Hodgkin's Disease

DeVita, V. T.

doi:10.1016/s0140-6736(71)90032-8

Cited by 10 publications

(14 citation statements)

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“…In conclusion, repeated 90 Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients. T reatment with combination chemotherapy, radiation, and hematopoietic stem cell transplantation has increased the disease-free survival in Hodgkin's lymphoma (HL) from less than 5% in 1963 to more than 80% at present (1)(2)(3)(4)(5)(6). Recently the US Food and Drug Administration approved brentuximab vedotin for the treatment of relapsed HL (7).…”

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confidence: 99%

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Janik

Morris

O’Mahony

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody 90 Y-daclizumab. 90 Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with 90 Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25 − provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated 90 Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.T reatment with combination chemotherapy, radiation, and hematopoietic stem cell transplantation has increased the disease-free survival in Hodgkin's lymphoma (HL) from less than 5% in 1963 to more than 80% at present (1-6). Recently the US Food and Drug Administration approved brentuximab vedotin for the treatment of relapsed HL (7). Furthermore the anti-PD1 agent pembrolizumab has shown promising results in classic HL (8). Nevertheless, a significant fraction of patients do not respond to treatment or subsequently relapse. To date more than 30 different mAb preparations directed toward antigens expressed by malignant Reed-Sternberg cells have been studied (6). These include mAbs linked to drugs or toxins targeting CD25 or CD30 expressed on Reed-Sternberg cells (6-11). Brentuximab vedotin, an anti-CD30 antibody drug conjugate, has induced a significant number of responses in refractory HL (7, 11). Although other antibody immunotoxins have demonstrated some clinical efficacy, they have yielded few complete responses (CRs) (6, 9, 10). An alternative strategy has been to arm mAbs with radionuclides. Radioimmunotherapy using 90 Y-anti-ferritin and 131 I-anti-CD30 antibodies has resulted in partial (PRs) and CRs in HL (12-15). Deficiencies with these approaches reflect the lack of tumor specificity of ferritin-targ...

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confidence: 99%

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Janik

Morris

O’Mahony

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Anti-CD20 antibodies, such as rituximab, for example, bind exclusively to mature B lymphocytes, resulting in the depletion of B cells. Because CD20 is neither detectable on any other normal cell type nor shared by the stem cell precursor of the B-cell lineage (13,14), there is no severe dose-limiting toxicity, and normal B-lymphocyte levels are eventually restored by target-negative stem cells. Importantly, even malignant B cells that express CD20 at much lower levels than nonneoplastic B cells can be treated successfully with rituximab.…”

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confidence: 99%

Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development

Şahin

Koslowski²,

Dhaene³

et al. 2008

Clinical Cancer Research

279

285

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Purpose: Antibody-based cancer therapies have emerged as the most promising therapeutics in oncology. The purpose of this study was to discover novel targets for therapeutic antibodies in solid cancer. Experimental Design:We combined data mining and wet-bench experiments to identify strictly gastrocyte lineage^specific cell surface molecules and to validate them as therapeutic antibody targets. Results: We identified isoform 2 of the tight junction molecule claudin-18 (CLDN18.2) as a highly selective cell lineage marker. Its expression in normal tissues is strictly confined to differentiated epithelial cells of the gastric mucosa, but it is absent from the gastric stem cell zone. CLDN18.2 is retained on malignant transformation and is expressed in a significant proportion of primary gastric cancers and the metastases thereof. In addition to its orthotopic expression, we found frequent ectopic activation of CLDN18.2 in pancreatic, esophageal, ovarian, and lung tumors, correlating with distinct histologic subtypes. The activation of CLDN18.2 depends on the binding of the transcription factor cyclic AMP^responsive element binding protein to its unmethylated consensus site. Most importantly, we were able to raise monoclonal antibodies that bind to CLDN18.2 but not to its lung-specific splice variant and recognize the antigen on the surface of cancer cells. Conclusions: Its highly restricted expression pattern in normal tissues, its frequent ectopic activation in a diversity of human cancers, and the ability to specifically target this molecule at the cell surface of tumor cells qualify CLDN18.2 as a novel, highly attractive pan-cancer target for the antibody therapy of epithelial tumors.Gastroesophageal and pancreatic cancers are among the malignancies with the highest unmet medical needs (1). Gastric cancer is the second leading cause of cancer death worldwide. In 2002, f1.4 million people worldwide developed gastroesophageal cancers and 1.1 million died (2). Esophageal cancer incidence has increased in recent decades, coinciding with a shift in histologic type and primary tumor location. Adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and Western Europe, with most tumors located in the distal esophagus (3).The overall 5-year survival rates for gastroesophageal cancers are 20% to 25% despite the aggressiveness of established standard treatments associated with substantial side effects (4, 5). For pancreatic cancer, there is an even greater medical need. Due to the advanced state of the disease at the time of diagnosis, the prognosis is extremely poor, with median survival times of less than 6 months and a 5-year survival rate of <5.5%. The lack of a major benefit from the various newergeneration combination chemotherapy regimens for these cancers has stimulated research into the use of targeted agents, such as small molecule -based kinase inhibitors and monoclonal antibodies (mAb; ref. 6). However, mAbs, such as bevacizumab, cetuximab, and trastuzumab...

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“…The disease presents histologically as a heterogeneous population of lymphoid and inflammatory cells with a minority of malignant Reed-Sternberg (RS) cells (and/or variants) scattered throughout the tissue. 1,6 The presence of RS cells and their variants is not pathognomonic of the disease but is essential for a histopathologic diagnosis.…”

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Feline Hodgkin's-like Lymphoma: 20 Cases (1992–1999)

Walton

Hendrick

2001

Vet Pathol

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Abstract. We identified 20 cases of feline lymphadenopathy that conform to many clinical and histologic manifestations of human Hodgkin's disease. Histologic subtypes encountered included lymphocyte predominance (nine cases), mixed cellularity (nine cases), and nodular sclerosis (two cases). Two cases were not easily classified; fibrous bands were present, but the absence of nodules supported a subclassification of mixed cellularity Hodgkin's disease. Immunohistochemical staining of the tissues using antibodies against the pan T-cell antigen CD3, the human B-lymphocyte antigen 36 (BLA.36), the pan B-lymphocyte and plasma cell marker CD79a, and a myeloid antigen (MAC387) confirmed the phenotypic heterogeneity of the tumor. Classic ReedSternberg (RS) cells and mononuclear, multinucleate, and lacunar cell variants did not stain with any of the antibodies used. In contrast, lymphohistiocytic RS variants (LϩH cells) reacted positively to BLA.36 and CD79a B-cell markers. Eighteen of 20 affected cats were Ն6 years of age (range, 1-14 years). A sex predilection could not be identified. These findings support the existence of Hodgkin's-like lymphoma in the cat. Proper identification of this disease in the cat will enable further characterization of clinical features and biologic behavior to determine whether there are significant differences in the treatment and prognosis of feline Hodgkin's-like lymphoma compared with non-Hodgkin's lymphoma.

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Hodgkin's Disease

Cited by 10 publications

References 2 publications

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development

Feline Hodgkin's-like Lymphoma: 20 Cases (1992–1999)

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Hodgkin's Disease

Cited by 10 publications

References 2 publications

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development

Feline Hodgkin's-like Lymphoma: 20 Cases (1992–1999)

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⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma