Atezolizumab in combination with bevacizumab enhances migration of antigen-specific T-cells in metastatic renal cell carcinoma

Wallin, JJ; Bendell, J. C.; Funke, R; Sznol, M; Korski, K; Jones, S; Hernandez, G; Mier, J; He, X; Hodi, FS; Denker, M; Leveque, V; Cañamero, M; Babitski, G; Koeppen, H; Aiai, J; Sharma, N; Gaire, F; Ds, Chen; Waterkamp, D; Hegde, P.; McDermott, DF

doi:10.21417/b78g65

Cited by 11 publications

(11 citation statements)

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“…Furthermore, a separate study of patients with RCC investigating the effect that bevacizumab plus atezolizumab had versus bevacizumab alone found that the combination therapy demonstrated a reduction in neovasulature-related gene expression and decreased microvascular density. The treatment was also associated with an increased tumour infiltration of CD8+ T cells as demonstrated by immunohistochemical staining of cells [83]. This study also demonstrated that MHC Class I is upregulated as a result of the treatment and that both intratumoural CD8+ T cells and macrophages increased as well.…”

Section: Synergy Of Anti-angiogenic Agents With Immunomodulatory Therapysupporting

confidence: 64%

Angiogenesis and Its Role in the Tumour Microenvironment: A Target for Cancer Therapy

Frentzas¹,

Lum²,

Chen³

2020

Current Cancer Treatment

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The process of angiogenesis refers to the growth of new blood vessels from existing ones. Tumours can produce factors in the micro-environment which act on blood vessels to promote angiogenesis. It is therefore considered to be fundamental in tumour progression and metastatic dissemination. This neovascularization can be regulated by numerous endogenous factors in the tumour micro-environment. As a result, anti-angiogenic therapies have been developed in the hope of targeting this process to reduce tumour growth and progression. However, only a proportion of patients respond to therapy, indicating the presence of treatment resistance in some. In this chapter, we aim to highlight the process of angiogenesis and to review pivotal evidence for the use of anti-angiogenic therapies thus far (alone and in combination with other agents). Finally, we will illustrate recent evidence for the discovery of biomarkers for anti-angiogenic therapies and potential mechanisms of resistance to such agents.

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Section: Synergy Of Anti-angiogenic Agents With Immunomodulatory Therapysupporting

confidence: 64%

Angiogenesis and Its Role in the Tumour Microenvironment: A Target for Cancer Therapy

Frentzas¹,

Lum²,

Chen³

2020

Current Cancer Treatment

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“…Another line of experimental evidence shows that VEGF-A suppresses antitumor immunity by affecting other immune cells. Indeed, in association with immune checkpoint blockade, targeting of VEGF-A improves NK cell responses to chemotherapy and improves T-cell-mediated antitumor immunity [ 53 , 54 ]. We found that in colorectal tumors, recombinant anti-OLFML3 antibody treatment decreases the abundance of mature macrophages and TAMs while increasing the recruitment of NK-like T cells.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of anti-OLFML3 and anti-PD-1 antibodies increases tumor infiltration by inflammatory myeloid cells, B cells, T lymphocytes, and NKT cells, and inhibits tumor growth more effectively than either agent used alone. Such combinations of angiogenesis-targeting agents and checkpoint inhibitors have been recommended for the treatment of the poorly immunogenic CMS4 CRC subtype [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Future studies are needed to determine how to best exploit the therapeutic potential of combined OLFML3 inhibition and treatment with immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Targeting OLFML3 in Colorectal Cancer Suppresses Tumor Growth and Angiogenesis, and Increases the Efficacy of Anti-PD1 Based Immunotherapy

Stalin

Imhof

Coquoz

et al. 2021

Cancers

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The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC.

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“…Additionally, Wallin et al 33 detailed, in a cohort of 10 subjects with metastatic renal cell carcinoma treated on GP28328, that combination atezolizumab and bevacizumab resulted in increased intratumoral CD8 + T-cells, with a related increase in intratumoral MHC-1, natural killer cells, type 1 helper T-cells, T-effector markers and chemokines (CX3Cl1; fractalkine). These synergistic effects are hypothesized to stem from the proinflammatory impact of vascular endothelial growth factor (VEGF) blockade, as well as hypoxia in the tumor microenvironment.…”

Section: On Gog 229-e Received Prior Radiation Therapy)mentioning

confidence: 99%

Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: review of current phase III immunotherapy clinical trials

Eskander

Powell

2021

Ther Adv Med Oncol

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The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer.

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Atezolizumab in combination with bevacizumab enhances migration of antigen-specific T-cells in metastatic renal cell carcinoma

Cited by 11 publications

References 0 publications

Angiogenesis and Its Role in the Tumour Microenvironment: A Target for Cancer Therapy

Angiogenesis and Its Role in the Tumour Microenvironment: A Target for Cancer Therapy

Targeting OLFML3 in Colorectal Cancer Suppresses Tumor Growth and Angiogenesis, and Increases the Efficacy of Anti-PD1 Based Immunotherapy

Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: review of current phase III immunotherapy clinical trials

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