Cocktails for cancer with a measure of immunotherapy

Ledford, Heidi

doi:10.1038/532162a

Cited by 57 publications

(40 citation statements)

References 6 publications

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“…Fusi and Dalgleish emphasized that there must be a place for back‐to‐basic, simpler approaches, which just might prime the tumour environment to respond better to checkpoint inhibitors, increase the therapeutic index and convert non‐responders into responders . In fact, spectacular therapeutic improvement in childhood cancer was achieved through ‘a reassessment of the tools in hand’, applying them as combination therapies . A combination therapy consisting of basic low‐tech approaches and immune checkpoint drugs in off‐label low doses seems to be safer and more efficient in advanced cancer patients than the currently used approved protocols.…”

Section: Proof‐of‐principle Of Low‐dose Ici Therapy Has Been Demonstrmentioning

confidence: 99%

“…77 In fact, spectacular therapeutic improvement in childhood cancer was achieved through 'a reassessment of the tools in hand', applying them as combination therapies. 78 A combination therapy consisting of basic low-tech approaches and immune checkpoint drugs in off-label low doses seems to be safer and more efficient in advanced cancer patients than the currently used approved protocols.…”

Section: Low-dose Ici Therapy Has Been Demonstrated In 111 Single Casmentioning

confidence: 99%

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Exploiting autoimmunity unleashed by low‐dose immune checkpoint blockade to treat advanced cancer

Bakács¹,

Moss²,

Kleef³

et al. 2019

Scand J Immunol

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As a result of the cancer immunotherapy revolution, more than 2000 immuno‐oncology agents are currently being tested or are in use to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by the blockade of co‐inhibitory signals. Unfortunately, manipulation of the co‐inhibitory receptors has also resulted in a safety issue: widespread iatrogenic immune‐related adverse events (irAEs). Autoimmunity is emerging as the nemesis of immunotherapy. Originally, it was assumed that CTLA‐4 blockade selectively targets T cells relevant to the antitumour immune response. However, an uncontrolled pan T cell activation was induced compromising tolerance to healthy self‐tissues. The irAEs are very similar to that of a chronic graft‐versus‐host‐disease (GVHD) reaction following allogeneic bone marrow transplantation (BMT). We hypothesized that ipilimumab induced a graft‐versus‐malignancy (GVM) effect, which eradicated metastatic melanoma in a minority of patients, but also involved an auto‐GVHD reaction that resulted in widespread autoimmunity in the majority. Therefore, we argued for a profound theoretical point against the consensus of experts. The task is not to desperately put the genie back in the bottle by immune‐suppressive treatments, but instead to harness the autoimmune forces. In this way, the same goal could be achieved by an antibody as by the adoptive transfer of alloreactive donor lymphocytes, but without severe GVHD. The proof‐of‐principle of a low‐dose‐combination immune checkpoint therapy, consisting only of approved drugs and treatments, was demonstrated in 111 stage IV cancer patients.

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Section: Proof‐of‐principle Of Low‐dose Ici Therapy Has Been Demonstrmentioning

confidence: 99%

Section: Low-dose Ici Therapy Has Been Demonstrated In 111 Single Casmentioning

confidence: 99%

Exploiting autoimmunity unleashed by low‐dose immune checkpoint blockade to treat advanced cancer

Bakács¹,

Moss²,

Kleef³

et al. 2019

Scand J Immunol

View full text Add to dashboard Cite

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“…The use of these immune checkpoint inhibitors (ICIs) institutes a new therapy for gastrointestinal (GI) malignancies after the recent FDA approvals of PD‐1 inhibitors for microsatellite instable (MSI) tumors. Since the first ICIs were approved, clinical research also evaluates other targets within the “cancer immunity cycle” and investigating ICIs in combination with numerous other established or novel drugs . The first clinical evidence of phase II trials and phase I expansion cohorts at the end of 2017 is available for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Since the first ICIs were approved, clinical research also evaluates other targets within the "cancer immunity cycle" and investigating ICIs in combination with numerous other established or novel drugs. 115,117,118 The first clinical evidence of phase II trials and phase I expansion cohorts at the end of 2017 is available for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab.…”

Section: Immuno-oncology In Ecs: New Promising Strategies and Therapementioning

confidence: 99%

Molecular landscape of esophageal cancer: implications for early detection and personalized therapy

Talukdar

Pietro

Secrier

et al. 2018

Annals of the New York Academy of Sciences

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Esophageal cancer (EC) is one of the most lethal cancers and a public health concern worldwide, owing to late diagnosis and lack of efficient treatment. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are main histopathological subtypes of EC that show striking differences in geographical distribution, possibly due to differences in exposure to risk factors and lifestyles. ESCC and EAC are distinct diseases in terms of cell of origin, epidemiology, and molecular architecture of tumor cells. Past efforts aimed at translating potential molecular candidates into clinical practice proved to be challenging, underscoring the need for identifying novel candidates for early diagnosis and therapy of EC. Several major international efforts have brought about important advances in identifying molecular landscapes of ESCC and EAC toward understanding molecular mechanisms and critical molecular events driving the progression and pathological features of the disease. In our review, we summarize recent advances in the areas of genomics and epigenomics of ESCC and EAC, their mutational signatures and immunotherapy. We also discuss implications of recent advances in characterizing the genome and epigenome of EC for the discovery of diagnostic/prognostic biomarkers and development of new targets for personalized treatment and prevention.

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“…There is an explosion of clinical trials to test combinations of anticancer therapies having different cellular targets: about 40 clinical trials were planned in 2015 with combination therapy versus about 10 for single-drug therapy [1]. Of interest, the use of already FDA-approved drugs is less time consuming and decreases the overall costs of combination therapy research [2].…”

Section: Introductionmentioning

confidence: 99%

First-in-Class Combination Therapy of a Copper(II) Metallo-Phosphorus Dendrimer with Cytotoxic Agents

et al. 2018

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The metallo-phosphorus dendrimer 1G3-Cu (generation 3 dendrimer bearing 48 conjugated copper(II) on its surface) has antiproliferative activity related to its capacity to activate Bax translocation. In the present study, we evaluate the activity of an association of 1G3-Cu with 5 cytotoxic agents used in chemotherapy having different modes of action. Data show no additive effect with camptothecin and cisplatin, additivity with paclitaxel and MG132, and synergy with doxorubicin. Results suggest that the multivalent Cu-conjugated dendrimer 1G3-Cu (activator of Bax translocation) plays an important role in boosting the clinical impact of Bax accumulation stimulated by the proteasome inhibitor MG132, antimitotic taxanes, and the topo II inhibitor doxorubicin.

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Cocktails for cancer with a measure of immunotherapy

Cited by 57 publications

References 6 publications

Exploiting autoimmunity unleashed by low‐dose immune checkpoint blockade to treat advanced cancer

Exploiting autoimmunity unleashed by low‐dose immune checkpoint blockade to treat advanced cancer

Molecular landscape of esophageal cancer: implications for early detection and personalized therapy

First-in-Class Combination Therapy of a Copper(II) Metallo-Phosphorus Dendrimer with Cytotoxic Agents

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