Immune Effects of Bevacizumab: Killing Two Birds with One Stone

Elamin, Yasir Y.; Rafee, Shereen; Toomey, Sinéad; Hennessy, Bryan T.

doi:10.1007/s12307-014-0160-8

Cited by 53 publications

(35 citation statements)

References 64 publications

(80 reference statements)

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“…On the basis of our data, we cannot determine the differential role of the different agents. Certainly for anti-VEGF agents, like bevacizumab, data are available for its potential immune modulatory effect (23,24).…”

Section: Discussionmentioning

confidence: 99%

Induction of Peripheral Effector CD8 T-cell Proliferation by Combination of Paclitaxel, Carboplatin, and Bevacizumab in Non–small Cell Lung Cancer Patients

Goeje

Poncin

Bezemer

et al. 2019

Clinical Cancer Research

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Purpose: Chemotherapy has long been the standard treatment for advanced stage non-small cell lung cancer (NSCLC), but checkpoint inhibitors are now approved for use in several patient groups and combinations. To design optimal combination strategies, a better understanding of the immunemodulatory capacities of conventional treatments is needed. Therefore, we investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on the immune populations associated with the response to checkpoint inhibitors in peripheral blood.Experimental Design: A total of 223 patients with stage IV NSCLC, enrolled in the NVALT12 study, received PCB, with or without nitroglycerin patch. Peripheral blood was collected at baseline and after the first and second treatment cycle, proportions of T cells, B cells, and monocytes were determined by flow cytometry. Furthermore, several subsets of T cells and the expression of Ki67 and coinhibitory receptors on these subsets were determined.Results: Although proliferation of CD4 T cells remained stable following treatment, proliferation of peripheral blood CD8 T cells was significantly increased, particularly in the effector memory and CD45RA þ effector subsets. The proliferating CD8 T cells more highly expressed programmed death receptor (PD)-1 and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) compared with nonproliferating CD8 T cells. Immunologic responders (iR; >2 fold increased proliferation after treatment) did not show an improved progression-free (PFS) or overall survival (OS).Conclusions: Paclitaxel/carboplatin/bevacizumab induces proliferation of CD8 T cells, consisting of effector cells expressing coinhibitory checkpoint molecules. Induction of proliferation was not correlated to clinical outcome in the current clinical setting. Our findings provide a rationale for combining PCB with checkpoint inhibition in lung cancer.

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Section: Discussionmentioning

confidence: 99%

Induction of Peripheral Effector CD8 T-cell Proliferation by Combination of Paclitaxel, Carboplatin, and Bevacizumab in Non–small Cell Lung Cancer Patients

Goeje

Poncin

Bezemer

et al. 2019

Clinical Cancer Research

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“…Bevacizumab is a mAb that inhibits angiogenesis by binding to vascular endothelial growth factor (VEGF), a pro-angiogenesis cytokine. Bevacizumab is not strictly an immunotherapy but may have immunomodulatory effects, such as enhanced T cell recruitment and dendritic cell maturation and migration related to an inhibitory VEGF effect [52] . Bevacizumab is effective in some children with recurrent low-grade glioma [53] and FDA approved for recurrent GBM in adults [54] , but is not immunotherapy in the sense that it does not elicit an anti-tumor immune response.…”

Section: Monoclonal Antibodies and Immunoconjugatesmentioning

confidence: 99%

Immunotherapy for pediatric brain tumors

Landi¹,

Thompson²,

Ashley³

2018

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Immunotherapy, while effective against lymphoid cancers and some solid tumors, has shown less benefit against pediatric brain tumors. Tumor heterogeneity, a suppressive immune microenvironment, and the blood-brain barrier have the potential to diminish any immune-based approach and limit efficacy. More importantly, most pediatric brain tumors are immunologically quiescent, stemming from a low mutational burden. This review focuses on innate vs. adaptive immunotherapeutic approaches and describes how the immunologic context of pediatric brain tumors can help identify well-suited immunotherapies for our patients. In this framework, we will discuss past and current approaches using virotherapy, immunoconjugates, monoclonal antibodies, active immunization, and adoptive cellular therapy, and share our thoughts on how immunotherapy can cure children with brain tumors.

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“…The combination of bevacizumab and avelumab is a rational one based on evidence that endogenous VEGF signalling has a variety of immunomodulatory effects. VEGF-A has been postulated to suppress dendritic cell maturation, increase the presence of immunosuppressive CD34+ haematopoetic progenitor cells in the tumour microenvironment and inhibit T-cell maturation [75]. Another trial combining atezolizumab with bevacizumab (NCT02839707) in a phase II/III setting is randomising platinum resistant patients between 3 arms each containing PLD with either bevacizumab alone (control), atezolizumab alone or bevacizumab and atezolizumab.…”

Section: Checkpoint Blockadementioning

confidence: 99%

Novel Systemic Treatments in High Grade Ovarian Cancer

Samani¹,

Chan²,

Krell³

2018

Ovarian Cancer - From Pathogenesis to Treatment

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Most patients with ovarian cancer present at an advanced stage and are never cured. To improve outcomes a variety of novel systemic strategies are being developed. Traditional cytotoxic chemotherapy is being optimised, anti-angiogenic strategies are already in the clinic and several PARP inhibitors have gained regulatory approval. In addition, immunotherapy is showing promise and novel targeted strategies including against folate receptor alpha are also generating excitement. As our therapeutic choice increases, a challenge will be how to best utilize the options available. Here we discuss recently established and other emerging therapies with a focus on key concepts rather than detailed synopses of trial designs and outcomes.

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Immune Effects of Bevacizumab: Killing Two Birds with One Stone

Cited by 53 publications

References 64 publications

Induction of Peripheral Effector CD8 T-cell Proliferation by Combination of Paclitaxel, Carboplatin, and Bevacizumab in Non–small Cell Lung Cancer Patients

Induction of Peripheral Effector CD8 T-cell Proliferation by Combination of Paclitaxel, Carboplatin, and Bevacizumab in Non–small Cell Lung Cancer Patients

Immunotherapy for pediatric brain tumors

Novel Systemic Treatments in High Grade Ovarian Cancer

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