Clinical and immunological responses after CD30-specific chimeric antigen receptor–redirected lymphocytes

Ramos, Carlos A.; Ballard, Brandon; Zhang, Huimin; Dakhova, Olga; Gee, Adrian P.; Mei, Zhuyong; Bilgi, Mrinalini; Wu, Meng; Líu, Hao; Grilley, Bambi; Bollard, Catherine M.; Chang, Bill H.; Rooney, Cliona M.; Brenner, Malcolm K.; Heslop, Helen E.; Dotti, Gianpietro; Savoldo, Barbara

doi:10.1172/jci94306

Cited by 317 publications

(265 citation statements)

References 41 publications

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“…The reported results in 2 patients with ALCL(120) showed 1 CR that persisted 9 months after the fourth infusion of CD30 CAR-Ts. Although CD30 may also be expressed by normal activated T cells, no patients developed impaired virus-specific immunity.…”

Section: Immunotherapeutic Strategies For T Cell Leukemia and Lymphomamentioning

confidence: 91%

Novel Immunotherapies for T Cell Lymphoma and Leukemia

Ghione

Moskowitz

Paola

et al. 2018

Curr Hematol Malig Rep

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Purpose of review: novel immunotherapies such as checkpoint inhibitors, bispecific and chimeric antigen receptor T cells are leading to promising responses when treating solid tumors and hematological malignancies. T cell neoplasms include leukemia and lymphomas that are derived from T cells. These are rare diseases with generally poor clinical outcomes. This review describes the rational and preliminary results of these approaches for people with T cell lymphoma and leukemia. Recent findings: for T cell neoplasms, despite significant research effort, only few agents, such as monoclonal antibodies and allogeneic stem cell transplantation, showed some clinical activity. One of the major hurdles to targeting T cell neoplasms is that activation or elimination of T cells, either normal or neoplastic, can cause significant toxicity. A need to develop novel safe and effective immunotherapies for T cell neoplasms exists. Summary: In this review, we will discuss the rationale for immunotherapy of T cell leukemia and lymphoma and present the most recent therapeutic approaches.

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Section: Immunotherapeutic Strategies For T Cell Leukemia and Lymphomamentioning

confidence: 91%

Novel Immunotherapies for T Cell Lymphoma and Leukemia

Ghione

Moskowitz

Paola

et al. 2018

Curr Hematol Malig Rep

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“…Analysis of biopsied tissues by real time quantitative polymerase chain reaction and immunohistochemistry revealed the trafficking of CAR‐T cells into the targeted sites and reduction of the expression of CD30 in tumours (Wang et al , ). In another phase I dose escalation study, 9 patients with R/R HL or ALCL were infused with autologous T cells expressing the CD30‐specific CAR encoding the CD28 costimulatory endodomain (Ramos et al , ). Of 7 patients with relapsed HL, 2 entered CR lasting more than 2 years, and 3 had transient SD.…”

Section: Adaptive Immunotherapiesmentioning

confidence: 99%

Novel therapeutic agents for relapsed classical Hodgkin lymphoma

Keudell

Younes

2018

Br J Haematol

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Summary Hodgkin Lymphoma (HL) is a B‐cell lymphoproliferative disorder with an excellent prognosis for the majority of patients who are treated with multi‐agent chemotherapy, with or without radiation. A subset of patient, however, does not respond to therapy or relapses after accomplishing an initial response. Their outcome is poor and new treatment strategies are urgently needed for this patient population. Recent advances in the understanding of the tumour biology of HL and its microenvironment have ushered a new era of targeted‐ and immuno‐therapies with remarkable activity. Most notably, the antibody‐drug conjugate brentuximab‐vedotin, and the immune checkpoint blockers pembrolizumab and nivolumab have recently been approved by the US Food and Drug Administration and have transformed the therapeutic landscape of this disease. Other novel drug compounds are being investigated either as single agents or in combination and hold promise to further the field.

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“…Although the vast majority of CAR-T-cell trials for hematologic diseases have focused on CD19redirected T cells, there are a number of new trials targeting other B-cell antigens (including CD20, CD22, CD30, and B-cell maturation antigen [109][110][111][112], T-cell antigens, as well as early trials targeting antigens associated with acute myeloid leukemia. [113][114][115][116][117][118][119][120][121][122][123][124] The elements of success with CAR-T therapies As with HCT, CAR-T-cell therapies are composed of multiple stages, and at each stage, critical elements exist that contribute to success or failure. It is useful to divide CAR-T cellular therapies into 4 distinct stages: (1) patient selection and cell manufacturing;…”

Section: Car-t Cells: New Efficacy New Toxicitiesmentioning

confidence: 99%

Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis

Kean

2018

Blood

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Cellular therapies play a major and expanding role in the treatment of hematologic diseases. For each of these therapies, a narrow therapeutic window exists, where efficacy is maximized and toxicities minimized. This review focuses on one of the most established cellular therapies, hematopoietic stem cell transplant, and one of the newest cellular therapies, chimeric antigen receptor-T cells. In this review, I will discuss the current state of the field for clinical end point analysis with each of these therapeutics, including their critical toxicities, and focus on the major elements of success for each of these complex treatments for hematologic disease.

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Clinical and immunological responses after CD30-specific chimeric antigen receptor–redirected lymphocytes

Cited by 317 publications

References 41 publications

Novel Immunotherapies for T Cell Lymphoma and Leukemia

Novel Immunotherapies for T Cell Lymphoma and Leukemia

Novel therapeutic agents for relapsed classical Hodgkin lymphoma

Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis

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