Featured
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News & Views |
When an embarrassment of riches isn’t enough
Data on a new treatment approach utilizing bispecific monoclonal antibodies targetting B-cell maturation antigen (BCMA) were recently published, yielding very encouraging results in the setting of relapsed and/or refractory multiple myeloma (RRMM). How to safely and effectively deliver this treatment to patients and where it fits in the RRMM treatment paradigm are important questions for the future.
- Krina Patel
- & Sagar Lonial
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Review Article |
COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety
Vaccination against COVID-19 confers robust protection from severe disease. However, the extent to which this applies to patients with cancer remains uncertain given that these patients were excluded from most of the pivotal studies. In this Review, the authors provide an overview of the efficacy and immunogenicity of COVID-19 vaccines in patients with cancer, and discuss alternatives to vaccination for those who might be unable to develop a proficient immune response following vaccination.
- Annika Fendler
- , Elisabeth G. E. de Vries
- & Marie von Lilienfeld-Toal
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News & Views |
The NKG2A immune checkpoint — a new direction in cancer immunotherapy
Inhibition of the NKG2A immune checkpoint restores natural killer cell and T cell effector function in preclinical cancer models. In addition, NKG2A blockade in combination with other therapeutic antibodies is showing encouraging responses in a subset of patients with metastatic colorectal or head and neck cancer. However, established biomarkers of response are lacking, and larger trials are needed to enable firm conclusions to be drawn about whether NKG2A inhibition complements existing immunotherapies.
- Benjamin C. Creelan
- & Scott J. Antonia
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Perspective |
Time to abandon single-site irradiation for inducing abscopal effects
Many clinical trials are testing the safety and/or efficacy of combining radiotherapy with immunotherapy, nearly all using a single-site irradiation (or ‘abscopal’) approach, but emerging evidence suggests that this approach likely produces suboptimal results. The authors of this Perspective provide a biological rationale supporting the abandonment of the abscopal approach, and instead advocate exploring comprehensive irradiation of multiple/all lesions.
- Eric D. Brooks
- & Joe Y. Chang
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Review Article |
Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa
The combination of immunotherapies with other therapeutic modalities, including anti-angiogenic agents, is currently under investigation to improve the outcomes of patients receiving immunotherapies. In this article, the authors review the effects mediated by anti-angiogenic agents that might increase the efficacy of immunotherapies and discuss the possibility that immunotherapies might increase the efficacy of anti-angiogenic agents and/or promote changes in the tumour vasculature.
- Kabir A. Khan
- & Robert S. Kerbel
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Comment |
Approvals in 2017: gene therapies and site-agnostic indications
In 2017, FDA Oncology approved 17 new drug and biologic applications, 32 supplemental drug and biologic applications, and two biosimilar applications in oncology. These actions included landmark approvals of two chimeric antigen receptor T cell therapies and the first site-agnostic, biomarker-defined approval. Three next-generation sequencing 'oncopanels' designed to detect hundreds of somatic genetic aberrations were also approved.
- Gideon M. Blumenthal
- & Richard Pazdur
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Year in Review |
Changes in expectations for metastatic urothelial carcinoma
2017 saw the publication of clinical trial data and the approval of new treatment approaches for metastatic urothelial carcinoma. Pembrolizumab is now a well-established treatment for patients with disease progression after cisplatin, with high-level evidence supporting its superiority over second-line chemotherapy. For patients ineligible for cisplatin, atezolizumab and pembrolizumab provide meaningful clinical benefit as frontline therapies.
- Joaquim Bellmunt
- & Rosa Nadal
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Review Article |
Chimeric antigen receptor T-cell therapies for lymphoma
Cell-based immunotherapies are showing great promise in the treatment of even the most treatment-refractory of haematological malignancies. Herein, Jennifer Brudno and James Kochenderfer review the results obtained to date with CAR-T-cell therapies for lymphoma. They also discuss what has been learned regarding the limitations of CAR-T-cell therapies and areas for improvement relating to toxicity management, the design of CAR-T-cell products, conditioning regimens, and combination therapies.
- Jennifer N. Brudno
- & James N. Kochenderfer
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News & Views |
T-DM1 — an important agent in the history of breast cancer management
Updated results from the EMILIA and TH3RESA trials in patients with advanced-stage HER2-positive breast cancer confirm the overall survival benefit and favourable safety profile of T-DM1 after prolonged follow-up durations. The efficacy of T-DM1 as a second or later line of treatment indicates that HER2 is a relevant therapeutic target throughout the course of the disease.
- Otto Metzger-Filho
- & Eric P. Winer
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Review Article |
Antibody–drug conjugates in glioblastoma therapy: the right drugs to the right cells
Few therapeutic options are currently available for patients with glioblastoma, which are associated with a poor prognosis. Therapies with monoclonal antibodies, alone or linked to cytotoxic payloads, are currently being explored in these patients. Herein, the authors summarize therapeutic strategies based on antibody–drug conjugates (ADCs), targeted against EGFR, and discuss key aspects such as the blood–brain barrier, resistance mechanisms, and the development of specific biomarkers.
- Hui K. Gan
- , Martin van den Bent
- & Andrew M. Scott
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Review Article |
Immunological off-target effects of imatinib
Growing evidence indicates that anticancer agents can mobilize the immune system against the tumour. By reinstating immunosurveillance, the activity of conventional and targeted therapies might be prolonged beyond cessation of the treatment. The authors of this Review, explore how imatinib likely operates through immune and cell-autonomous mechanisms, which has practical implications for defining biomarkers that predict response or resistance to imatinib, as well as for the design of novel combination treatments.
- Laurence Zitvogel
- , Sylvie Rusakiewicz
- & Guido Kroemer
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Review Article |
Driving CAR T-cells forward
Clinical trials of CAR-T-cell therapy for patients with B-cell malignancies have yielded impressive results. Ongoing clinical trials are now testing CAR-T-cell therapies with new designs for the treatment of other haematological and solid malignancies. The authors of this Review present an overview of the approaches that are currently being tested in registered clinical trials, and discuss strategies that can increase the antitumour efficacy and safety of CAR-T-cell therapy.
- Hollie J. Jackson
- , Sarwish Rafiq
- & Renier J. Brentjens
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Review Article |
The future of cancer treatment: immunomodulation, CARs and combination immunotherapy
The aim of immunotherapy is to treat cancer by enabling the immune system to attack the tumour. In the past decade, remarkable results have been obtained in clinical trials with immunotherapy for patients with advanced-stage cancer. Two types of immunotherapy have been used in the majority of trials conducted in the past decade: immune cell-targeted antibody therapy and adoptive cellular therapy. Herein, the latest advances in both modalities are discussed, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended.
- Danny N. Khalil
- , Eric L. Smith
- & Jedd D. Wolchok
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