Synergistic Enhancement of Chemotherapy-Induced Cell Death and Antitumor Efficacy against Tumoral T-Cell Lymphoblasts by IMMUNEPOTENT CRP.

T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), present significant challenges to treatment due to their aggressive nature and chemoresistance. Chemotherapies remain a mainstay for their management, but the aggressiveness of these cancers and their associated toxicities pose limitations. Immunepotent CRP (ICRP), a bovine dialyzable leukocyte extract, has shown promise in inducing cytotoxicity against various cancer types, including hematological cancers.

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

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).

p16 and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study.

Background: Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16 are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial.

IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines.

IMMUNEPOTENT CRP (ICRP) is an immunotherapy that induces cell death in cancer cell lines. However, the molecular mechanisms of death are not completely elucidated. Here, we evaluated the implication of intracellular Ca augmentation in the cell death induced by ICRP on T-ALL and breast cancer cell lines.

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

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.

PKHB1, a thrombospondin-1 peptide mimic, induces anti-tumor effect through immunogenic cell death induction in breast cancer cells.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. Recent advances in the field of immuno-oncology demonstrate the beneficial immunostimulatory effects of the induction of immunogenic cell death (ICD). ICD increases tumor infiltration by T cells and is associated with improved prognosis in patients affected by triple negative breast cancer (TNBC) with residual disease.

Evaluation of the Immune Response of a Candidate Phage-Based Vaccine against (Cattle Tick).

Cattle tick () represents a severe problem causing substantial economic losses, estimated in billions of dollars annually. Currently, chemical acaricides represent the most widely used control method. However, several problems such as resistance have been described.

Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status.

(1) Background: Chitosan-coated gold nanoparticles (CH-AuNPs) have important theranostic applications in biomedical sciences, including cancer research. However, although cell cytotoxicity has been studied in cancerous cells, little is known about their effect in proliferating primary leukocytes. Here, we assessed the effect of CH-AuNPs and the implication of ROS on non-cancerous endothelial and fibroblast cell lines and in proliferative lymphoid cells.

The bovine dialysable leukocyte extract IMMUNEPOTENT CRP induces immunogenic cell death in breast cancer cells leading to long-term antitumour memory.

Background: Cancer recurrence is a serious problem in breast cancer (BC) patients, and immunogenic cell death (ICD) has been proposed as a strategy to overcome this recurrence. IMMUNEPOTENT CRP (ICRP) acts as an immunomodulator and can be cytotoxic to cancer cells. Thus, we evaluated if ICRP induces ICD in BC cells.

IMMUNEPOTENT CRP induces DAMPS release and ROS-dependent autophagosome formation in HeLa and MCF-7 cells.

Background: IMMUNEPOTENT CRP (ICRP) can be cytotoxic to cancer cell lines. However, its widespread use in cancer patients has been limited by the absence of conclusive data on the molecular mechanism of its action. Here, we evaluated the mechanism of cell death induced by ICRP in HeLa and MCF-7 cells.

Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines.

Immunotherapies strengthen the immune system to fight multiple diseases such as infections, immunodeficiencies, and autoimmune diseases, and recently, they are being used as an adjuvant in cancer treatment. IMMUNEPOTENT-CRP (I-CRP) is an immunotherapy made of bovine dialyzable leukocyte extract (bDLE) that has chemoprotective and immunomodulatory effects in different cellular populations of the immune system and antitumor activity in different cancer cell lines. Our recent results suggest that the antineoplastic effect of I-CRP is due to the characteristics of cancer cells.

Cytotoxic activity of IMMUNEPOTENT CRP against non-small cell lung cancer cell lines.

Background: IMMUNEPOTENT-CRP® (I-CRP) is a bovine dialyzable leukocyte extract containing transfer factor. It is a cost-effective, unspecific active immunotherapy that has been used in patients with non-small cell lung cancer (NSCLC) as an adjuvant to reduce the side-effects of chemotherapy and radiotherapy, and has shown cytotoxic activity on different cancer cell lines. However, its mechanism of action against lung cancer cells has not been assessed.

Chitosan gold nanoparticles induce different ROS-dependent cell death modalities in leukemic cells.

Background: Nanotechnology proposes the use of gold nanoparticles (AuNPs) for drug delivery, diagnosis, and treatment of cancer. Leukemia is a type of hematopoietic cancer that results from the malignant transformation of white blood cells. Chitosan-coated AuNPs (CH-AuNPs) are cell death inductors in HeLa and MCF-7 cancer cells without affecting peripheral blood mononuclear cells (PBMC).

Homotrimerization Approach in the Design of Thrombospondin-1 Mimetic Peptides with Improved Potency in Triggering Regulated Cell Death of Cancer Cells.

In order to optimize the potency of the first serum-stable peptide agonist of CD47 (PKHB1) in triggering regulated cell death of cancer cells, we designed a maturation process aimed to mimic the trimeric structure of the thrombospondin-1/CD47 binding epitope. For that purpose, an N-methylation scan of the PKHB1 sequence was realized to prevent peptide aggregation. Structural and pharmacological analyses were conducted in order to assess the conformational impact of these chemical modifications on the backbone structure and the biological activity.

