Novel targeted therapeutic agents for the treatment of childhood, adolescent and young adult non‐Hodgkin lymphoma

Barth, Matthew J.; Minard‐Colin, Véronique

doi:10.1111/bjh.15783

Cited by 7 publications

(10 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the last years, the survival of patients with NHL has increased substantially (4, 5), nevertheless, the development of drug resistance limits the complete success of the treatments (6) and sets the guidelines for the research and development of new antitumor therapies that can completely eradicate drug-resistant transformed cells (7). The drug resistance has been associated mostly to the aberrant inhibition of the signals of intrinsic apoptosis, in which the genes and proteins of the Bcl-2 family play a very important role (8, 9).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Live Attenuated Salmonella enterica Expressing and Releasing Cell-Permeable Bax BH3 Peptide Through the MisL Autotransporter System Elicits Antitumor Activity in a Murine Xenograft Model of Human B Non-hodgkin's Lymphoma

et al. 2019

View full text Add to dashboard Cite

The survival of patients with non-Hodgkin's lymphoma (NHL) has substantially improved with current treatments. Nevertheless, the appearance of drug-resistant cancer cells leads to patient relapse. It is therefore necessary to find new antitumor therapies that can completely eradicate transformed cells. Chemotherapy-resistant cancer cells are characterized by the overexpression of members of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein family, such as Bcl-XL, Bcl-2, and Mcl-1. We have recently shown that peptides derived from the BH3 domain of the pro-apoptotic Bax protein may antagonize the anti-apoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. In this study, we investigated the feasibility of releasing this peptide into the tumor microenvironment using live attenuated Salmonella enterica, which has proven to be an ally in cancer therapy due to its high affinity for tumor tissue, its ability to activate the innate and adaptive antitumor immune responses, and its potential use as a delivery system of heterologous molecules. Thus, we expressed and released the cell-permeable Bax BH3 peptide from the surface of Salmonella enterica serovar Typhimurium SL3261 through the MisL autotransporter system. We demonstrated that this recombinant bacterium significantly decreased the viability and increased the apoptosis of Ramos cells, a human B NHL cell line. Indeed, the intravenous administration of this recombinant Salmonella enterica elicited antitumor activity and extended survival in a xenograft NHL murine model. This antitumor activity was mediated by apoptosis and an inflammatory response. Our approach may represent an eventual alternative to treat relapsing or refractory NHL.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, complete treatment success is limited by the development of drug resistance, a situation with a dire prognosis and with limited possibilities of a cure (6). It is therefore necessary to find new antitumor therapies that can completely eradicate drug-resistant transformed cells (7).…”

Section: Introductionmentioning

confidence: 99%

Live Attenuated Salmonella enterica Expressing and Releasing Cell-Permeable Bax BH3 Peptide Through the MisL Autotransporter System Elicits Antitumor Activity in a Murine Xenograft Model of Human B Non-hodgkin's Lymphoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The creation of an international working group in order to develop clinical trial strategies was recommended. In childhood/adolescent B‐NHL, some selected new agents are under evaluation; they include the identification of new targets, next‐generation MoAb and novel approaches in cellular therapy (Minard‐Colin et al , 2015; Barth et al , 2016; Barth & Minard‐Colin, 2019; Chu et al , 2019; Egan et al , 2019) (Fig 3, Table V).…”

Section: Novel Therapiesmentioning

confidence: 99%

Treatment of relapsed/refractory paediatric aggressive B‐cell non‐Hodgkin lymphoma

2020

View full text Add to dashboard Cite

Summary Aggressive B‐cell non‐Hodgkin lymphoma (B‐NHL) accounts for ≈60% of NHL in children/adolescents. In newly diagnosed Burkitt lymphoma and diffuse large B‐cell lymphoma, short intensive multiagent chemotherapy is associated with a five‐year event‐free survival of around 90%. Very few children/adolescents with aggressive B‐NHL show a relapsed/refractory (r/r) disease. The outcome is poor, with cure rates <30%, and there is no standard of care. Rituximab‐containing salvage regimens may provide a complete/partial response in 60–70% of cases. However, long‐term survival is <10% for non‐transplanted patients. Autologous or allogeneic haematopoietic stem cell transplant is, nowadays, the best option for responding patients, with survival rates around 50%. The benefit of autologous versus allogeneic HSCT is not clear. Numerous novel therapies for r/r B‐NHL are currently being tested in adults, including next‐generation monoclonal antibodies, novel cellular therapy strategies and therapies directed against new targets. Some are under investigation also in children/adolescents, with promising preliminary results.

show abstract

“…Fortunately, conventional treatments such as chemotherapy and radiotherapy have increased 5-year survival to 92% in pediatric patients with acute lymphoblastic leukemias and 91% in pediatric patients with non-Hodgkin's lymphoma [4][5][6]. However, drug resistance hinders the complete success of these therapies [7]; so, new antitumor therapies must be sought that can completely eradicate drug-resistant transformed cells [8].…”

Section: Introductionmentioning

confidence: 99%

Cell-Permeable Bak BH3 Peptide Induces Chemosensitization of Hematologic Malignant Cells

Ugarte-Alvarez

Muñoz-López

Moreno-Vargas

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Hematologic malignancies such as leukemias and lymphomas are among the leading causes of pediatric cancer death worldwide, and although survival rates have improved with conventional treatments, the development of drug-resistant cancer cells may lead to patient relapse and limited possibilities of a cure. Drug-resistant cancer cells in these hematologic neoplasms are induced by overexpression of the antiapoptotic B-cell lymphoma 2 (Bcl-2) protein families, such as Bcl-XL, Bcl-2, and Mcl-1. We have previously shown that peptides from the BH3 domain of the proapoptotic Bax protein that also belongs to the Bcl-2 family may antagonize the antiapoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. Furthermore, cell-permeable Bax BH3 peptides also elicit antitumor activity and extend survival in a murine xenograft model of human B non-Hodgkin’s lymphoma. However, the activity of the BH3 peptides of the proapoptotic Bak protein of the Bcl-2 family against these hematologic malignant cells requires further characterization. In this study, we report the ability of the cell-permeable Bak BH3 peptide to restore apoptosis and induce chemosensitization of acute lymphoblastic leukemia and non-Hodgkin’s lymphoma cell lines, and this event is enhanced with the coadministration of cell-permeable Bax BH3 peptide and represents an attractive approach to improve the patient outcomes with relapsed or refractory hematological malignant cells.

show abstract

Novel targeted therapeutic agents for the treatment of childhood, adolescent and young adult non‐Hodgkin lymphoma

Cited by 7 publications

References 105 publications

Live Attenuated Salmonella enterica Expressing and Releasing Cell-Permeable Bax BH3 Peptide Through the MisL Autotransporter System Elicits Antitumor Activity in a Murine Xenograft Model of Human B Non-hodgkin's Lymphoma

Live Attenuated Salmonella enterica Expressing and Releasing Cell-Permeable Bax BH3 Peptide Through the MisL Autotransporter System Elicits Antitumor Activity in a Murine Xenograft Model of Human B Non-hodgkin's Lymphoma

Treatment of relapsed/refractory paediatric aggressive B‐cell non‐Hodgkin lymphoma

Cell-Permeable Bak BH3 Peptide Induces Chemosensitization of Hematologic Malignant Cells

Contact Info

Product

Resources

About