• Adoptive transfer of T cells transduced with tumor-reactive Chimeric Antigen Receptors (CARs) is a promising strategy for cancer immunotherapy. (biomedcentral.com)
  • A chimeric antigen receptor (CAR) construct was also shown to be integrated in up to 60 percent of T cells. (businesswire.com)
  • There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. (biomedcentral.com)
  • Chimeric antigen receptor (CAR) T cell therapy has emerged as a novel immunotherapy which modifies T cells with CAR, an artificial fusion protein that incorporates an extracellular antigen recognition domain, a transmembrane domain, and an intracellular domain including costimulation and signaling components [ 4 , 5 ]. (biomedcentral.com)
  • Chimeric antigen receptor (CAR) T-cell therapy is a rapidly growing treatment modality. (medscape.com)
  • Chimeric antigen receptors (CARs) are synthetic proteins expressed on the surface of T cells. (medscape.com)
  • ide-cel) as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. (drugs.com)
  • Cilta-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of adults with relapsed or refractory multiple myeloma who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 antibody. (pharmiweb.com)
  • Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 in the U.S. and Europe and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. (pharmiweb.com)
  • Now we have game-changing T-cell-redirecting therapies, such as CAR [chimeric antigen receptor] T-cell therapies and bispecific antibodies," he explained. (onclive.com)
  • Several antigens have been used as targets for CAR-T cell therapy against MM, including B cell maturation antigen (BCMA), CD19, CD138, signaling lymphocytic activation molecule 7 (SLAM7), and immunoglobulin light chains. (biomedcentral.com)
  • Expression of CD38 is tightly regulated during B-cell development and maturation [ 6 ]. (guidetopharmacology.org)
  • Elranatamab is an antibody that binds to both CD3 on T-cells and B-cell maturation antigen (BCMA), which are expressed on the surface of multiple myeloma cells. (medscape.com)
  • Of note, previous treatment with a B-cell maturation antigen (BCMA)-targeted therapy was not allowed in this group of patients. (targetedonc.com)
  • Long-term follow-up from MAJESTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) X CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). (targetedonc.com)
  • Iberdomide demonstrated response rates of approximately 30% as monotherapy in heavily pretreated patients who are triple-class or B-cell maturation antigen refractory. (oncpracticemanagement.com)
  • Participant has previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or B-cell maturation antigen targeted therapy. (who.int)
  • Antibodies to CD38 are useful in subtyping of lymphomas and leukemias, detection of plasma cells (i.e. identification of myelomas), and as a marker for activated B and T cells. (thermofisher.com)
  • Mouse anti-human CD45-FITC (Clone 2D1, Cat No. 347463), Mouse Anti-human CD34-PE [Clone 8G12 (also known as HPCA2), Cat No. 348057], Mouse anti-human CD38-PE-Cy™5 (Clone HIT2, Cat No. 555461) and appropriated isotype control antibodies were purchased from BD Biosciences (San Diego, CA, USA). (researchsquare.com)
  • These anti-CD38 monoclonal antibodies will be blockbuster drugs and an important component of multiple myeloma treatment. (ascopost.com)
  • An investigational class of agents in multiple myeloma, the anti-CD38 monoclonal antibodies, could be the next blockbusters in this malignancy, myeloma experts predicted at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition. (ascopost.com)
  • Anti-CD38 antibodies target multiple myeloma cells by binding to the CD38 antigen expressed on the cell surface and then signaling the patient's immune system to attack the tumor. (ascopost.com)
  • These anti-CD38 monoclonal antibodies, I believe, will be blockbuster drugs and an important component of multiple myeloma treatment," he predicted. (ascopost.com)
  • Since CD38 is expressed in a subset of haematological tumours, particularly in plasma cell tumours such as multiple myeloma (MM), anti-CD38 monoclonal antibodies have been developed with immuno-oncology potential as their main indication. (guidetopharmacology.org)
  • 2. De Weers M, Graus Y, Oprins J, Parren P, Van De Winkel J, Van Vugt M. (2010) Antibodies Against Cd38 For Treatment Of Multiple Myeloma. (guidetopharmacology.org)
  • 1995) Engineered anti-CD38 monoclonal antibodies for immunotherapy of multiple myeloma. (guidetopharmacology.org)
  • Two main advantages of BCMA as an antigen for CAR-T therapy are the potential reduction of on-target/off-tumor toxicity and the lack of antigen-dependent reduction in CAR-T cell expansion [ 16 ]. (biomedcentral.com)
  • The CD38 molecule, with its high and homogenous expression on Multiple Myeloma (MM) cells, appears a suitable target for antibody therapy. (biomedcentral.com)
  • The HIT2 antibody reacts with CD38, an ~45 kDa type II transmembrane glycoprotein expressed by many cell types, especially leukocytes. (stemcell.com)
  • The following product was used in this experiment: CD38 Monoclonal Antibody (90), eFluor™ 450, eBioscience™ from Thermo Fisher Scientific, catalog # 48-0381-82, RRID AB_11218302. (thermofisher.com)
  • Description: The 90 monoclonal antibody reacts with the mouse CD38 molecule, an ~42 kDa type II transmembrane protein. (thermofisher.com)
