Glycans as targets for therapeutic antitumor antibodies

2012 ◽  
Vol 8 (8) ◽  
pp. 943-960 ◽  
Author(s):  
Catherine Rabu ◽  
Richard McIntosh ◽  
Zuzana Jurasova ◽  
Lindy Durrant
Keyword(s):  
Antitumor Antibodies

scholarly journals Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies

2021 ◽  
Vol 9 (4) ◽  
pp. e002193
Author(s):  
Sigrid P Dubois ◽  
Milos D Miljkovic ◽  
Thomas A Fleisher ◽  
Stefania Pittaluga ◽  
Jennifer Hsu-Albert ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Intravenous Infusion ◽  
Nk Cell ◽  
Continuous Intravenous Infusion ◽  
Dose Escalation Study ◽  
Link Type ◽  
Best Response ◽  
Antitumor Antibodies ◽  
Interleukin 15

BackgroundFull application of cytokines as oncoimmunotherapeutics requires identification of optimal regimens. Our initial effort with intravenous bolus recombinant human interleukin-15 (rhIL-15) was limited by postinfusional reactions. Subcutaneous injection and continuous intravenous infusion for 10 days (CIV-10) provided rhIL-15 with less toxicity with CIV-10 giving the best increases in CD8+ lymphocytes and natural killer (NK) cells. To ease rhIL-15 administration, we shortened time of infusion. Treatment with rhIL-15 at a dose of 3–5 µg/kg as a 5-day continuous intravenous infusion (CIV-5) had no dose-limiting toxicities while effector cell stimulation was comparable to the CIV-10 regimen.MethodsEleven patients with metastatic cancers were treated with rhIL-15 CIV-5, 3 µg (n=4), 4 µg (n=3), and 5 µg/kg/day (n=4) in a phase I dose-escalation study (April 6, 2012).ResultsImpressive expansions of NK cells were seen at all dose levels (mean 34-fold), including CD56bright NK cells (mean 144-fold for 4 µg/kg), as well as an increase in CD8+ T cells (mean 3.38-fold). At 5 µg/kg/day, there were no dose-limiting toxicities but pulmonary capillary leak and slower patient recovery. This led to our choice of the 4 µg/kg as CIV-5 dose for further testing. Cytolytic capacity of CD56bright and CD56dim NK cells was increased by interleukin-15 assayed by antibody-dependent cellular cytotoxicity (ADCC), natural cytotoxicity and natural killer group 2D-mediated cytotoxicity. The best response was stable disease.ConclusionsIL-15 administered as CIV-5 substantially expanded NK cells with increased cytotoxic functions. Tumor-targeting monoclonal antibodies dependent on ADCC as their mechanism of action including alemtuzumab, obinutuzumab, avelumab, and mogamulizumab could benefit from those NK cell expansions and provide a promising therapeutic strategy.Trial registration numbersNCT01572493, NCT03759184, NCT03905135, NCT04185220 and NCT02689453.

Abstract 3966: Mining the cancer immuno-responsome: The identification of functional antitumor antibodies from patients receiving checkpoint inhibitors

2018 ◽  
Author(s):  
Gilson Baia ◽  
Amy Manning-Bog ◽  
Alexander Scholz ◽  
Jeff DeFalco ◽  
Michael Harbell ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Antitumor Antibodies

Correlation between the Presence of Natural Antitumor Antibodies and Activation of Mulv Endogenous Virus in Balb/C Mice

1981 ◽  
Vol 67 (4) ◽  
pp. 283-292 ◽  
Author(s):  
Sylvie Ménard ◽  
Maria I. Colnaghi ◽  
Elda Tagliabile
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Serum Level ◽  
Tumor Cells ◽  
Cytotoxic Effect ◽  
Spleen Cells ◽  
Endogenous Virus ◽  
Cell Compartment ◽  
Cytotoxic Antibodies ◽  
Antitumor Antibodies

Individual 3-month-old or 12-month-old BALB/c mice, as well as 5-month-old nu/nu or nu/ + BALB/c mice, showed a direct correlation between the serum level of natural antitumor cytotoxic antibodies and the capacity of spleen cells to infect SC-1 cells permissive for murine ecotropic viruses. Pooled or individual sera from 3-month-old BALB/c mice, negative for the presence of natural antitumor cytotoxic antibodies and whose spleen cells were unable to infect the SC-1 cells, were negative both for SC-1 cells and SC-1 cells infected by MuLV. On the contrary, pooled or individual sera from 15-month-old BALB/c mice, positive for the presence of natural antitumor antibodies and with infecting spleen cells, were cytotoxic for infected SC-1 cells but not for the uninfected ones. The infection of SC-1 cells by MuLV could be inhibited by 3-month-old spleen cells, and this effect was suppressed by depriving the inhibiting spleen cells of T cells by means of an anti-Thy-1 antibody plus complement. The cells with infectious capacity did not belong to the T-cell compartment, as demonstrated by the lack of infection after passing the infecting spleen cells through an anti-Ig column, whereas T-deprivation did not modify the infectious capacity. A natural anti-gp70 monoclonal antibody, which exerted a complement-dependent cytotoxic effect on tumor cells, stronghly inhibited the infection of the permissive SC-1 cells by MuLV.

Production of recombinant antitumor antibodies by HEK-293 cells

2006 ◽  
Vol 406 (1) ◽  
pp. 44-46 ◽  
Author(s):  
S. M. Deyev ◽  
O. A. Stremovskiy ◽  
S. V. Lukash ◽  
D. V. Karpenko ◽  
O. L. Polyanovsky ◽  
...  
Keyword(s):  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Antitumor Antibodies
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