Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

Pavoni, Emiliano; Monteriù, Giorgia; Santapaola, Daniela; Petronzelli, Fiorella; Anastasi, Anna Maria; Pelliccia, Angela; D'Alessio, Valeria; Santis, Rita De; Minenkova, Olga

doi:10.1186/1472-6750-7-70

Cited by 59 publications

(42 citation statements)

References 41 publications

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“…In future, we will examine whether such autoantibodies exist in the sera of HCC patients. Pavoni et al showed that breast tumor tissues containing B cells are an efficient source for constructing phage display libraries [20]. Based on their results, we constructed a library derived from HCC patient tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Reasonably, the phage library derived from B cells of tumor patients can provide antibody fragments against specific tumor antigens. Pavoni et al reported that high-affinity phage clones against tumor antigens are isolated using a library derived from the peripheral blood cells of breast tumor patients [20]. In this study, we attempted to produce a human scFv specific for Lu using phage libraries displaying scFv derived from HCC patients.…”

Section: Introductionmentioning

confidence: 99%

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An Anti-Human Lutheran Glycoprotein Phage Antibody Inhibits Cell Migration on Laminin-511: Epitope Mapping of the Antibody

et al. 2017

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The Lutheran glycoprotein (Lu), also known as basal cell adhesion molecule (B-CAM), is an Ig superfamily (IgSF) transmembrane receptor for laminin α5. Although Lu is not present in normal hepatocytes, its expression is significantly increased in hepatocellular carcinoma (HCC). In this study, we isolated thirteen phage antibodies to Lu from a phage library of peripheral blood from HCC patients, suggesting that these patients produced autoantibodies against endogenous Lu. To characterize the phage antibodies, we determined the Lu domains they recognize. The extracellular domain of Lu contains five IgSF domains, D1-D2-D3-D4-D5. The epitope of one phage antibody (A7) was localized to the D5 domain. The other phage antibodies recognized the D2 domain, which is also recognized by a function blocking mouse monoclonal antibody. One of the antibodies to D2 (C7) inhibited the binding of Lu to ligand, and it also prevented tumor cell migration on laminin-511 (LM-511). However, the C7 scFv purified from the periplasm fraction of bacteria did not exhibit the inhibitory effects, indicating that the scFv form could not sterically inhibit the binding of Lu to LM-511. We also identified the amino acid residues that form the epitope recognized by the C7 phage antibody. Mutagenesis studies showed that Arg247 is necessary for forming the epitope. The C7 phage antibody and its epitope may be useful for developing drugs to prevent HCC progression and/or metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Anti-Human Lutheran Glycoprotein Phage Antibody Inhibits Cell Migration on Laminin-511: Epitope Mapping of the Antibody

et al. 2017

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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 pathology of breast cancer has been shown to be associated with alterations of different components of body's immune machinery (78)(79)(80)(81). It has been recently proposed that inflammation, in part due to tumor-associated macrophages and proinflammatory cytokines, may promote more aggressive ER-positive tumors and the suggested treatment includes targeting inflammation combined with anti-estrogenic drugs (82).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effects of anti-estrogenic drugs

Ray¹,

M²

2012

Acta Pharmaceutica

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Immunomodulatory effects of anti-estrogenic drugsThere are substantial experimental, epidemiological and clinical evidences that show that breast cancer pathology is influenced by endogenous estrogens. This knowledge is the foundation upon which endocrine deprivation therapy has been developed as a major modality for the management of breast cancer. Tamoxifen, which functions as a competitive partial agonist-inhibitor of estrogen at its receptor, has been widely used for more than three decades for adjuvant endocrine treatment in breast cancer. Currently, other effective drugs for endocrine therapy include raloxifene, different aromatase inhibitors (particularly third-generation agents) and luteinizing hormone-releasing hormone agonists. In recent years, a growing body of evidence suggests that these drugs can also act as immune modulators by altering the function of various leukocytes and the release of different cytokines. Moreover, there is evidence that anti-estrogens may prove to be beneficial in the treatment or prevention of some autoimmune diseases due to their effects on immune function. However, their immunopharmacological aspects in the present state of knowledge are not precisely comprehensible. Only a clear pathophysiological understanding could lead to an efficient strategy for breast cancer prevention and decrease in the mortality due to this disease.

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Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

Cited by 59 publications

References 41 publications

An Anti-Human Lutheran Glycoprotein Phage Antibody Inhibits Cell Migration on Laminin-511: Epitope Mapping of the Antibody

An Anti-Human Lutheran Glycoprotein Phage Antibody Inhibits Cell Migration on Laminin-511: Epitope Mapping of the Antibody

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

Immunomodulatory effects of anti-estrogenic drugs

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