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Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...PMC5686300

nagalase Gc-MAF cancer

shared by Nathan Goodyear on 29 Jan 18 - No Cached
  • 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
  • Nathan Goodyear on 29 Jan 18
     
    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

Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations - 0 views

www.ncbi.nlm.nih.gov/...PMC5950938

VAE mistletoe cancer monoclonal antibodies mAB IL-12 NK cells

shared by Nathan Goodyear on 06 Jun 18 - No Cached
  • Among the most encouraging mAb is trastuzumab, which targets the human epidermal growth factor receptor 2 and is indicated in the treatment of breast cancer
  • bevacizumab, which inhibits vascular endothelial growth factor and is indicated in the treatment of a range of diseases, including colorectal, lung, and ovarian cancer3; and cetuximab, which blocks the epidermal growth factor receptor and is indicated in the treatment of colorectal and lung cancer
  • Viscum album L (VA or European mistletoe) preparations are widely used as additive cancer therapy in Europe, especially in German-speaking countries, and have been associated with a reduction in chemotherapy-related adverse drug reactions and increased HRQL
  • ...6 more annotations...
  • leading to enhancement of interleukin-12 secretion and natural killer cell function
  • Helixor VA preparations
  • A multivariable GEE model indicated that the odds for patients experiencing an AE following mAb therapy were nearly 5 times higher compared with that for mAb plus VA
  • VA preparations (Iscador Ltd) did not inhibit chemotherapy-induced cytostasis or cytotoxicity and showed an additive inhibitory effect at higher concentrations of VA.
  • previous in vitro investigations have shown that VA preparations have either no or minor effects on a range of CYPs, suggesting that VA-drug interactions based on drug metabolism are unlikely
  • mAb do not undergo hepatic metabolism but undergo proteolytic catabolism throughout the body
  • Nathan Goodyear on 06 Jun 18
     
    VAE therapy found to reduce adverse events in those receiving monoclonal Ab therapy.
Nathan Goodyear

IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SA... - 0 views

www.ncbi.nlm.nih.gov/...PMC10222767

spike protein spike proteins IgG4 COVID19 COVID-19 COVID vaccination SARS-CoV-2

shared by Nathan Goodyear on 01 Jun 23 - No Cached
  • These mRNA vaccines represented a new type of vaccine that comprises synthetic mRNA molecules that contain the coding sequence necessary to build the SARS-CoV-2 Spike protein, which is encased in the lipid nanoparticles (LNPs) to allow for the delivery of mRNA to cells.
  • proteins are synthesized within the host cells
  • they can induce significant neutralizing anti-spike IgG and IgA response
  • ...3 more annotations...
  • Lethal COVID-19 cases have been linked to higher levels of IgG4 antibodies
  • mRNA vaccines trigger their synthesis
  • provide the scientific rationale suggesting that repeated vaccination with mRNA vaccines could generate an immune tolerance mechanism, thereby favoring unopposed SARS-CoV-2 replication.
Nathan Goodyear

Journal of Endocrinological Investigation - 0 views

www.jendocrinolinvest.it/...abstract.cfm

thyroid cancer thyroid nodules nodules TSH autoimmune TPO anti-thyroglobulin antibodies

shared by Nathan Goodyear on 28 May 13 - No Cached
  • Nathan Goodyear on 28 May 13
     
    elevated autoimmune markers against the thyroid and an elevated TSH are both independent risk factors for thyroid malignancy in those with thyroid nodules.
Nathan Goodyear

Do salivary antibodies reliably reflect bot... [Ann N Y Acad Sci. 2007] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17435136

saliva salivary SIgA GALT inflammation

shared by Nathan Goodyear on 30 May 12 - No Cached
  • Nathan Goodyear on 30 May 12
     
    saliva SIgA show to be associated with B cell activity in the GALT.
Nathan Goodyear

Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): N... - 0 views

press.endocrine.org/...jcem.87.2.8182

hypothyroid hypothyroidism thyroid TSH hormones

shared by Nathan Goodyear on 24 Sep 14 - No Cached
  • Nathan Goodyear on 24 Sep 14
     
    This article finds the mean TSH level in the "healthy" population to be 1.5.  Calls into question any level above that with symptoms of hypothyroid.  Full, adequate thyroid including free T3 and rT3 must be done.
Nathan Goodyear

Reduced seroconversion to measles in infants given... [Lancet. 1995] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...7752754

vitamin A measles virus

shared by Nathan Goodyear on 20 May 11 - No Cached
  • vitamin A may limit replication of vaccine-strain measles vaccine
  • These results suggest that simultaneous high- dose vitamin A may thwart seroconversion to live measles vaccine in infants with maternal antibodies.
  • Nathan Goodyear on 20 May 11
     
    Vitamin A limits replication of measles virus
Nathan Goodyear

Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic... - 0 views

onlinelibrary.wiley.com/...abstract

probiotics gut inflammation insulin glucose

shared by Nathan Goodyear on 06 Apr 11 - No Cached
  • these results support the concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD and suggest novel therapies for these common conditions.
  • Nathan Goodyear on 06 Apr 11
     
    Gut inflammation plays role in insulin/glucose dysregulation and inflammation
Nathan Goodyear

Candida albicans Is an Immunogen for Anti-Saccharomyces cerevisiae Antibody Markers of ... - 0 views

www.gastrojournal.org/...abstract

candida albicans yeast crohn's disease

shared by Nathan Goodyear on 29 Jun 11 - No Cached
  • Nathan Goodyear on 29 Jun 11
     
    Yeast species appears to play role in abnormal immune response in Crohn's disease
Nathan Goodyear

Understanding and determining the etiology of auti... [Cell Mol Neurobiol. 2010] - PubM... - 0 views

www.ncbi.nlm.nih.gov/...19774457

autism ASD detoxification

shared by Nathan Goodyear on 05 Jul 11 - No Cached
  • Worldwide, the rate of autism has been steadily rising.
  • Genetic polymorphisms of cytochrome P450 enzymes have also been linked to autism, specifically CYP27B1 that is essential for proper vitamin D metabolism
  • There are several environmental factors in concert with genetic susceptibilities that are contributing to this rise. Impaired methylation and mutations of mecp2 have been associated with autistic spectrum disorders, and related Rett syndrome.
  • ...1 more annotation...
  • Other factors that have been considered include: maternally derived antibodies, maternal infection, heavy metal exposure, folic acid supplementation, epigenetics, measles, mumps, rubella vaccination, and even electromagnetic radiation.
  • Nathan Goodyear on 05 Jul 11
     
    Autism has many potential causes.  At the heart is poor detoxification
Nathan Goodyear

Hypercalcemia of malignancy and new treatment options - 0 views

www.ncbi.nlm.nih.gov/...PMC4675637

hypercalcemia calcium cancer

shared by Nathan Goodyear on 11 Sep 18 - No Cached
  • Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
  • ectopic secretion of parathyroid hormone (PTH) has been implicated
  • Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
  • ...22 more annotations...
  • Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
  • 20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
  • Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
  • In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
  • In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
  • Macrophage inflammation protein 1-alpha (MIP 1-alpha)
  • hypercalcemia is through extra-renal 1,25-dihydroxyvitamin D (calcitriol) production
  • 1% of cases
  • increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
  • 1-α-hydroxylase in the kidney, a process regulated by PTH
  • in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
  • this mechanism of disease is best conceptualized as an absorptive form of hypercalcemia
  • Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
  • primary hyperparathyroidism and malignancy comprising nearly 90% of cases of hypercalcemia
  • an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
  • Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
  • Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
  • mildly symptomatic disease
  • marked symptoms
  • hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
  • denosumab
  • Denosumab is an RANKL antibody that inhibits osteoclast maturation, activation, and function
  • Nathan Goodyear on 11 Sep 18
     
