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Actemra

Manufactured by Genentech
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Sourced in Cameroon

Actemra is an injectable medication used in the treatment of certain autoimmune and inflammatory conditions. It is a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, a key mediator of inflammatory processes in the body. Actemra is designed to block the signaling of IL-6, thereby reducing inflammation and immune system activity.

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Lab products found in correlation

Etanercept, by Amgen (1 mentions) Rneasy kit, by Qiagen (1 mentions) Gapdh, by Thermo Fisher Scientific (1 mentions) Sybr green chemistry, by Thermo Fisher Scientific (1 mentions) Taqman chemistry, by Thermo Fisher Scientific (1 mentions) Socs3, by Thermo Fisher Scientific (1 mentions) U937 cells, by American Type Culture Collection (1 mentions) Tocilizumab, by Genentech (1 mentions) Doxycyline, by Merck Group (1 mentions) Bms 345541, by Merck Group (1 mentions) Ruxolitinib, by Selleck Chemicals (1 mentions) Sb203580, by Cell Signaling Technology (1 mentions)

Spelling variants of this product

Tocilizumab/Actemra (3 citations)

7 protocols using actemra

1

Baboon Xenograft Induction Therapy

Cited 2 times
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All baboons received thymoglobulin (ATG) and anti-CD20mAb (Rituximab) as induction therapy. Maintenance immunosuppressive regimens are summarized in Table 1 (together with other information, e.g., graft survival and cause of death). The immunosuppressive regimens were either anti-CD40mAb-based or conventional therapy-based (which consisted of only FDA-approved agents – with various combinations of CTLA4-Ig, tacrolimus, rapamycin, mycophenolate mofetil) (21 (link)–23 (link)). Anti-CD40mAb (2C10R4, a chimeric rhesus IgG4) was provided by the NIH NHP Reagent Resource (24 (link)). Anti-inflammatory therapy was administered in an attempt to reduce inflammation. All baboons received interleukin-6 receptor (IL-6R) blockade with tocilizumab (10mg/kg on days −1, 7, 14, and thereafter every 2 weeks; Actemra, Genentech, South San Francisco, CA), and the TNF-αantagonist, etanercept (0.5mg/kg on days 0, 3, 7, and 10, Amgen, Thousand Oaks, CA).
Zhang G., Iwase H., Li Q., Yamamoto T., Jagdale A., Ezzelarab M.B., Ayares D., Cooper D.K., Hara H, & Wang G. (2021). The Role of Interleukin-6 (IL-6) in the Systemic Inflammatory Response in Xenograft Recipients and in Pig Kidney Xenograft Failure. Frontiers in Immunology, 12, 788949.
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2

Tocilizumab Modulates IL-6 Response in Monocytes

Cited 1 time
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Human monocytes from healthy donors were pre-incubated with or without 0.5 mg/mL tocilizumab and then incubated with or without recombinant human IL-6 (0.1ug/ml), normal donor plasma, or patient plasma for an additional 30 minutes in IMDM supplemented with 1.0% human A/B serum. Tocilizumab (Actemra™, Genentech) was purchased through the Hospital of the University of Pennsylvania Pharmacy. Following stimulation, culture medium was removed, cells were lysed directly in TRIzol, and RNA was isolated using a Qiagen RNeasy Kit per manufacturer instructions. cDNA was synthesized from 0.5 – 1.0 μg of RNA per sample (Applied Biosystems, Foster City, CA), and primers for qRT-PCR were designed using the Primer 3 online program (25 (link), 26 (link)) and synthesized by Integrated DNA Technologies (SOCS3) or purchased from Applied Biosystems (GAPDH). Relative quantification was measured using either SYBR Green chemistry (Applied Biosystems; SOCS3) or Taqman chemistry (Applied Biosystems; GAPDH). SOCS3 expression was normalized to GAPDH and relative expression was calculated using the ΔCT formula. The fold increase or decrease in expression of treated samples relative to no treatment controls was calculated (ΔΔCT). Primer sequences for human SOCS3 are as follows: (i) Forward: 5′-CAAGGACGGAGACTTCGATT-3′, (ii) Reverse: 5′-AACTTGCTGTGGGTGACCAT-3′.
Long K.B., Tooker G., Tooker E., Luque S.L., Lee J.W., Pan X, & Beatty G.L. (2017). IL-6 receptor blockade enhances chemotherapy efficacy in pancreatic ductal adenocarcinoma. Molecular cancer therapeutics, 16(9), 1898-1908.
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3

Xenotransplantation Immunosuppression Protocols

Cited 1 time
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For the xenoTx experiments, immunosuppressive therapy was based on costimulation blockade using either (i) anti-CD154mAb (Group 1A) or (ii) anti-CD40mAb (Group 1B) or (iii) CTLA4-Ig +/− anti-CD40mAb (2C10R4) (Group 2A and B) (12 ,16 ) (Table 1). In addition, two baboons with artery patch grafts (Group 2B) received IL-6R blockade with tocilizumab (Actemra, Genentech, South San Francisco, CA) (21 (link)) which, to our knowledge, has not been tested in a large animal model of xenotransplantation previously. For the alloTx experiments, immunosuppressive therapy was based on alemtuzumab (19 (link)).
Iwase H., Ekser B., Zhou H., Liu H., Satyananda V., Humar R., Humar P., Hara H., Long C., Bhama J.K., Bajona P., Wang Y., Wijkstrom M., Ayares D., Ezzelarab M.B, & Cooper D.K. (2015). FURTHER EVIDENCE FOR SUSTAINED SYSTEMIC INFLAMMATION IN XENOGRAFT RECIPIENTS (SIXR). Xenotransplantation, 22(5), 399-405.
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4

Xenotransplantation Immunosuppression Protocols

Cited 2 times
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For the heart or artery patch xenoTx experiments, immunosuppressive therapy was based on costimulation blockade using either (i) anti-CD154mAb or (ii) CTLA4-Ig +/− anti-CD40mAb (2C10R4) or (iii) anti-CD40mAb (17 (link)-19 (link),21 (link)) (Table1). Two immunosuppressed baboons with pig artery patch grafts also received IL-6R blockade (tocilizumab, [10mg/kg] Actemra, Genentech, South San Francisco, CA). In the liver xenoTx (21 (link)), immunosuppressive therapy was based on induction with ATG or cyclophosphamide (+ tacrolimus/ mycophenolate mofetil/ corticosteroids). In heart alloTx (23 (link)) experiments, immunosuppressive therapy was based on ATG (+ tacrolimus / rapamycin) or alemtuzumab (+ mycophenolate mofetil / rapamycin).
Iwase H., Ekser B., Hara H., Ezzelarab M.B., Long C., Thomson A.W., Ayares D, & Cooper D.K. (2016). THYROID HORMONE: RELEVANCE TO XENOTRANSPLANTATION. Xenotransplantation, 23(4), 293-299.
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5

Suppressing IL-6Rα Immunoreactivity with TCZ

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The capacity of JNP-released TCZ to suppress IL-6Rα immunoreactivity was evaluated using an hL-6Rα alpha DuoSet ELISA (R&D Systems, Minneapolis, MN). Concurrent assessments with stock TCZ (ACTEMRA, Genentech, San Francisco, CA) were conducted. Conditioned medium from a pleural effusion transformed histiocytic cell line (U937 cells, ATCC CRL 1593.2), which generated high levels of sIL-6Rα (pg/cell number), was used as an additional positive control to assess TCZ’s capacity to suppress IL-6Rα immunoreactivity. The in vitro studies (pretreat U937 cells) employed: 1.0 µg/mL of TCZ (ACTEMRA), 10 µg/mL of TCZ (ACTEMRA), or 1.0 µg/mL of JNP-released TCZ. Of note, 7.85 µg/mL of TCZ was the maximum reproducible level released from JNP among different lots. Control wells (no treatment) were included and all wells were incubated at 37ºC for 24 h. Impact was assessed by measuring percent reduction of sIL-6R and IL-6R levels compared to control (no treatment) and was adjusted to account for differences in cell densities measured at 24 h.
Habibi N., Bissonnette C., Pei P., Wang D., Chang A., Raymond J.E., Lahann J, & Mallery S.R. (2023). Mucopenetrating Janus Nanoparticles For Field-Coverage Oral Cancer Chemoprevention. Pharmaceutical Research, 40(3), 749-764.
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6

Immunosuppressive Xenotransplantation Protocols

Cited 3 times
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For the heart, kidney or artery patch xenotransplantation experiments, immunosuppressive therapy was based on costimulation blockade using either (i) anti-CD154mAb (NIH NHP Reagent Resource, Boston, MA) or (ii) CTLA4-Ig (BMS, Princeton, NJ) +/- anti-CD40mAb (2C10R4; NIH NHP Reagent Resource) or (iii) anti-CD40mAb30 (link)–32 (link),34 (link),35 (link) (Table 1). Nine immunosuppressed baboons with pig heart (n=2), kidney (n=5), or artery patch (n=2) grafts received interleukin-6 receptor (IL-6R) blockade with tocilizumab (10mg/kg; Actemra, Genentech, South San Francisco, CA). After liver xenotransplantation,32 (link) immunosuppressive therapy was based on tacrolimus/mycophenolate mofetil (MMF) (Table 1).
Li T., Lee W., Hara H., Long C., Ezzelarab M., Ayares D., Huang H., Wang Y., Cooper D.K, & Iwase H. (2017). AN INVESTIGATION OF EXTRACELLULAR HISTONES IN PIG-TO-BABOON ORGAN XENOTRANSPLANTATION. Transplantation, 101(10), 2330-2339.
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7

Antibody and Recombinant Protein Usage

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The antibodies used for western blotting, flow cytometry and immunohistochemistry are listed in the Key Resources Table. rPAI-1, rPAI-1 T333R A335R, rPAI-1 R76E I91L and RAP proteins were purchased from Molecular Innovations and used in experiments at a final concentration of 40 nM and 100 nM. Recombinant proteins tested negative by Endolisa assay (Hyglos) for the presence of endotoxin (LPS) (< 0.05 EU/μg of protein) (Table S1). Doxycyline (Sigma Aldrich) was dissolved in water at 10 mg/mL, filter sterilized (0.2 μm) and kept at −20°C in darkness. Actemra (Tocilizumab) was purchased from Genentech. SB203580 was purchased from Cell Signaling. BMS-345541 was purchased from Sigma-Aldrich. Ruxolitinib was purchased from Selleckchem. Inhibitors were dissolved in DMSO at a final 10 mM stock concentration.
Kubala M.H., Punj V., Placencio-Hickok V.R., Fang H., Fernandez G.E., Sposto R, & DeClerck Y.A. (2018). Plasminogen activator inhibitor-1 promotes the recruitment and polarization of macrophages in cancer. Cell reports, 25(8), 2177-2191.e7.
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