Targeting immune effector cells to promote antibody-induced cytotoxicity in cancer immunotherapy

Houot, Roch; Kohrt, Holbrook E.; Marabelle, Aurélien; Levy, Ronald

doi:10.1016/j.it.2011.07.003

Cited by 55 publications

(48 citation statements)

References 69 publications

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“…94,95 Overall, these results show that besides their targeted activities, ADCP can help antibody-based therapies to achieve the desirable 'off-target' induction of antitumour immunity (Figure 2). 93 This raises similar precedence for other immunotherapies targeted towards the cancer cells, that is, anti-PD-L1 antibodies. This is further supported by recent observations of FcγRs modulating the activity of the PD-1/PD-L1 axis.…”

Section: Regulated Necrosismentioning

confidence: 78%

“…92 Some clinical observations suggest a correlation between FcγRIIIa (CD16) or FcγRIIa (CD32) polymorphisms and a response to rituximab, trastuzumab and cetuximab. 93 Moreover, few of these therapies can liberate co-stimulatory signals from cancer cells (required to make ADCP immunogenic), for example, rituximab causing release of the TLR agonist, HMGB1. 94,95 Overall, these results show that besides their targeted activities, ADCP can help antibody-based therapies to achieve the desirable 'off-target' induction of antitumour immunity (Figure 2).…”

Section: Regulated Necrosismentioning

confidence: 99%

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Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

et al. 2016

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Phagocytosis of dying cells is a major homeostatic process that represents the final stage of cell death in a tissue context. Under basal conditions, in a diseased tissue (such as cancer) or after treatment with cytotoxic therapies (such as anticancer therapies), phagocytosis has a major role in avoiding toxic accumulation of cellular corpses. Recognition and phagocytosis of dying cancer cells dictate the eventual immunological consequences (i.e., tolerogenic, inflammatory or immunogenic) depending on a series of factors, including the type of 'eat me' signals. Homeostatic clearance of dying cancer cells (i.e., tolerogenic phagocytosis) tends to facilitate pro-tumorigenic processes and actively suppress antitumour immunity. Conversely, cancer cells killed by immunogenic anticancer therapies may stimulate non-homeostatic clearance by antigen-presenting cells and drive cancer antigen-directed immunity. On the other hand, (a general) inflammatory clearance of dying cancer cells could have pro-tumorigenic or antitumorigenic consequences depending on the context. Interestingly, the immunosuppressive consequences that accompany tolerogenic phagocytosis can be reversed through immune-checkpoint therapies. In the present review, we discuss the pivotal role of phagocytosis in regulating responses to anticancer therapy. We give particular attention to the role of phagocytosis following treatment with immunogenic or immune-checkpoint therapies, the clinical prognostic and predictive significance of phagocytic signals for cancer patients and the therapeutic strategies that can be employed for direct targeting of phagocytic determinants.

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Section: Regulated Necrosismentioning

confidence: 78%

Section: Regulated Necrosismentioning

confidence: 99%

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

et al. 2016

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“…Unlabeled BR96 do not have cytotoxic effects on the used cell line in vitro (data not published), but might act via immunologic mechanisms such as ''antibodydependent cell-mediated cytotoxicity'' or ''complement dependent cytotoxicity'' in vivo. 13,21 In the present study, the…”

Section: Discussionmentioning

confidence: 67%

Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with ¹⁷⁷Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model

Eriksson

Ohlsson²,

Nilsson³

et al. 2012

Cancer Biotherapy and Radiopharmaceuticals

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Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ( 177 Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy.

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“…Stimulation of these immune effector cells therefore represents an interesting strategy to improve the therapeutic efficacy of mAbs. The stimulation of natural killer cells, T cells, macrophages, or dendritic cells can be used to enhance antibody-dependent cellular cytotoxicity, phagocytosis or tumor vaccine effects [396]. Besides supporting development and strengthening of the adaptive immunity, therapeutic antibodies are able to trigger early anti-tumor events such as receptor blockade, cytostasis, apoptosis, complement-dependent cytotoxicity and/or antibody-dependent cytotoxicity [397][398][399].…”

Section: Antibodiesmentioning

confidence: 99%

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

Schwendener¹,

Mete²

2013

Frontiers in Clinical Drug Research - Anti-Cancer Agents

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Solid tumors grow within a complex microenvironment composed of diverse cell types such as fibroblasts, endothelial cells, mast cells, macrophages and immune cells that are attracted by tumor cell derived factors and embedded in an extracellular matrix. Molecular and cellular interactions between epithelial cells and cells surrounding the tumor stroma promote growth, invasion and spread of tumors. To delay or impede tumor growth, the tumor microenvironment (TME) is increasingly being explored as a potential therapeutic target for which novel strategies are developed. lt;/pgt;lt;pgt; This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed. This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed.

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Targeting immune effector cells to promote antibody-induced cytotoxicity in cancer immunotherapy

Cited by 55 publications

References 69 publications

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with ¹⁷⁷Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

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Targeting immune effector cells to promote antibody-induced cytotoxicity in cancer immunotherapy

Cited by 55 publications

References 69 publications

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with 177Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

Contact Info

Product

Resources

About

Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with ¹⁷⁷Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model