New antibody drug treatments for lymphoma

Mayes, Sam; Brown, N N; Illidge, Tim

doi:10.1517/14712598.2011.560569

Cited by 17 publications

(14 citation statements)

References 128 publications

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“…Since the initial approval of rituximab in 1997, the continued success of monoclonal antibody (mAb) therapy in treating various types of lymphoma and leukemia has spurred considerable development of novel therapeutics, including both naked antibody approaches and antibodydrug conjugates (1,2). This success is thought to be driven, in part, by the accessibility of these types of tumors to antibodies and immune effector cells, as well as the number of tissue-specific receptors that provide potential therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Development of a Human Monoclonal Antibody for Potential Therapy of CD27-Expressing Lymphoma and Leukemia

Vitale

Thomas

et al. 2012

Clinical Cancer Research

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Purpose: The TNF receptor superfamily member CD27 is best known for its important role in T-cell immunity but is also recognized as a cell-surface marker on a number of B-and T-cell malignancies. In this article, we describe a novel human monoclonal antibody (mAb) specific for CD27 with properties that suggest a potential utility against malignancies that express CD27.Experimental Design: The fully human mAb 1F5 was generated using human Ig transgenic mice and characterized by analytical and functional assays in vitro. Severe combined immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells were administered 1F5 to investigate direct antitumor effects. A pilot study of 1F5 was conducted in non-human primates to assess toxicity.Results: 1F5 binds with high affinity and specificity to human and macaque CD27 and competes with ligand binding. 1F5 activates T cells only in combination with T-cell receptor stimulation and does not induce proliferation of primary CD27-expressing tumor cells. 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi tumors, which may be mediated through direct effector mechanisms such as antibody-dependent cellular cytotoxicity. Importantly, administration of up to 10 mg/kg of 1F5 to cynomolgus monkeys was well tolerated without evidence of significant toxicity or depletion of circulating lymphocytes.Conclusions: Collectively, the data suggest that the human mAb 1F5, which has recently entered clinical development under the name CDX-1127, may provide direct antitumor activity against CD27-expressing lymphoma or leukemia, independent of its potential to enhance immunity through its agonistic properties.

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Section: Introductionmentioning

confidence: 99%

Development of a Human Monoclonal Antibody for Potential Therapy of CD27-Expressing Lymphoma and Leukemia

Vitale

Thomas

et al. 2012

Clinical Cancer Research

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“…49 The patient first receives tositumomab, followed by the infusion of tositumomab radiolabelled with iodine-131. This is the same antibody covalently bound to the radionuclide iodine-131.…”

Section: Numerous Clinical Trials Have Utilised a Wide Range Of Bio-vmentioning

confidence: 99%

Application of Radionuclides and Antibody-Drug Conjugates to Target Cancer

Kitson¹

2014

Cancer Stud Mol Med Open J

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Radionuclide therapy and antibody-drug conjugates are used to locate and kill cancer cells by the utilisation of monoclonal antibodies. These bio-vectors are able to transport a cytotoxic drug payload and/or radiation in the form of alpha or beta particles to bind onto antigen specific cancer cells initiating apoptosis. This inaugural article aims to deliver a brief account of these targeted therapies in the treatment of oncological disease states such as leukaemia, non-Hodgkin's lymphoma, neuroendocrine tumours, breast cancer and prostate cancer bone metastases.

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“…RIT is a systemic treatment that has shown promising clinical remission rates in metastatic cancers such as non-Hodgkin lymphoma (NHL) and MM (Chatterjee et al, 2006;Mayes et al, 2011). Several monoclonal antibodies (MAbs) targeting the myeloma cell or the bone marrow microenvironment have been tested in preclinical and clinical studies (van de Donk et al, 2011); these MAbs are potentially amenable to RIT.…”

Section: Radioimmunotherapy (Rit)mentioning

confidence: 99%