title: [New immunotherapeutic approaches in oncology and hematology].
abstract: Scientific advances in the last decade have demonstrated the critical role of host immune system in the elimination and suppression of cancer cells. Better knowledge of signaling pathways has enabled the development of new cancer immunotherapy. The discovery of negative feedback mechanisms following the lymphocyte activation has promoted the development of new antibodies targeting molecule inhibitors such as PD1, PDL1 or CTLA-4. Dramatic results were obtained with melanoma. Checkpoint inhibitors (pembrolizumab and ipilimumab) have many advantages in terms of rate of objective response and overall survival. Recent studies in translational research aimed to understand and analyze mechanisms of action of anti-PD1/anti-PDL1. Expression of PDL1 in the tumor is associated with a significantly greater objective response rate (immunohistochemistry). Nevertheless, limits with tumor immunohistochemical analysis encourage new biomarkers research. Other immunotherapy approaches, such as cell and gene therapies using engineered T cells call for further advancements to broaden their applicability. However, these therapies are very expensive and their manufacturing process very restrictive, which could lately limit their use in case of inefficiency of checkpoint inhibitors or when lymphocytic infiltration in tumor is absent. In this case, the objective would be to engineer ex vivo the patient's immune system by restoring the ability of T cells to identify and suppress tumor cells. Currently, two gene-reprogramming tools are under development: chimeric antigen receptor and TCR modified T cells.
authors.affiliation: Service pharmacie, CHRU de Besançon, 3, boulevard Alexandre-Fleming, 25000 Besançon, France; Inserm, unité mixte de recherche 1098, université de Franche-Comté, 8, rue du Docteur Jean-François-Xavier-Girod, 25000 Besançon, France. Electronic address: mkroemer@chu-besancon.fr.
authors.forename: M
authors.initials: M
authors.lastname: Kroemer
authors.affiliation: Inserm, unité mixte de recherche 1098, université de Franche-Comté, 8, rue du Docteur Jean-François-Xavier-Girod, 25000 Besançon, France; Service d'oncologie médicale, CHRU de Besançon, 3, boulevard Alexandre-Fleming, 25000 Besançon, France; Service de chirurgie digestive et de transplantation hépatique, CHRU de Besançon, 3, boulevard Alexandre-Fleming, 25000 Besançon, France.
authors.forename: C
authors.initials: C
authors.lastname: Turco
authors.affiliation: Inserm, unité mixte de recherche 1098, université de Franche-Comté, 8, rue du Docteur Jean-François-Xavier-Girod, 25000 Besançon, France.
authors.forename: J
authors.initials: J
authors.lastname: Galaine
authors.affiliation: Inserm, unité mixte de recherche 1098, université de Franche-Comté, 8, rue du Docteur Jean-François-Xavier-Girod, 25000 Besançon, France.
authors.forename: M
authors.initials: M
authors.lastname: Deschamps
authors.affiliation: Service pharmacie, CHRU de Besançon, 3, boulevard Alexandre-Fleming, 25000 Besançon, France; Inserm, unité mixte de recherche 1098, université de Franche-Comté, 8, rue du Docteur Jean-François-Xavier-Girod, 25000 Besançon, France.
authors.forename: S
authors.initials: S
authors.lastname: Limat
authors.affiliation: Inserm, unité mixte de recherche 1098, université de Franche-Comté, 8, rue du Docteur Jean-François-Xavier-Girod, 25000 Besançon, France; Service d'oncologie médicale, CHRU de Besançon, 3, boulevard Alexandre-Fleming, 25000 Besançon, France.
authors.forename: C
authors.initials: C
authors.lastname: Borg
mesh_terms: D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D000067470:Cellular Reprogramming Techniques / Q000639:trends; D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000639:trends; D006402:Hematologic Diseases / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D016219:Immunotherapy, Adoptive; D058990:Molecular Targeted Therapy / Q000639:trends; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000627:therapeutic use; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D057127:Single-Chain Antibodies / Q000276:immunology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D035703:Therapies, Investigational; D019076:Transgenes; D057170:Translational Research, Biomedical / Q000639:trends
chemical_list: C000605956:CD19-specific chimeric antigen receptor; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies
keywords: Cancer; Checkpoint inhibitors; Chimeric antigen receptor; Immunomodulateurs; Immunotherapy; Immunothérapie; Récepteur antigénique chimérique; TCR modified T cells; TCR transgénique