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Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma.

ABSTRACT: The antibody-drug conjugate (ADC) cAC10-vcMMAE consists of the tubulin inhibitor monomethyl auristatin E (MMAE) conjugated to the chimeric anti-CD30 monoclonal antibody cAC10. This ADC potently interferes with the growth of CD30-positive haematological tumours, including Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma. This study found improved antitumour activity in a preclinical model of HL when SGN-35 was combined with chemotherapeutic regimens such as ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or gemcitabine. Improved efficacy was also observed in high tumour burden models, indicating that combining ADCs with chemotherapeutic agents may be advantageous for the treatment of patients with relapsed or refractory HL.

SUBMITTER: Oflazoglu E

PROVIDER: S-EPMC2440525 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma.

Oflazoglu Ezogelin E Kissler Kim M KM Sievers Eric L EL Grewal Iqbal S IS Gerber Hans-Peter HP

British journal of haematology 20080508 1

The antibody-drug conjugate (ADC) cAC10-vcMMAE consists of the tubulin inhibitor monomethyl auristatin E (MMAE) conjugated to the chimeric anti-CD30 monoclonal antibody cAC10. This ADC potently interferes with the growth of CD30-positive haematological tumours, including Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma. This study found improved antitumour activity in a preclinical model of HL when SGN-35 was combined with chemotherapeutic regimens such as ABVD (doxorubicin, bleomycin, v ...[more]

PMID: 18477046

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Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75.

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| S-EPMC2938259 | biostudies-other

Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma.

Project description:Intravenous brentuximab vedotin (ADCETRIS®) is a targeted antibody-drug conjugate (ADC) active against CD30-positive cancer cells such as those associated with classical Hodgkin lymphoma (HL). In noncomparative, phase 2 trials and in the real-world setting, salvage therapy with brentuximab vedotin resulted in high objective response (complete plus partial remission) rates in patients with relapsed or refractory CD30-positive HL, including as retreatment in patients who had an objective response to previous brentuximab vedotin therapy and subsequently relapsed. These beneficial outcomes were durable during long-term follow-up. As consolidation therapy after autologous haematopoietic stem cell transplant (ASCT) in the multinational, phase 3 AETHERA trial, brentuximab vedotin prolonged progression-free-survival (PFS) compared with placebo at a median follow-up of 30 months (primary analysis), with a 43% reduction in the risk of disease progression or death. The beneficial effects of brentuximab vedotin consolidation therapy were maintained during long-term follow-up. In the clinical trial and real-world setting, brentuximab vedotin had an acceptable tolerability and safety profile, with most adverse events manageable with dose reductions and/or delays [including peripheral sensory neuropathy (PSN) and neutropenia]. With a paucity of treatments available for many patients with relapsed or refractory HL, brentuximab vedotin represents an important option for the management of patients who have failed high-dose chemotherapy/ASCT or at least two prior chemotherapy regimens and as post-ASCT consolidation therapy in patients who are at increased risk/high-risk of relapse or progression after ASCT.

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| S-EPMC7136452 | biostudies-literature

Targeting CD30 Using Brentuximab Vedotin in the Treatment of Hodgkin Lymphoma.

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| S-EPMC7655020 | biostudies-literature

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Project description:Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade. Here, we suggest a novel therapeutic concept based on oncolytic viruses selectively destroying the CD30+-positive cHL tumor cells. Relying on a recently described CD30-specific scFv we have generated CD30-targeted measles virus (MV-CD30) and vesicular stomatitis virus (VSV-CD30). For VSV-CD30 the VSV glycoprotein G reading frame was replaced by those of the CD30-targeted MV glycoproteins. Both viruses were found to be highly selective for CD30-positive cells as demonstrated by infection of co-cultures of target and non-target cells as well as through blocking infection by soluble CD30. Notably, VSV-CD30 yielded much higher titers than MV-CD30 and resulted in a more rapid and efficient killing of cultivated cHL-derived cell lines. Mouse tumor models revealed that intratumorally, as well as systemically injected VSV-CD30, infected cHL xenografts and significantly slowed down tumor growth resulting in a substantially prolonged survival of tumor-bearing mice. Taken together, the data support further preclinical testing of VSV-CD30 as novel therapeutic agent for the treatment of cHL and other CD30+-positive malignancies.

| S-EPMC5849188 | biostudies-literature

Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells.

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| S-EPMC6025985 | biostudies-literature

A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma.

Project description:Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV(+) patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; P(trend) < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV(+) patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike.

| S-EPMC2756127 | biostudies-literature

Brentuximab vedotin for relapsed or refractory CD30+ Hodgkin lymphoma: a multicenter analysis from Asia.

Project description:IntroductionBrentuximab vedotin (SGN-35), an anti-cluster of differentiation (CD)-30 antibody conjugated to the anti-tubulin agent monomethyl auristatin E, has demonstrated promising efficacy and tolerability in relapsed and heavily treated Hodgkin lymphoma (HL). In this study, we report the Asian experience with brentuximab vedotin in patients with relapsed or refractory CD30-positive (CD30+) HL.MethodsThis is an observational, multicenter, retrospective study. Between October 2011 and June 2013, a total of 22 patients were treated with brentuximab vedotin under a named patient program in Asia. Patients received a 30 min infusion of brentuximab vedotin at a dose of 1.8 mg/kg of body weight every 3 weeks.ResultsFour patients (18.2%) showed a complete response, and the overall response rate was 72.7%. The median duration of response was 4.4 months (range 1.0-17.4). The median progression-free survival was 5.7 months, and the median overall survival has not yet been reached. The 1-year expected survival rate was 67.2%. The most common grade 3/4 adverse events were neutropenia (n=7; 31.8%). No patients experienced grade 3/4 sensory neuropathy.ConclusionsThese results confirm that brentuximab vedotin as a single agent is also effective and well tolerated when used in Asian patients with relapsed and refractory CD30+ HL.

| S-EPMC4196794 | biostudies-literature

Advances in CD30- and PD-1-targeted therapies for relapsed or refractory Hodgkin lymphoma.

Project description:The current standard approach for relapsed or refractory (R/R) Hodgkin lymphoma (HL) is salvage chemotherapy, followed by autologous stem cell transplantation (ASCT). However, this therapeutic regimen is successful in only half of patients with relapsed or refractory classical HL. In addition, some patients with R/R HL are ineligible for ASCT. To improve survival time and quality of life and decrease the acute and long-term toxicities of therapy, many schemes for the treatment of R/R HL have emerged. Recently, the use of targeted therapy and immunotherapy represents an important advance in the treatment of R/R HL. The CD30 antibody drug conjugate brentuximab vedotin (BV) and programmed death-1 (PD-1) receptor checkpoint inhibitors nivolumab and pembrolizumab are effective and well-tolerated treatments for R/R HL patients, broadening treatment options for these patients. BV and anti-PD-1 antibodies can be used as monotherapy or combined with other chemotherapy regimens for rescue treatment, consolidation treatment and second-line treatment of R/R HL. In this article, we review current pathobiology knowledge of R/R HL and summarize recent advances in therapy schemes.

| S-EPMC8661193 | biostudies-literature

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