Selection of anti-cancer antibodies from combinatorial libraries by whole-cell panning and stringent subtraction with human blood cells

Siva, Amara C.; Kirkland, Richard; Lin, Bing; Maruyama, Toshiaki; McWhirter, John R.; Yantiri-Wernimont, Ferda; Bowdish, Katherine S.; Xin, Hong

doi:10.1016/j.jim.2007.11.008

Cited by 30 publications

(35 citation statements)

References 23 publications

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“…T2 cells were pulsed with the GVL or KIFS peptides at 20 mg/ml for 4 h in AIM-V growth medium as described previously (20,21,27).…”

Section: T2 Stainingmentioning

confidence: 99%

“…The demonstration that Abs can act as effective therapies for cancer has raised significant interest in identifying tumor-specific biomarkers. Unfortunately, only a limited number of tumor-specific markers expressed uniquely on the surface of tumor cells have been discovered, spurring increased efforts to identify new cancer cell-specific markers for therapeutic Ab targeting in oncology (25)(26)(27)(28).…”

mentioning

confidence: 99%

“…We reported previously on a TCRm Ab-specific for peptide GVLPALPQV derived from human chorionic gonadotropin (hCG)-b and presented by HLA-Ap0201 (27). In a comprehensive review of hCG in cancer, Stenman et al (42) reported hCGb in the serum of 45-60% of patients with biliary and pancreatic cancers and 10-30% of other cancers.…”

mentioning

confidence: 99%

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TCR Mimic Monoclonal Antibody Targets a Specific Peptide/HLA Class I Complex and Significantly Impedes Tumor Growth In Vivo Using Breast Cancer Models

Verma

Neethling²,

Caseltine³

et al. 2010

The Journal of Immunology

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Our laboratory has developed a process for generating mAbs with selectivity to unique peptides in the context of MHC molecules. Recently, we reported that RL4B, an mAb that we have called a TCR mimic (TCRm) because it recognizes peptide in the context of MHC, has cytotoxic activity in vitro and prevented growth of tumor cells in a prophylactic setting. When presented in the context of HLA-A2, RL4B TCRm recognizes the peptide GVLPALPQV derived from human chorionic gonadotropin (hCG)-β. In this study, we show that RL4B TCRm has strong binding affinity for the GVLPALPQV peptide/HLA-A2 epitope and fine binding specificity for cells that express endogenous hCGβ Ag and HLA-A2. In addition, suppression of tumor growth with RL4B TCRm was observed in orthotopic models for breast cancer. Using two aggressive human tumor cell lines, MDA-MB-231 and MCF-7, we provide evidence that RL4B TCRm significantly retards tumor growth, supporting a possible role for TCRm agents in therapeutic settings. Moreover, tumors in mice responded to RL4B TCRm therapy in a dose-dependent manner, eliminating tumors at the highest dose. RL4B TCRm strongly detects the hCGβ peptide/HLA-A2 epitope in human primary breast tumor tissue, but does not react or reacts weakly with normal breast tissue from the same patient. These results further illustrate the selective nature of TCRm Abs and the clinical relevance of the GVLPALPQV peptide/HLA-A2 epitope expression in tumor cells, because they provide the first evidence that Abs that mimic the TCR can be used to markedly reduce and suppress tumor growth.

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“…T2 cells were pulsed with the GVL or KIFS peptides at 20 mg/ml for 4 h in AIM-V growth medium as described previously (20,21,27).…”

Section: T2 Stainingmentioning

confidence: 99%

mentioning

confidence: 99%

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TCR Mimic Monoclonal Antibody Targets a Specific Peptide/HLA Class I Complex and Significantly Impedes Tumor Growth In Vivo Using Breast Cancer Models

Verma

Neethling²,

Caseltine³

et al. 2010

The Journal of Immunology

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“…Although most previous studies have used non-fixed living cells as the targets to screen for cancer cell antibodies (7,19,20), some researchers still prefer to use PFA fixed cells to screen for antibodies. Fixed cells ensure the integrity of the cell membrane during the entire process (21,22), decrease cell breakage and antigen degradation and avoid the inhibition of bacterial growth caused by hydrolytic enzymes and other harmful substances released by the breakdown of residual cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Screening for antibodies against intact cancer cells with a naï¿½ve large phage antibody library

Zhou²,

Wang³

et al. 2011

Int J Mol Med

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Abstract. Large phage antibody libraries are expected to be an efficient technology for obtaining humanized anti-tumor antibodies. However, few reports have been concerned about the selection strategies for intact cancer cells as targets. In this study, a 2x1011 large naïve scFv library from blood B lymphocytes of normal adult donors and neonatal cord blood was constructed using the LoxP-cre system. Three human esophageal cancer cell lines were equally mixed for use as the target. These intact cells were divided into two groups, PF and NF, according to the treatment method of the cells (fixed with 2% PFA or not, respectively). Positive phage antibodies were identified following 4 panning cycles of adhesion, elution and amplification. Using a cell ELISA assay, it was found that the additional procedure of directly infecting XL1-Blue bacteria with the cell pellet following washing with an acidic solution can effectively decrease the loss of positive phage, yielding a positive screening rate of 11.6% (61/525). Most of the phage antibodies displayed binding activity with all three esophageal cancer cell lines. Moreover, other phages (such as NFc53a and NFc70a) appeared to be specific for certain cell lines. Regarding the method used to treat the target cells, both the positive screening rate and the genetic diversity of the antibody variable region were significantly higher in the NF group (12.9 and 71.4%, respectively) than in the PF group (10.5 and 14.2%, respectively). Immunohistochemical analysis demonstrated that the scFv phages have good specificity for esophageal cancer. This technology is helpful for developing small molecular tracers and targeted therapies for malignant tumors.

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“…The notion that CDCP1 can be targeted to disrupt cancer processes has recently been tested using an anti-CDCP1 monoclonal antibody generated from a phage displayed combinatorial antibody library (16). In vitro, this antibody inhibited prostate cancer PC-3 cell migration and invasion (17).…”

Section: Cdcp1 Supports Cancer Progression In Model Systemsmentioning

confidence: 99%

The cell surface glycoprotein CDCP1 in cancer—Insights, opportunities, and challenges

Wortmann

Deryugina

et al. 2009

IUBMB Life

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SummaryIn the last few years dysregulated expression of the cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) has been associated with several cancers and this cell surface molecule has been recognized both as a tumor marker and as a potential target to disrupt progression of cancer. Here we summarize what is known about CDCP1 including its structural features, expression in normal and cancerous tissues, and the in vitro experiments and studies in animal models that have provided the key insights into its potential role in tumor formation and metastasis in humans. We conclude by highlighting opportunities and challenges in targeting CDCP1 in cancer.2009 IUBMB IUBMB Life, 61(7): [723][724][725][726][727][728][729][730] 2009

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Selection of anti-cancer antibodies from combinatorial libraries by whole-cell panning and stringent subtraction with human blood cells

Cited by 30 publications

References 23 publications

TCR Mimic Monoclonal Antibody Targets a Specific Peptide/HLA Class I Complex and Significantly Impedes Tumor Growth In Vivo Using Breast Cancer Models

TCR Mimic Monoclonal Antibody Targets a Specific Peptide/HLA Class I Complex and Significantly Impedes Tumor Growth In Vivo Using Breast Cancer Models

Screening for antibodies against intact cancer cells with a naï¿½ve large phage antibody library

The cell surface glycoprotein CDCP1 in cancer—Insights, opportunities, and challenges

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