scholarly journals Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth.

1991 ◽  
Vol 88 (19) ◽  
pp. 8691-8695 ◽  
Author(s):  
I. Stancovski ◽  
E. Hurwitz ◽  
O. Leitner ◽  
A. Ullrich ◽  
Y. Yarden ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Growth ◽  
Erbb2 Receptor ◽  
Opposing Effects

scholarly journals Rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal antibodies against DKK2 for cancer therapy

2020 ◽  
Vol 3 (2) ◽  
pp. 63-70 ◽  
Author(s):  
Rongqing Zhao ◽  
Qian Xiao ◽  
Maohua Li ◽  
Wenlin Ren ◽  
Chenxi Xia ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Growth ◽  
Wnt Signaling ◽  
Rational Design ◽  
Polyclonal Antibodies ◽  
Wnt Signaling Pathway ◽  
Keyhole Limpet Hemocyanin ◽  
Linear Epitopes

Abstract Dickkopf-related protein 2 (DKK2)is a member of the Dickkopf family in Wnt signaling pathway. Recently, we found that antibodies against DKK2 could activate natural killer (NK) and CD8+ T cells in tumors and inhibit tumor growth. In this paper, we report the rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal anti-DKK2 antibodies. To break the immune tolerance, we designed and chemically synthesized six peptides corresponding to different regions of DKK2 as immunogens and found five of them could generate mouse polyclonal antibodies that can bind to the active recombinant human DKK2 protein. Neutralizing mouse monoclonal antibodies (5F8 and 1A10) against human DKK2 were successfully developed by immunizing the mice with two different peptides (34KLNSIKSSL42 and 240KVWKDATYS248) conjugated to Keyhole limpet hemocyanin (KLH). The monoclonal antibodies not only abolish DKK2’s suppression of Wnt signaling in vitro but also inhibits tumor growth in vivo. Currently, those two mAbs are undergoing humanization as immunotherapy candidates and may offer a new drug for treatment of human cancers.

scholarly journals A novel radio-sensitization method for lung cancer therapy: enhanced radiosensitization induced by antigens/antibodies reaction after targeting tumor hypoxia using Bifidobacterium

2020 ◽  
Author(s):  
Juan Yang ◽  
Zhouxue Wu ◽  
Yao Chen ◽  
Chuanfei Hu ◽  
Dong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Monoclonal Antibodies ◽  
Treatment Group ◽  
Tumor Growth ◽  
Combined Treatment ◽  
Proliferation Index ◽  
Bifidobacterium Infantis ◽  
Glut 1 ◽  
Pet Ct ◽  
Tnf Α

Abstract Background：The hypoxic microenvironment of solid tumors reduces the susceptibility of cancer cells to radiotherapy. Current treatments are focused on the development of anti-cancer agents that selectively target tumor cells with no toxicity to healthy tissue. Bacteria colonize and destroy tumors and have emerged as biological vectors that can survive in the tumor microenvironment. Methods：In this study, a Lewis lung carcinoma transplant mouse model was established and treated with a combination of bifidobacterium infantis (Bi), its specific monoclonal antibodies (Ab) and radiotherapy (RT). 18F-FDG PET/CT and 18F-FMISO PET/CT imaging were performed to monitor tumor growth and hypoxia in the tumor tissue. Phosphorylated histone (γ-H2AX), the proliferation index (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (Glut-1) levels were assessed through immunohistochemistry. Results：The results showed that the combined treatment group (Ab+ Bi+ RT) displayed delayed tumor growth and prolonged the survival of mice. The combined treatment group also had lower levels of HIF-1α, Glut-1, and CD31 expression, and a lower uptake of FDG and FMISO. The tumors treated with the combination therapy also had lower levels of hypoxia, and increased γ-H2AX and TNF-α expression. Conclusion：Taken together, these data suggest that the combination of bifidobacterium infantis and its specific monoclonal antibodies can markedly improve the efficacy of radiotherapy for the treatment of lung cancer.

scholarly journals EXTH-52. CO-TARGETING ONCOSTATIN M RECEPTOR USING MONOCLONAL ANTIBODIES IN COMBINATION WITH PRESENT STANDARDS OF CARE FOR GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi93-vi93
Author(s):  
Audrey Burban ◽  
Ahmad Sharanek ◽  
Arezu Jahani-Asl
Keyword(s):  
Stem Cells ◽  
Monoclonal Antibodies ◽  
Tumor Growth ◽  
Standard Of Care ◽  
Adult Brain ◽  
Oncostatin M ◽  
Standards Of Care ◽  
Surgical Removal ◽  
Current Standard ◽  
Therapeutic Monoclonal Antibodies

Abstract Glioblastoma Multiform (GBM) is the most aggressive primary tumor in the adult brain. The present standard of care includes surgical removal of the tumors followed by treatment with Temozolomide (TMZ) and radiation therapy. Despite intense efforts and advances in surgery and combination therapy, the median survival rate for GB patients remain 16 months following diagnosis. EGFRvIII/STAT3 signaling plays critical roles in GBM pathogenesis. We have recently discovered that the tumorigenic capacity of EGFRvIll/STAT3 pathway crucially depends on the cytokine receptor for Oncostatin M (OSMR). OSMR is a required co-receptor of EGFRvIII and a direct transcriptional target of STAT3. Strikingly, OSMR is highly expressed in brain tumor stem cells (BTSCs), a population of self-renewing malignant stem cells within GBM that contribute to tumor growth, recurrence and therapeutic resistance. We have generated therapeutic monoclonal antibodies against OSMR (OSMR mAb) that function as powerful inhibitors of OSMR. Treatment of BTSCs with OSMR mAb resulted in inhibition of OSMR-mediated signaling pathways and significantly impaired the phosphorylation of STAT3. Strikingly, treatment of BTSCs with OSMR mAb significantly attenuated BTSC self-renewal in limiting dilution assay and sensitized their response to tyrosine kinase inhibitors (TKI), ionizing radiation and TMZ. Using patient derived stem cell tumor xenografts, we have shown that OSMR mAb significantly reduced tumor growth compared to IgG control. Together, our findings suggest that targeting OSMR using therapeutic monoclonal antibodies in combination with EGFR inhibitors and/ or the current standard of care may provide a promising therapeutic strategy for glioblastoma.

scholarly journals Mouse plasmacytoma growth in vivo: enhancement by interleukin 6 (IL-6) and inhibition by antibodies directed against IL-6 or its receptor.

1990 ◽  
Vol 172 (3) ◽  
pp. 997-1000 ◽  
Author(s):  
A Vink ◽  
P Coulie ◽  
G Warnier ◽  
J C Renauld ◽  
M Stevens ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Growth ◽  
Cell Line ◽  
Interleukin 6 ◽  
Essential Role ◽  
Expression Vector ◽  
Tumor Challenge ◽  
Present Evidence

Murine plasmacytomas show a striking dependence on interleukin 6 (IL-6) for their growth in vitro. Here, we present evidence suggesting that IL-6 also plays an essential role in the in vivo development of these tumors. This conclusion is based on the finding that the tumorigenicity of an IL-6-dependent plasmacytoma cell line was increased approximately 100-fold on transfection with an IL-6 expression vector, whereas it was inhibited in animals treated with monoclonal antibodies capable of blocking the binding of IL-6 to its receptor. Injection of these antibodies 1 d before tumor challenge protected greater than 50% of the mice and retarded tumor growth in all animals. Tumors arising in antibody-treated mice retained their IL-6 dependence in vitro, suggesting that the level of protection could be improved if stronger IL-6 antagonists were available.

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