Antibody-based therapeutics: Focus on prostate cancer

Ross, Jeffrey S.; Gray, Karen; Webb, Iain J.; Gray, Gary S.; Rolfe, Mark; Schenkein, David P.; Nanus, David M.; Millowsky, Mathew I.; Bander, Neil H.

doi:10.1007/s10555-005-6194-0

Cited by 40 publications

(23 citation statements)

References 72 publications

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“…Traditional approaches to cancer therapy involve surgery, radiation therapy, and chemotherapy. More recent efforts target specific biochemical mechanisms that are essential for the survival of cancer cells, such as apoptotic pathways (1,30,31). Using antibodies to affect tumor cell growth and survival has been one of the applications for monoclonal antibodies.…”

Section: Discussionmentioning

confidence: 99%

Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis

Misra

Mowery

Kaczowka

et al. 2009

Molecular Cancer Therapeutics

134

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Binding of activated α 2 -macroglobulin to GRP78 on the surface of human prostate cancer cells promotes proliferation by activating signaling cascades. Autoantibodies directed against the activated α 2 -macroglobulin binding site in the NH 2 -terminal domain of GRP78 are receptor agonists, and their presence in the sera of cancer patients is a poor prognostic indicator. We now show that antibodies directed against the GRP78 COOH-terminal domain inhibit [3 H]thymidine uptake and cellular proliferation while promoting apoptosis as measured by DNA fragmentation, Annexin V assay, and clonogenic assay. These antibodies are receptor antagonists blocking autophosphorylation and activation of GRP78. Using 1-LN and DU145 prostate cancer cell lines and A375 melanoma cells, which express GRP78 on their cell surface, we show that antibodies directed against the COOH-terminal domain of GRP78 up-regulate the tumor suppressor protein p53. By contrast, antibody directed against the NH 2

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Section: Discussionmentioning

confidence: 99%

Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis

Misra

Mowery

Kaczowka

et al. 2009

Molecular Cancer Therapeutics

134

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“…In addition, toxin-conjugated anti-PSCA antibody completely eradicated established tumors (23). For other novel prostate cancer targets, such as PSMA and tomoregulin, naked mAb efficacy has not been shown, resulting in the need to use mAbs as a vehicle to deliver payloads, such as radioisotopes and toxins, to affect tumor growth (24)(25)(26). The strong and homogeneous expression of STEAP-1 in cancer specimens, together with its restricted expression in normal tissues, also makes it a suitable target for antibody drug conjugate therapy.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo

Challita-Eid¹,

Morrison²,

Etessami³

et al. 2007

Cancer Research

110

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Six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) is a novel cell surface protein highly expressed in primary prostate cancer, with restricted expression in normal tissues. In this report, we show STEAP-1 expression in prostate metastases to lymph node and bone and in the majority of human lung and bladder carcinomas. We identify STEAP-1 function in mediating the transfer of small molecules between adjacent cells in culture, indicating its potential role in tumor cell intercellular communication. The successful generation of two monoclonal antibodies (mAb) that bind to cell surface STEAP-1 epitopes provided the tools to study STEAP-1 susceptibility to naked antibody therapy. Both mAbs inhibited STEAP-1-induced intercellular communication in a dosedependent manner. Furthermore, both mAbs significantly inhibited tumor growth in mouse models using patientderived LAPC-9 prostate cancer xenografts and established UM-UC-3 bladder tumors. These studies validate STEAP-1 as an attractive target for antibody therapy in multiple solid tumors and provide a putative mechanism for mAb-induced tumor growth inhibition. [Cancer Res 2007;67(12):5798-805]

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“…Peptides targeting the extracellular portion of PSMA have recently been identified from a phage display library and have been shown to possess micromolar (Amol/L) binding affinities to the extracellular portion of the receptor (32). In addition, aptamers (40)(41)(42) and monoclonal antibodies (43,44) have also been used to target the PSMA receptor.…”

Section: Discussionmentioning

confidence: 99%

Amphipathic Peptide-Based Fusion Peptides and Immunoconjugates for the Targeted Ablation of Prostate Cancer Cells

et al. 2007

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We describe the design, generation, and in vitro evaluation of targeted amphipathic fusion peptides and immunoconjugates for the ablation of prostate cancer cells. The overexpression of the prostate-specific membrane antigen (PSMA) was exploited as means to specifically deliver cytotoxic peptides to prostate cancer cells. Cationic amphipathic lytic peptides were chosen as cytotoxic agents due to their ability to depolarize mitochondrial membranes and induce apoptosis. Specific delivery of the lytic peptide was facilitated by PSMA-targeting peptides and antibodies. Our results indicate that although the use of PSMA-targeted peptides only modestly enhanced the cytotoxic activity of the lytic peptide, peptide-antibody conjugates were two orders of magnitude more potent than untargeted peptide. In addition to quantifying the cytotoxic activities of the individual constructs, we also investigated the mechanisms of cell death induced by the fusion peptides and immunoconjugates. Although fusion peptides induced oncotic/necrotic death in cells, treatment with immunoconjugates resulted in apoptotic death. In summary, immunoconjugates based on lytic peptides are a promising class of therapeutics for prostate cancer therapy and warrant further investigation. [Cancer Res 2007;67(13):6368-75]

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Antibody-based therapeutics: Focus on prostate cancer

Cited by 40 publications

References 72 publications

Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis

Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis

Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo

Amphipathic Peptide-Based Fusion Peptides and Immunoconjugates for the Targeted Ablation of Prostate Cancer Cells

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