In vitro tumor cell killing by peritoneal macrophages from mitomycin C-treated rats

1982 ◽  
Vol 13 (2) ◽  
Author(s):  
Takeshi Ogura ◽  
Hiroo Shindo ◽  
Osamu Shinzato ◽  
Manabu Namba ◽  
Tomiya Masuno ◽  
...  
Author(s):  
S CHMURA ◽  
M GAROFALO ◽  
J SALAMA ◽  
W SILVERBERG ◽  
J OH ◽  
...  

1993 ◽  
Vol 28 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Colin A. Bill ◽  
Elizabeth A. Mendoza ◽  
Eduard Vrdoljak ◽  
Philip J. Tofilon

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi84-vi85
Author(s):  
Jorge Jimenez Macias ◽  
Yen-Chun Lee ◽  
Tomer Finkelberg ◽  
Mykola Zdioruk ◽  
Gilles Berger ◽  
...  

Abstract INTRODUCTION Glioblastoma (GBM), an aggressive brain tumor with a poor prognosis, presents an average of 2% of patients surviving beyond 2 years after diagnosis. Therapies to effectively manage glioblastoma are hindered due to the presence of the blood-brain barrier (BBB). Previously, a cell-penetrating peptide, M13, was conjugated to a Pt(IV) cisplatin prodrug, via amide bond formation. The conjugated Pt(IV) releases active cisplatin upon intracellular reduction. Herein, we investigated the BBB-penetrance and biodistribution of M13 conjugated to Pt(IV), as well as its effectiveness against GBM in mouse models. METHODS M13 platinum-conjugate tumor cell killing capacity was assessed by luminescent cell viability assays in vitro. By using Inductively-Coupled Plasma Mass-Spectrometry for platinum detection, BBB penetration and bio-distribution studies were performed in a three-dimensional BBB spheroid in vitro model and in vivo in mouse brain, intracranial tumor, and peripheral organs. Dose-regime studies involved observations of symptomatology and weight variations after bi-weekly injections of platinum compounds at 2mg/kg and 5mg/kg. RESULTS The Pt(IV)-M13 conjugate possesses tumor cell killing effects similar to cisplatin when tested in GBM cell lines in vitro. Platinum increased by using Pt(IV)-M13 when compared to cisplatin in our in vitro BBB-spheroid model (20-fold, p-value=0.0033), in brain tissue (10-fold, p< 0.0001) and GBM tumor-bearing mice models (7.5-fold, p< 0.0001). Bio-distribution of platinum delivered by Pt(IV)-M13 in spleen, heart and blood was significantly different to cisplatin 5hrs. after intravenous injection (p< 0.001). Bi-weekly dose regimes of Pt(IV)-M13 are tolerable in nude mice without toxicity at a similar concentration to reported tolerable cisplatin doses at 5 mg/kg. Finally, Pt(IV)-M13 significantly increased survival in a murine glioblastoma xenograft model compared with controls (median 24 days vs. 29 days, p-value=0.0071). CONCLUSION Overall, our data support the further development of BBB-crossing peptide-drug conjugates for GBM treatment.


Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2526-2534 ◽  
Author(s):  
Peter Ruf ◽  
Horst Lindhofer

Abstract Bispecific antibodies (bsAbs) can efficiently mediate tumor cell killing by redirecting preactivated or costimulated T cells to disseminated tumor cells, especially in a minimal residual disease situation. This study demonstrates that the trifunctional bsAb BiLu is able to kill tumor cells very efficiently without any additional costimulation of effector cells in vitro and in vivo. Remarkably, this bsAb also induces a long-lasting protective immunity against the targeted syngeneic mouse tumors (B16 melanoma and A20 B-cell lymphoma, respectively). A strong correlation was observed between the induction of a humoral immune response with tumor-reactive antibodies and the survival of mice. This humoral response was at least in part tumor specific as shown in the A20 model by the detection of induced anti-idiotype antibodies. Both the survival of mice and antitumor titers were significantly diminished when F(ab′)2 fragments of the same bsAb were applied, demonstrating the importance of the Fc region in this process. With the use of T-cell depletion, a contribution of a cellular antitumor response could be demonstrated. These results reveal the necessity of the Fc region of the bsAb with its potent immunoglobulin subclass combination mouse immunoglobulin G2a (IgG2a) and rat IgG2b. The antigen-presenting system seems to be crucial for achieving an efficient tumor cell killing and induction of long-lasting antitumor immunity. Hereby, the recruitment and activation of accessory cells by the intact bsAb is essential.


1978 ◽  
Vol 38 (2) ◽  
pp. 276-285 ◽  
Author(s):  
Somesh D. Sharma ◽  
Willy F. Piessens

2004 ◽  
Vol 60 (1) ◽  
pp. S319-S320 ◽  
Author(s):  
S.J. Chmura ◽  
M. Garofalo ◽  
J. Salama ◽  
W. Silverberg ◽  
J. Oh ◽  
...  

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