A3—a novel colon and pancreatic cancer reactive antibody from a primate phage library selected using intact tumour cells

Tordsson, Jesper; Lavasani, Shahram; Ohlsson, Lennart; Karlström, Pia; Svedberg, Helena; Abrahmsén, Lars; Brodin, Thomas

doi:10.1002/1097-0215(20000815)87:4<559::aid-ijc16>3.0.co;2-#

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…However, the mechanism for immunological tumor regression has not been well evaluated and improvement of the immunotherapy has been difficult partly because only a limited number of tumor antigens have so far been identified for pancreatic cancer. 16,17 Furthermore, additional tumor markers are required for better diagnosis of pancreatic cancer. Thus, identification of additional antigens is important for development of immunotherapy and diagnostic methods for patients with pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Okada

Noji

Goto

et al. 2005

Intl Journal of Cancer

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To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD41 helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM. ' 2005 Wiley-Liss, Inc.Key words: SEREX; tumor antigens; pancreatic cancer; DNA mismatch repair enzyme Early diagnosis and curative treatment are still difficult for pancreatic ductal adenocarcinoma despite of increased incidence rate.

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Section: Discussionmentioning

confidence: 99%

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Okada

Noji

Goto

et al. 2005

Intl Journal of Cancer

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“…Many groups have used immunised libraries to generate scFv antibodies. [20][21][22] This methodology has several advantages over traditional hybridoma technology; in particular, the ease of screening large numbers of clones, meaning that the selected scFv are often of higher affinity. Kits are now available, such as the ''RPAS mouse scFv module'' from Amersham Pharmacia Biotech (Little Chalfont, Buckinghamshire, UK), that can be used to generate scFv repertoires from mouse spleen or hybridoma cells.…”

Section: Recombinant Phage Technologymentioning

confidence: 99%

Demystified… recombinant antibodies

Smith

2004

J Clin Pathol

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Recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic/therapeutic reagents. In this article, a background to humanised antibodies is given, together with details of the generation of antibody fragments—for example, single chain Fv fragments. Phage antibody fragments are fast becoming popular and can be generated by simple established methods of affinity enrichment from libraries derived from immune cells. Phage display methodology can also be used for the affinity enrichment of existing antibody fragments to provide a reagent with a higher affinity. Here, phage antibodies are demystified to provide a greater understanding of the potential of these reagents and to engage clinicians and biomedical scientists alike to think about potential applications in pathology and clinical settings.

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“…This mutant created by Dohlsten's group displayed a 1,000-fold reduction in major histocompatibility complex class (MHC) II binding to reduce systemic toxicity [6] and was consequently conjugated with antibodies as a powerful CTL inducer against cancer [6], [12], [13]. These fusion protein or antibodies fused with unmutant SEA [4], [5], [14], [15] inhibited blood carcinomas and metastases.…”

Section: Introductionmentioning

confidence: 99%

Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein

et al. 2011

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Successful immune-mediated regression of solid tumors is difficult because of the small number of cytotoxic T lymphocytes (CTLs) that were traffic to the tumor site. Here, the targeting of tumor-specific infiltrating CTLs was dependent on a fusion protein consisting of human epidermal growth factor (EGF) and staphylococcal enterotoxin A (SEA) with the D227A mutation. EGF-SEA strongly restrained the growth of murine solid sarcoma 180 (S180) tumors (control versus EGF-SEA, mean tumor weight: 1.013 versus 0.197 g, difference = 0.816 g). In mice treated with EGF-SEA, CD4+, CD8+ and SEA-reactive T lymphocytes were enriched around the EGFR expressing tumor cells. The EGF receptors were potentially phosphorylated by EGF-SEA stimulation and the fusion protein promoted T cells to release the tumoricidal cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Intratumoral CTLs secreted cytolytic pore-forming perforins and granzyme B proteins near the surface of carcinomas, causing the death of many tumor cells. We additionally show that labeled EGF-SEA was directly targeted to the tumor tissue after intravenous (i.v.) injection. The findings demonstrate that antibody-like EGF-SEA plays an important role in arresting CTLs in the solid tumor site and has therapeutic potential as a tumor-targeting agent.

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A3—a novel colon and pancreatic cancer reactive antibody from a primate phage library selected using intact tumour cells

Cited by 8 publications

References 35 publications

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Demystified… recombinant antibodies

Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein

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