Isorhamnetin glycoside isolated from Opuntia ficus-indica (L.) MilI induces apoptosis in human colon cancer cells through mitochondrial damage.

This work aimed to evaluate the mechanisms involved in the apoptosis induction of isorhamnetin-3-O-glucosyl-pentoside (IGP) in metastatic human colon cancer cells (HT-29). To achieve this, we assessed phosphatidylserine (PS) exposure, cell membrane disruption, chromatin condensation, cell cycle alterations, mitochondrial damage, ROS production, and caspase-dependence on cell death. Our results showed that IGP induced cell death on HT-29 cells through PS exposure (48%) and membrane permeabilization (30%) as well as nuclear condensation (54%) compared with control cells.

Inhibitory Effect of Extracts on Murine B16F10 Melanoma and .

() has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells.

PKHB1 Tumor Cell Lysate Induces Antitumor Immune System Stimulation and Tumor Regression in Syngeneic Mice with Tumoral T Lymphoblasts.

Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. Currently, treatment options for patients with relapsed and refractory ALL mostly rely on immunotherapies. However, hematological cancers are commonly associated with a low immunogenicity and immune tolerance, which may contribute to leukemia relapse and the difficulties associated with the development of effective immunotherapies against this disease.

CD47 agonist peptide PKHB1 induces immunogenic cell death in T-cell acute lymphoblastic leukemia cells.

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis derived from its genetic heterogeneity, which translates to a high chemoresistance. Recently, our workgroup designed thrombospondin-1-derived CD47 agonist peptides and demonstrated their ability to induce cell death in chronic lymphocytic leukemia. Encouraged by these promising results, we evaluated cell death induced by PKHB1 (the first-described serum-stable CD47-agonist peptide) on CEM and MOLT-4 human cell lines (T-ALL) and on one T-murine tumor lymphoblast cell-line (L5178Y-R), also assessing caspase and calcium dependency and mitochondrial membrane potential.

Infection and coinfection by human papillomavirus, Epstein-Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study.

Background: Human papillomavirus (HPV) is recognized as an important risk factor for laryngeal carcinogenesis. Although HPV-16 and 18 have been strongly implicated, the presence of other high-risk HPV (HR-HPV) genotypes or the coinfection with Epstein-Barr virus (EBV) or Merkel cell polyomavirus (MCPV) may increase the risk, but their etiological association has not been definitively established.

Methods: We characterized the genotype-specific HPV and the frequency of EBV and MCPV infections through the detection of their DNA in 195 laryngeal specimens of squamous cell carcinoma (SCC) histologically confirmed.

Chitosan gold nanoparticles induce cell death in HeLa and MCF-7 cells through reactive oxygen species production.

Background: Nanotechnology has gained important interest, especially in the development of new therapies; the application of gold nanoparticles (AuNPs) in the treatment and detection of diseases is a growing trend in this field. As cancer represents a serious health problem around the world, AuNPs are studied as potential drugs or drug carriers for anticancer agents. Recent studies show that AuNPs stabilized with chitosan (CH) possess interesting biological activities, including potential antitumor effects that could be selective to cancer cells.

IMMUNEPOTENT CRP induces cell cycle arrest and caspase-independent regulated cell death in HeLa cells through reactive oxygen species production.

Background: Regulated cell death (RCD) is a mechanism by which the cell activates its own machinery to self-destruct. RCD is important for the maintenance of tissue homeostasis and its deregulation is involved in diseases such as cervical cancer. IMMUNEPOTENT CRP (I-CRP) is a dialyzable bovine leukocyte extract that contains transfer factors and acts as an immunomodulator, and can be cytotoxic to cancer cell lines and reduce tumor burden in vivo.

The novel immunomodulator IMMUNEPOTENT CRP combined with chemotherapy agent increased the rate of immunogenic cell death and prevented melanoma growth.

Immunogenic cell death is a cell death modality that stimulates the immune system to combat cancer cells. IMMUNEPOTENT CRP (ICRP) is a mixture of substances of low molecular weight obtained from bovine spleens that exhibits cytotoxic activity on different tumor cell lines and modulates the immune response . The aim of the present study was to determine whether the cytotoxic effect of ICRP and its combination with oxaliplatin (OXP) on murine melanoma B16F10 cells was due to immunogenic cell death.

Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies.

Thrombospondin-1 (TSP-1) is a glycoprotein considered as a key actor within the tumor microenvironment. Its binding to CD47, a cell surface receptor, triggers programmed cell death. Previous studies allowed the identification of 4N1K decapeptide derived from the TSP-1/CD47 binding epitope.

CD47 agonist peptides induce programmed cell death in refractory chronic lymphocytic leukemia B cells via PLCγ1 activation: evidence from mice and humans.

Background: Chronic lymphocytic leukemia (CLL), the most common adulthood leukemia, is characterized by the accumulation of abnormal CD5+ B lymphocytes, which results in a progressive failure of the immune system. Despite intense research efforts, drug resistance remains a major cause of treatment failure in CLL, particularly in patients with dysfunctional TP53. The objective of our work was to identify potential approaches that might overcome CLL drug refractoriness by examining the pro-apoptotic potential of targeting the cell surface receptor CD47 with serum-stable agonist peptides.