The Anti-Idiotypic Approach to Active Specific Immunotherapy of Malignant Melanoma

Wang, Xinhui; Desai, Smruti; Noronha, Elvyra J.; Mittelman, Abraham; Ferrone, Soldano

doi:10.1016/b978-044482807-1/50050-8

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…The proteins from the radiolabeled cell lysate 1 were then resolved on a reducing 10% Tris-HCl SDS-polyacrylamide gel. The radioactive protein that was immunoprecipitated was detected by autoradiography by exposing dry gel to film for 24 h at -80jC (27).…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Putative Ovarian Oncogene, Elongation Factor 1α, Isolated by Panning a Synthetic Phage Display Single-Chain Variable Fragment Library with Cultured Human Ovarian Cancer Cells

Sharma¹,

Tammela²,

Wang³

et al. 2007

Clinical Cancer Research

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Purpose: In an effort to identify cell surface targets and single short-chain antibody (scFv) for ovarian cancer therapy, we used a phage display approach to isolate an antibody with high reactivity against ovarian cancer. Experimental Design: A phage scFv library was subjected to panning against human SK-OV-3 ovarian cancer cells. A clone with high reactivity was selected and tested in immunoperoxidase staining on a panel of normal tissues and ovarian carcinoma. Using immunoprecipitation, a differentially expressed band was analyzed by mass spectrometry. The antigen subclass was characterized with reverse transcription-PCR on cDNA library of normal tissues, and 91 ovarian cancer specimens, and correlated with clinicohistopathologic characteristics. Results: Ninety-six individual scFv clones were screened in ELISA following panning. scFv F7 revealed high reactivity with ovarian cancer cell lines and showed intense staining of 15 fresh ovarian cancer specimens and no staining of a panel of normal tissues. A 40-kDa protein was identified to be translation elongation factor 1a1 (EEF1A1; P < 0.05). The expression of EEF1A2, a highly homologous and functionally similar oncogene, was found to be restricted only to the normal tissues of the heart, brain, and skeletal muscle. Aberrant EEF1A2 mRNA expression was found in 21of 91 (23%) of ovarian cancer specimens and significantly correlated with increased likelihood of recurrence (P = 0.021). Conclusions: scFv F7 may represent an ovarian cancer^specific antibody against translation EEF1A family of translational factors. We propose that EEF1A2 may be a useful target for therapy of human ovarian cancer.Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer deaths in the United States (1). Although it is clear that most patients with EOC will respond to platinum-and paclitaxel-based chemotherapy, including complete responses, the relapse rate within 2 years is f85% (2). Once relapse occurs, there is no known curative therapy and management becomes primarily palliative. Thus, there is a need to develop additional therapeutic approaches for the management of this disease. A proposed strategy for minimizing the risk of recurrent disease is immunotherapy. Patients who show complete response to frontline surgery and chemotherapy could be considered for immunotherapy, with the presumption that the majority do in fact have micrometastases. The development of successful immunotherapeutic or targeted therapy strategies requires the identification and characterization of ovarian tumor -associated antigens that will be recognized by the host immune system, leading to tumor rejection. Therefore, there is a need to identify and characterize novel antigens that may be useful for immunotherapy approach against this cancer (3).Antibody therapy has long been sought after as a treatment strategy in cancer care. The classic approach to obtain tumorspecific antibodies has been to immunize mice with tumor cells and to screen the mouse serum for antibodies for their ...

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Section: Methodsmentioning

confidence: 99%

Characterization of a Putative Ovarian Oncogene, Elongation Factor 1α, Isolated by Panning a Synthetic Phage Display Single-Chain Variable Fragment Library with Cultured Human Ovarian Cancer Cells

Sharma¹,

Tammela²,

Wang³

et al. 2007

Clinical Cancer Research

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Intravenous Immunoglobulin-Based Immunotherapy: an Arsenal of Possibilities for Patients and Science

2009

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The use of intravenous immunoglobulin (IVIG) concentrated from pooled healthy donors' plasma has gained increasing popularity. IVIG therapy has become important as a replacement therapy in primary and acquired humoral immunodeficiencies, and it has been extended to autoimmune, neurodegenerative and inflammatory conditions and transplantation therapy. Recurrent pregnancy failure and cancer are rather new platforms, where IVIG has shown its beneficial effects. This manuscript is focused on these two off-labelled usages. The immunomodulatory mechanisms of IVIG therapy appear as a coordinated orchestration of different functions, resulting in a synergistic effect. Treatment monitoring and detailed molecular analyses reveal how such treatments may interfere with disease pathogenesis. These finding may foster the development of novel therapeutic and/or preventive strategies. Studying this field with bidirectional bench-to-bedside and bedside-to-bench approaches fit well into 'the two-way road' paradigm of translational medicine.

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Limited Diversity of Human scFv Fragments Isolated by Panning a Synthetic Phage-Display scFv Library with Cultured Human Melanoma Cells

Noronha

Wang²,

Desai³

et al. 1998

The Journal of Immunology

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To broaden the specificity of the Abs recognizing human melanoma-associated Ags (MAAs), we have isolated human single-chain fragment of the V region (scFv) fragments by panning the synthetic phage Ab library (#1) with the human melanoma cell lines S5 and SK-MEL-28. All of the isolated scFv fragments reacted with the mouse mAb defined high molecular weight melanoma-associated Ag (HMW-MAA). scFv #70 immunoprecipitates the two characteristic subunits of HMW-MAA, while scFv #28 only immunoprecipitates its large subunit. These results challenge the current view regarding the structure of HMW-MAA and indicate that it consists of two independent subunits. The human scFv fragments share some similarities with the mouse anti-HMW-MAA mAb. Like mAb 149.53 and 225.28, scFv #28 reacts with rat B49 neural cells that express a homologue of HMW-MAA. scFv #70 reacts with a determinant that is spatially close to the one identified by mAbs 149.53, VT68.2, and VT86. Besides suggesting similarities in the recognition of human melanoma cells by the mouse and human Ab repertoire, these results indicate that the Abs isolated from synthetic Ab libraries resemble those that are found in natural Ab repertoires. The restricted diversity of the scFv fragments that were isolated by panning synthetic Ab libraries with different melanoma cell lines suggests that certain Ags, like HMW-MAA, are immunodominant in vitro. This phenomenon, which parallels the in vivo immunodominance of certain Ags, implies that the antigenic profile of the cells used for panning determines the specificity of the preponderant population of isolated Abs.

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The Anti-Idiotypic Approach to Active Specific Immunotherapy of Malignant Melanoma

Cited by 3 publications

References 32 publications

Characterization of a Putative Ovarian Oncogene, Elongation Factor 1α, Isolated by Panning a Synthetic Phage Display Single-Chain Variable Fragment Library with Cultured Human Ovarian Cancer Cells

Characterization of a Putative Ovarian Oncogene, Elongation Factor 1α, Isolated by Panning a Synthetic Phage Display Single-Chain Variable Fragment Library with Cultured Human Ovarian Cancer Cells

Intravenous Immunoglobulin-Based Immunotherapy: an Arsenal of Possibilities for Patients and Science

Limited Diversity of Human scFv Fragments Isolated by Panning a Synthetic Phage-Display scFv Library with Cultured Human Melanoma Cells

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