Anti-CD20 Directed Therapy of B Cell Lymphomas: Are New Agents Really Better?

Freeman, Ciara L.; Sehn, Laurie H.

doi:10.1007/s11912-018-0748-0

Cited by 13 publications

(14 citation statements)

References 97 publications

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“…Anti-CD20 antibody therapies are one example. Non-Hodgkin lymphoma (NHL) affects 70,000 adults each year in the USA and several anti-CD20 antibodies are available or in development for CD20-positive disease (86,87). However, in the USA only 400 children are diagnosed annually with CD20-positive NHL across more than 200 pediatric oncology centers; fewer than 80 relapse, and even fewer relapse a second time and would be eligible for clinical trials for refractory mature B-cell NHL, which means that pediatric trials of novel CD20 antibodies are limited to a small number of eligible patients treated in a large number of centers (8).…”

Section: Science and Drug Development For Allmentioning

confidence: 99%

Science and health for all children with cancer

Lam

Howard

Bouffet

et al. 2019

Science

265

190

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Each year ~429,000 children and adolescents aged 0 to 19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in high-income countries (HICs) but are less than 30% for the 384,000 children in lower-middle-income countries (LMICs). Improved survival rates in HICs have been achieved through multidisciplinary care and research, with treatment regimens using mostly generic medicines and optimized risk stratification. Children’s outcomes in LMICs can be improved through global collaborative partnerships that help local leaders adapt effective treatments to local resources and clinical needs, as well as address common problems such as delayed diagnosis and treatment abandonment. Together, these approaches may bring within reach the global survival target recently set by the World Health Organization: 60% survival for all children with cancer by 2030.

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Section: Science and Drug Development For Allmentioning

confidence: 99%

Science and health for all children with cancer

Lam

Howard

Bouffet

et al. 2019

Science

265

190

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“…This work is indeed at the stage where it can transition into clinical models. For example, how effective such cathepsin therapeutics maybe in a combined therapeutic setting (such as with Tocilizumab [93] or Rituximab [94]), is yet another important application of the above research and the outcomes for which are eagerly awaited. The observations that Tocilizumab or Rituximab also dampen signaling transduction pathways which otherwise activate intracellular cathepsin production (for example IFN- and IL-6 signaling [95,96]), could also be an important consideration.…”

Section: Clinical Implications and Applicationsmentioning

confidence: 99%

Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer

et al. 2019

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In keeping with recent developments in basic research; the importance of the Cathepsins as targets in cancer therapy have taken on increasing importance and given rise to a number of key areas of interest in the clinical setting. In keeping with driving basic research in this area in a translational direction; recent findings have given rise to a number of exciting developments in the areas of cancer diagnosis; prognosis and therapeutic development. As a fast-moving area of research; the focus of this review brings together the latest findings and highlights the translational significance of these developments.

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“…It has been used alongside multiple drug CHOP chemotherapy (R-CHOP) in the treatment of B cell type lymphoid tumors, including non-Hodgkin B cell lymphoma, with dramatic success 6 , 7 . Following the success of R-CHOP therapy, several kinds of CD20 antibody drugs were developed to obtain a more potent cytopathic effect on B cell lymphoma cells, and among them, ofatumumab and obinutuzumab were recently launched 8 . Obinutuzumab, in particular, is a glycoengineered CD20 antibody with reduced fucose modification of the heavy chain constant region 9 .…”

Section: Introductionmentioning

confidence: 99%

“…drugs were developed to obtain a more potent cytopathic effect on B cell lymphoma cells, and among them, ofatumumab and obinutuzumab were recently launched 8 . Obinutuzumab, in particular, is a glycoengineered CD20 antibody with reduced fucose modification of the heavy chain constant region 9 .…”

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confidence: 99%

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Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment

Mizuno

Kato

Kaneko

et al. 2020

Sci Rep

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Lymphoma is the most common hematological cancer in dogs. Canine diffuse large B cell lymphoma shows a relatively good response to treatment with multi-agent cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, the 2-year survival rate is as low as 20%. For human B cell type lymphoma, the anti-CD20 chimeric antibody, rituximab, was developed two decades ago. The combination of rituximab and CHOP chemotherapy was highly successful in improving patient prognosis. However, no anti-canine CD20 antibody is available for the treatment of canine lymphoma. During this study, a rat anti-canine CD20 monoclonal antibody was established. We also generated a rat-canine chimeric antibody against canine CD20 designed for clinical application. This chimeric antibody (4E1-7-B) showed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the canine B cell lymphoma cell line CLBL-1. Moreover, to obtain stronger ADCC activity, a defucosylated 4E1-7-B antibody (4E1-7-B_f) was also generated, and it showed tenfold stronger ADCC activity compared with 4E1-7-B. 4E1-7-B_f as well as 4E1-7-B suppressed the growth of CLBL-1 tumors in an immunodeficient xenotransplant mouse model. Finally, a single administration of 4E1-7-B_f induced considerable peripheral B cell depletion in healthy beagles. Thus, 4E1-7-B_f is a good antibody drug candidate for canine B cell type lymphoma. Lymphoma is one of the most common hematological cancers in dogs, and is important as a point of comparison for human lymphoma 1. Canine lymphomas are classified into T cell and B cell types according to their cell of origin. B cell lymphoma, the most common type which is similar to human diffused large B cell lymphoma (DLBCL), has a favorable prognosis compared to T cell lymphoma because the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen of chemotherapy leads to remission in most cases. However, the 2-year survival rate is only 20%, and most cases recur after remission, finally proving refractory to chemotherapy 2. Therefore, a novel therapy is required. Recently, several novel treatment strategies for canine lymphoma, including low molecular weight inhibitors, have been established 3 , leading to the expectation of an improved prognosis for dogs with lymphoma. Nevertheless, antibody treatment for canine lymphoma has not yet been established. Among antibody therapies for cancer, rituximab, an anti-human CD20 antibody, is the oldest and most widely distributed. Rituximab is a chimeric antibody in which the constant region of the original anti-human CD20 mouse antibody was replaced with a human constant region 4. Rituximab binds to human CD20 molecules and directly induces apoptotic cell death in addition to its function through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) 5. It has been used alongside multiple drug CHOP chemotherapy (R-CHOP) in the treatment of B cell type lymphoid tumors, includin...

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Anti-CD20 Directed Therapy of B Cell Lymphomas: Are New Agents Really Better?

Cited by 13 publications

References 97 publications

Science and health for all children with cancer

Science and health for all children with cancer

Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer

Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment

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