    hypercalcemia in cancer and treatments.
Nathan Goodyear

Multicenter Phase II Study of Sequential Brentuximab Vedotin and Doxorubicin, Vinblasti... - 0 views

ascopubs.org/...JCO.2018.79.0139

Hodgkin's lymphoma Hodgkin's disease lymphoma immunotherapy cancer chemotherapy monoclonal antibodies

shared by Nathan Goodyear on 13 Sep 18 - No Cached
  • Nathan Goodyear on 13 Sep 18
     
    monoclonal Ab used in sequence with AVD found to have event-free survival, progression-free survival, and overal survival rates of 80%, 84%, and 93% respectively in older adults with Hodgkin's lymphoma.
Nathan Goodyear

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multi... - 0 views

www.ncbi.nlm.nih.gov/...PMC5809128

cancer anal cancer nivolumab immunotherapy

shared by Nathan Goodyear on 13 Jul 18 - No Cached
  • Patients received a median of six doses of nivolumab
  • four of the first 12 patients had partial responses
  • Nine (24% [95% CI 15–33]) of 37 patients achieved a response (seven partial responses and two complete responses
  • ...16 more annotations...
  • no treatment-related deaths
  • the most common adverse events were anaemia (26 [70%]), fatigue (25 [68%]), and rash
  • hypothyroidism
  • hypothyroidism
  • nivolumab-related autoimmune hypothyroidism, which resolved after a short course of corticosteroids
  • No grade 3 or 4 adverse events occurred
  • Nivolumab resulted in objective responses in 24% of patients with metastatic SCCA
  • Historically, doublet chemotherapy with cisplatin and fluorouracil has been the most common treatment for patients with metastatic SCCA
  • our results suggest that immune checkpoint blockade agents might extend overall survival beyond currently available therapies, especially if provided early in the disease treatment course
  • the dose of nivolumab we used differs from the 2016 recommendation of a fixed 240 mg every 2 weeks
  • 25% of patients develop distant metastases
  • most patients with localised SCCA are cured by chemoradiation
  • More than 90% of cases of SCCA are linked to prior infection with human papillomavirus (HPV)
  • Within tumour cells, HPV oncoproteins are immunogenic and can trigger an anti-tumour host immune response by recruitment of tumour-infiltrating lymphocytes
  • Tumour cells express PD-L1 and, on binding its inhibitory receptor PD-1 on the surface of T cells, downregulate T-cell activation and thwart the local anti-tumour immune response
  • Nivolumab is a humanised monoclonal antibody against PD-1 that disrupts this interaction, enabling T-cell cytotoxicity. It has activity as a monotherapy in advanced solid cancers, such as head and neck cancer, melanoma, non-small-cell lung cancer, and renal cell carcinoma
  • Nathan Goodyear on 13 Jul 18
     
    study finds nivolumab helpful in some patients with surgically unresectable or metastatic anal cancer.  The dose used was 3 mg/kg every 2 weeks. 
Nathan Goodyear

Approved Drugs > Modification of the Dosage Regimen for Nivolumab - 0 views

www.fda.gov/...ucm520871.htm

immunotherapy cancer nivolumab monoclonal antibodies

shared by Nathan Goodyear on 13 Jul 18 - No Cached
  • Nathan Goodyear on 13 Jul 18
     
    FDA recommends nivolumab, PD-1 inhibitor immunotherapy, at 240 mg IV Q2 weeks.
Nathan Goodyear

Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on g... - 0 views

www.ncbi.nlm.nih.gov/...PMC4741919

adenoid cystic carcinoma

shared by Nathan Goodyear on 03 Oct 18 - No Cached
  • Cisplatin and 5-FU or CAP (cisplatin, doxorubicin, and cyclophosphamide) regimens can be used for combination chemotherapy
  • patients with advanced salivary gland malignancy treated with the CAP regimen achieved partial response (PR) or stable disease (SD) rates of 67% (8 out of 12 patients)
  • Agents commonly given as monotherapy for treating ACC are cisplatin, mitoxantrone, epirubicin, vinorelbine, paclitaxel, and gemcitabine. However, few of these agents have shown efficacy
  • ...23 more annotations...
  • single agent mitoxantrone or vinorelbine were recommended as reasonable choices
  • ACC is subdivided into 3 histological groups based on solid components of the tumor including cribriform, tubular, and solid
  • Cribriform and tubular ACCs usually exhibit a more indolent course, whereas the solid subtype is associated with worse prognosis
  • ACC consists of two different cell types: inner luminal epithelial cells and outer myoepithelial cells
  • epithelial cells express c-kit, cox-2 and Bcl-2
  • myoepithelial cells express EGFR and MYB
  • a balanced translocation of the v-myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B (MYB-NFIB) is considered to be a signature molecular event of ACC oncogenesis
  • As a transcription factor, MYB is known to modulate multiple genetic downstream targets involved in oncogenesis, such as cox-2, c-kit, Bcl-2 and BclX
  • Various signaling cascades are essential for cancer cells to survive and grow. The PI3K/Akt/mTOR pathway is one of them
  • This pathway regulates cell survival and growth and is upregulated in many cancers
  • Mutations in genes associated with DNA repair are frequently found in familial cancer syndromes, such as hereditary breast-ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC, also called Lynch syndrome) and Li-Fraumeni syndrome [30, 31]. These mutations were also reported in non-hereditary cancers
  • 70% of ACC samples (58 of 84) were found to have genetic alterations in the MYB/MYC pathway, indicating that changes in this pathway are crucial in ACC pathogenesis
  • The second most frequently mutated pathway was involved in chromatin remodeling (epigenetic modification), a pathway that includes multiple histone related proteins, and was altered in 44% of samples
  • C-kit
  • VEGF, iNOS and NF-κB were noted to be highly expressed in ACC cells as compared to normal salivary gland cells
  • members of the SOX family, such as SOX 4 and SOX10, are overexpressed in ACC
  • FABP7 (Fatty acid binding protein 7) and AQP1 (Aquaporin 1) tend to be overexpressed in ACC cell lines
  • considerable variability in HER2 overexpression ranging from 0–58% in patients with ACC
  • the study with cetuximab and concurrent chemoradiation or chemotherapy showed the highest ORR (total 43%, 9.5% CR and 33% PR), but this regimen was only given to the EGFR positive patients
  • Cancer immunotherapy can be classified into 3 major groups. Active immunization using anti-tumor vaccines to induce and recruit T cells, passive immunization based on monoclonal antibodies, and adoptive cell transfer to expand tumor-reactive autologous T cells ex vivo and then reintroduce these cells into the same individual
  • LAK cells showed cytotoxicity against ACC cells
  • cytokine-induced cell apoptosis and the cytotoxic effect of the LAK cells contributed to tumor regression
  • molecular finding of the MYB-NFIB fusion gene has the greatest potential to target what appears to be a fundamental event in disease pathogenesis
  • Nathan Goodyear on 03 Oct 18
     
    good review of adenoid cystic carcinoma
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...PMC5382272

cancer PD-1 immunotherapy programmed death-1

shared by Nathan Goodyear on 20 Apr 18 - No Cached
  • 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)
  • Nathan Goodyear on 20 Apr 18
     
    To read update article on PD-1 and immunotherapy.
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views

onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J

IL-2 breast cancer cancer NK cells HER-2 immunotherapy

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
  • ...17 more annotations...
  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
  • Nathan Goodyear on 18 Jun 18
     
    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection ... - 0 views

www.ncbi.nlm.nih.gov/...PMC8095229

COVID COVID19 COVID-19

shared by Nathan Goodyear on 27 Jul 21 - No Cached
  • Nathan Goodyear on 27 Jul 21
     
    Only natural immunity through infection provides the most durable B and T cells for long-term immunity. Vaccinations miss the mark.
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