of CD4+ and CD8+ T cells in lymphatic tissue and is involved in T-cell regulation, proliferation, and tolerance
  • programmed death-1 (PD-1) immune checkpoint inhibitor antibodies, which restores T-cell effector function and augments the host anti-tumor response by blocking the binding of either programmed death-ligand 1 (PD-L1) and/or PD-L2 to PD-1 receptors
  • lung cancer is the first and second cause of cancer mortality in men and women
  • ...1 more annotation...
  • Eighty-five percent of lung cancers are non-small-cell lung cancer (NSCLC)
  •  
    To read update article on PD-1 and immunotherapy.
Nathan Goodyear

Hyperthermia as an immunotherapy strategy for cancer - 1 views

  • the notion of treating human cancers with heat dates back to the writings of Hippocrates
  • enhance the efficiency of standard cancer therapies, such as chemotherapy and radiation treatment
  • After antigen uptake at tumor sites, APCs have the ability to create a robust response by entering lymphoid compartments and programming lymphocytes
  • ...36 more annotations...
  • Hyperthermia differs fundamentally from fever in that it elevates the core body temperature without changing the physiological set point
  • hyperthermia is induced by increasing the heat load and/or inactivating heat dissipation
  • mor cells [2]. Although significant cell killing could be achieved by heating cells or tissues to temperatures > 42°C for 1 or more hours, the application, measurement and consistency of this temperature range within the setting of cancer clinical trials
  • mild temperature hyperthermia (ie, within the fever-range, 39–41°C)
    • Nathan Goodyear
       
      101.2 to 105.8
  • moderate hyperthermia (41°C)
    • Nathan Goodyear
       
      105.8 F
  • Hsps are a family of stress-induced proteins
  • they are key regulators of cellular protein activity, turnover and trafficking
  • Hsps ensure appropriate post-translational protein folding, and are able to refold denatured proteins, or mark irreversibly damaged proteins for destruction
  • the ability of fever-range hyperthermia to induce reactive immunity against tumor antigens through DCs and NK-cells is likely mediated by Hsps
  • thermotolerance
  • Hsps support the malignant phenotype of cancer cells by not only affecting the cells’ survival, but also participating in angiogenesis, invasion, metastasis and immortalization mechanisms
  • Hsps released from stressed or dying cells activate dendritic cells (DCs), transforming them into mature APCs
  • In theory, fever-range hyperthermia may take advantage of tumor cell Hsps by inducing their release from tumor cells and augmenting DC priming against tumor antigens
  • In several models of hyperthermia, heat-treated tumors exhibited improved DC priming and generation of systemic immunity to tumor cell
  • hyperthermia alone can enhance antigen display by tumor cells, thus rendering them even more susceptible to programmed immune clearance
  • Fever-range hyperthermia may also induce Hsps
  • Hsps may exert an adjuvant effect by bolstering MHC class II and co-stimulatory molecule expression by DCs
  • thermal ablation of liver tumors in particular has demonstrated an ability to potentiate immune responses [57, 58] and elicit robust T-cell infiltrates at ablation sites
  • specific Hsp, Hsp70, directly inhibits apoptosis pathways in cancer cells, as demonstrated in human pancreatic, prostate and gastric cancer cells
  • Cross-priming is the ability of extracellular Hsps complexed to tumor peptides to be internalized and presented in the context of MHC class I molecules on APCs, thus allowing potent priming of CTLs against tumor antigens
  • It has been reported that Hsps are generated from necrotic tumor cell lysates, but not from tumor cells undergoing apoptosis
  • tumor cells exposed to hyperthermia in the heat shock range (42°C for 4h) prior to lysing, DC activation and cross-priming were significantly enhanced with the application of heat
  • Due to the ability of Hsps to activate DCs directly by chaperoning tumor antigens upon their release [28], it is possible that both local and regional immune stimulation can be achieved with hyperthermia.
  • support the use of hyperthermia as an inducer of Hsps to serve as ‘danger signals’, activating antitumor immune responses
  • whole-body hyperthermia not only augments immune responses, but also stimulates the migration of skin-derived DCs to draining lymph nodes
    • Nathan Goodyear
       
      This allows for the activation of lymphocytes by the activated dendritic cells.
  • suggest a valuable role of hyperthermia in DC cancer vaccine strategies
  • In mice treated with fever-range whole-body hyperthermia, tumor growth was significantly inhibited and NK-cell infiltration increased
    • Nathan Goodyear
       
      Hyperthermia increased NK cell activation, proliferation, and infiltration, which equals increased cytotoxicity.
  • exposure to fever-range hyperthermia resulted in improved endogenous NK-cell cytotoxicity to several cancer types
  • improved activation and function of DCs and NK cells following hyperthermia
  • Hyperthermia increases the expression ICAM-1 a key adhesion molecule,
  • The combined effects of hyperthermia on lymphoid tissue endothelium and lymphocytes can promote immune surveillance and increase the probability of naive lymphocytes leaving the circulation and encountering their cognate antigen displayed by DCs in lymphoid organs.
  • In independent clinical studies, whole-body hyperthermia resulted in a transient decrease in circulating lymphocytes in patients with advanced cancer [12, 94, 99, 100], a finding which mirrored observations in animal models in which lymphocyte entry into lymph noeds was increased following hyperthermia treatment [93]. Enhanced recruitment of lymphocytes to lymphoid tissues may be exploited in the treatment of malignancies.
  • The initial tumor antigen presentation and initiation of clonal expansion of CTLs transpires in the lymph nodes and cannot take place outside this specialized compartment
  • the ability of DCs present in the lymph nodes to stimulate an anti-tumor immune response is critical
  • hyperthermia has been shown to improve immune surveillance by T-cell
  • and to increase DC trafficking to lymph nodes
  •  
    Great review of hyperthermia.
Nathan Goodyear

High-dose vitamin C enhances cancer immunotherapy - 0 views

  •  
    Absolute must read. IVC augments immune system and immunotherapy.
Nathan Goodyear

Impact of acetaminophen on the efficacy of immunotherapy in cancer patients - Annals of... - 0 views

  •  
    Tylenol blunts immunotherapy treatment efficacy.
Nathan Goodyear

Immunotherapy in People with Cancer and Autoimmune Diseases - NCI - 0 views

  •  
    Quote that 30% of cancer patients have coexisting autoimmune disease. No real reference for that percentage.
Nathan Goodyear

Adjuvant histamine in cancer immunotherapy, Seminars in Cancer Biology | 10.1006/scbi.2... - 0 views

  •  
    histamine dihydrochloride augments IL-2 stimulation of NK and blocks the monocyte/macrophage inhibition of IL-2 stimulation of NK cells.
Nathan Goodyear

Combining surgery and immunotherapy: turning an immunosuppressive effect into a therape... - 0 views

  •  
    The post-operative time period is critical to the long-term metastatic risk of cancer because surgery suppresses the immune system in this critical post-operative time period.
Nathan Goodyear

The role of opioids in cancer response to immunotherapy | Journal of Translational Medi... - 0 views

  •  
    opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well.
1 - 20 of 224 Next › Last »
Showing 20 items per page