Changes in the natural killer cell repertoire and function induced by the cancer immune adjuvant candidate IMMUNEPOTENT-CRP

Lorenzo-Anota, Helen Yarimet; Martínez-Loria, Alan; Taméz-Guerra, Reyes; Scott‐Algara, Daniel; Martínez‐Torres, Ana Carolina; Rodríguez‐Padilla, Cristina

doi:10.1016/j.cellimm.2022.104511

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…Cyclophosphamide is a mainstay chemotherapy for breast cancer; its mechanism of cell death has been explored in several studies, which has been associated with ROS production and caspase-dependent cell death (Emadi and Brodsky et al,2009[ 8 ]; de la Hoz-Camacho et al, 2022[ 7 ]). On the other hand, Immunepotent CRP is a promising immunotherapy which modulates immune cells and induces non-apoptotic regulated cell death (caspase-independent) triggered by ROS production and involving mitochondrial and nuclear alterations in cells from cervical, lung and breast cancer cells, suggesting a conserved mechanism of cell death in solid tumors (Lorenzo-Anota et al, 2022[ 18 ]; Martínez-Torres et al, 2018[ 21 ] and 2019[ 20 ]; Reyes-Ruiz et al, 2021[ 30 ]); however, the cytotoxic effect of ICRP in combination with chemotherapies, including CTX, against breast cancer cells was reported here for the first time.…”

Section: Discussionmentioning

confidence: 99%

The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism

Rivera-Lazarín

Martínez‐Torres

Hoz-Camacho

et al. 2023

EXCLI Journal; 22:Doc131; ISSN 1611-2156

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Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CTX) remains a mainstay in cancer therapy despite harmful adverse effects and cell death-resistances. To face this, combinational therapy of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells. The aim of this study was to evaluate cytotoxicity, the type of cytotoxic effect, and several features involved in cell death induced by the combination of CTX with ICRP (ICRP+CTX) in breast cancer cells as well as their effect on healthy cells. For this purpose, human and murine breast cancer cells, MCF-7, MDA-MB-231 and 4T1, or PBMC were treated for 24 hours with ICRP, CTX or ICRP+CTX in different combination ratios for the assessment of cell death. Flow cytometry and microscopy were used to determine biochemical and morphological characteristics of cell death. Assays showed that ICRP in combination with CTX induce potentiated cell death manifested with morphological changes, loss of mitochondrial membrane potential, reactive oxygen species (ROS) production, and caspase activation. In addition, it was determined that ICRP+CTX-cell death is caspase-independent in all the breast cancer cells assessed. On the other hand, ICRP did not affect CTX-cytotoxicity in PBMC. For all the above, we can propose that the combination of ICRP with CTX an effective combination therapy, promoting their use even in tumoral cells with defects on proteins implicated in the apoptotic pathway.

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Section: Discussionmentioning

confidence: 99%

The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism

Rivera-Lazarín

Martínez‐Torres

Hoz-Camacho

et al. 2023

EXCLI Journal; 22:Doc131; ISSN 1611-2156

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Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.

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Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system

Calvillo-Rodríguez,

Lorenzo-Anota,

Rodríguez-Padilla

et al. 2023

Front. Immunol.

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Cancer immunotherapies include monoclonal antibodies, cytokines, oncolytic viruses, cellular therapies, and other biological and synthetic immunomodulators. These are traditionally studied for their effect on the immune system’s role in eliminating cancer cells. However, some of these therapies have the unique ability to directly induce cytotoxicity in cancer cells by inducing immunogenic cell death (ICD). Unlike general immune stimulation, ICD triggers specific therapy-induced cell death pathways, based on the release of damage-associated molecular patterns (DAMPs) from dying tumour cells. These activate innate pattern recognition receptors (PRRs) and subsequent adaptive immune responses, offering the promise of sustained anticancer drug efficacy and durable antitumour immune memory. Exploring how onco-immunotherapies can trigger ICD, enhances our understanding of their mechanisms and potential for combination strategies. This review explores the complexities of these immunotherapeutic approaches that induce ICD, highlighting their implications for the innate immune system, addressing challenges in cancer treatment, and emphasising the pivotal role of ICD in contemporary cancer research.

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Changes in the natural killer cell repertoire and function induced by the cancer immune adjuvant candidate IMMUNEPOTENT-CRP

Cited by 3 publications

References 57 publications

The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism

The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system

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