Asunto(s)
Plaquetas/ultraestructura , Diagnóstico por Computador , Errores Diagnósticos , Eritrocitos/parasitología , Malaria/diagnóstico , Microscopía , Adulto , Plaquetas/citología , Tamaño de la Célula , Eritrocitos/ultraestructura , Humanos , Masculino , Plasmodium/aislamiento & purificación , Estudios Retrospectivos , Programas InformáticosRESUMEN
Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.
Asunto(s)
ADP-Ribosil Ciclasa 1/metabolismo , Anticuerpos Monoclonales/uso terapéutico , Mieloma Múltiple/terapia , ADP-Ribosil Ciclasa 1/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Citotoxicidad Celular Dependiente de Anticuerpos , Humanos , Mieloma Múltiple/patología , Microambiente TumoralRESUMEN
Patients with acute lymphoblastic leukemia (ALL) are characterized by an unfavorable outcome in the majority of adult cases. Several clinical trials have confirmed the usefulness of a pediatric-type therapy applied to adult patients. Adults present with higher risk features at diagnosis that predispose them to chemotherapy resistance and disease relapse after an initial achievement of complete remission. The recent introduction of novel immune-targeted therapies, including monoclonal antibodies (MoAbs) targeting B cell-associated antigens such as CD19 (blinatumumab) and CD22 (inotuzumab), tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, bispecific antibodies and chimeric antigen receptor T- cell therapy (CAR-T), circumvent B-ALL cell chemo-refractoriness through novel mechanisms of action, potentially eradicating minimal residual disease (MRD) and enabling more patients to receive allogeneic hematopoietic stem cell transplantation and to achieve a better clinical outcome.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Enfermedad Aguda , Adulto , Anticuerpos Biespecíficos/uso terapéutico , Ensayos Clínicos como Asunto , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Trasplante de Células Madre Hematopoyéticas , Humanos , Imidazoles/uso terapéutico , Inmunoterapia Adoptiva/métodos , Inotuzumab Ozogamicina/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Piridazinas/uso terapéutico , Recurrencia , Lectina 2 Similar a Ig de Unión al Ácido Siálico/antagonistas & inhibidoresRESUMEN
CD22 is a surface molecule expressed early during the ontogeny of B cells in the bone marrow and spleen, and can be found on B cells isolated from the different lymphoid compartments in humans. CD22 is expressed by most blasts from the majority (60-90%) of B-cell acute lymphoblastic leukemia (B-ALL). Current therapies in adults with newly diagnosed B-ALL are associated with complete remission (CR) rates of 50-90%. However, 30-60% of these patients relapse, and only 25-40% achieve disease-free survival of three years or more. Chemotherapy regimens for patients with refractory/relapsed B-ALL are associated with CR rates ranging from 31% to 44%. Novel immune-targeted therapies, such as blinatumomab and inotuzumab (a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic agent calicheamicin), provide potential means of circumventing chemo-refractory B-ALL cells through novel mechanisms of action. Eighty percent of inotuzumab-treated B-ALL patients may achieve a CR state. This review is focused on the biological and clinical activities of CD22 antibodies in B-ALL, and provides evidence about the potential role played by qualitative and quantitative analysis of the CD22 molecule on individual B-ALL blasts in predicting the depletion of leukemic cells, and, ultimately, leading to better clinical response rates.