  • 4-9 Patients with relapsed or refractory multiple myeloma that have been exposed to all three major drug classes (triple-class exposed), including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, tend to demonstrate poor clinical outcomes with very low response rates (20% to 30%), short duration of response (2 to 4 months) and poor survival. (drugs.com)
  • Crystal structure of CD38 with a novel CD38-targeting antibody SAR650984 (=isatuximab). (guidetopharmacology.org)
  • Daratumumab (a MM therapeutic) was the first-in-class anti-CD38 antibody to reach the clinic. (guidetopharmacology.org)
  • However, anti-CD38 monoclonals may have applications in the treatment of diseases in addition to haematological malignancies, including solid tumours and antibody-mediated autoimmune diseases. (guidetopharmacology.org)
  • 2014) SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. (guidetopharmacology.org)
  • Elranatamab is indicated for adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. (medscape.com)
  • It is a bispecific humanized monoclonal antibody against CD3, a T-cell surface antigen, and GPRC5D (human G-protein coupled receptor family C group 5 member D), a tumor-associated antigen with potential antineoplastic activity. (medscape.com)
  • Researchers analyzed data from 165 patients with multiple myeloma who received 3 or more prior lines of therapy including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. (targetedonc.com)
  • The efficacy of a therapeutic antibody depends on the Fab fragment and its binding activity to the target antigen, but also depends on the Fc fragment and its interaction with key Fc receptors.Therefore, candidates must be tested against a panel of receptors during antibody engineering. (acrobiosystems.com)
  • Participant must have received 4 to 6 cycles of induction therapy, which must contain at a minimum an immunomodulatory drugs (IMiD) and a proteasome inhibitor (PI) (with or without anti-CD38 monoclonal antibody) and must have had a single ASCT 80 to 120 days prior to consent. (who.int)
  • Human CD38, a surface molecule expressed by immature and activated T and B lymphocytes, has been characterized as a molecule transducing activation and proliferation signals, and intervening in adhesion to endothelium via its ligand CD31. (nih.gov)
  • The ligand for CD38 is CD31. (biolegend.com)
  • CD38, a counter-receptor for CD31, is an ectoenzyme with cyclase and hydrolase enzymatic activity and is speculated to play a role in lymphocyte activation and differentiation. (thermofisher.com)
  • CD38 is a type II transmembrane glycoprotein and the receptor of CD31. (cusabio.com)
  • The combination of CD38 and CD31 plays an important role in cell migration and receptor-mediated adhesion. (cusabio.com)
  • We investigated the effects of monocyte-activating stimuli (IFN-gamma, IL-2, LPS, TNF-alpha, and GM-CSF) on the expression and function of CD38, starting from the observation that human monocytes and the derived lines U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. (nih.gov)
  • These initial results encouraged us to undertake preclinical investigations with immunotoxins directed against the B-cell restricted CD19 antigen for B-lymphoid tumors and against the CD38 molecule for multiple myeloma. (atsbio.com)
  • CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a Ca+-mobilizing agent. (nih.gov)
  • Treatment with IFN-gamma produced a dose- and time-dependent up-regulation of CD38 in monocytes and monocytic lines, which was paralleled by increased ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities. (nih.gov)
  • CD38 is a 45 kD type II transmembrane ADP-ribosyl cyclase expressed on early hematopoietic precursors and leukocytes, hepatic stellate cells, astrocytes and epithelial cells. (biolegend.com)
  • Bst1 (Bone marrow stromal cell antigen 1, ADP-ribosyl cyclase 2, CD157) is an enzyme that in humans is encoded by the BST1 gene. (wikipedia.org)
  • CD157 and CD38 are both members of the ADP-ribosyl cyclase family of enzymes that catalyze the formation of nicotinamide and adenosine diphosphate ribose (ADPR) or cyclic ADP-ribose (cADPR) from NAD+, although CD157 is a much weaker catalyst than CD38. (wikipedia.org)
  • CD38 is an ectoenzyme (ADP-ribosyl hydrolase) with both cyclase and hydrolase activities, whereby it mediates lymphocyte activation, adhesion and metabolism. (stemcell.com)
  • CD38 functions as a multi-catalytic ectoenzyme serving as ADP-ribosyl cyclase, cyclic ADP-ribose hydrolase and possibly NAD+ glycohydrolase or as a cell surface receptor. (thermofisher.com)
  • CD38 is a gene providing instruction of making a protein named ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (also abbreviated as ADPRC1 or CD38) in human and belongs to ADP-ribosyl cyclase family. (cusabio.com)
  • This compound inhibited kidney ADPR-cyclase activity but not CD38, spleen, heart or brain ADPR-cyclase activity in vitro. (elsevierpure.com)
  • CD38 (NAD+ glycohydrolase) is a type II transmembrane glycoprotein able to induce activation, proliferation and differentiation of mature lymphocytes and mediate apoptosis of myeloid and lymphoid progenitor cells. (thermofisher.com)
  • CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. (guidetopharmacology.org)
  • With this feature, CD38 has become a popular target for the treatment of multiple myeloma (MM). (cusabio.com)
  • Their response involves antigen capture, enhancing their MHC-II presentation receptors and production of chemokines and/or cytokines at the site of inflammation [9]. (fortunejournals.com)
  • Evaluation of Mycobacterium tuberculosis specific antigen-stimulated CD27 - CD38 + IFN-γ + CD4 + T cells for discrimination of active tuberculosis. (bvsalud.org)
  • Although CD38-CAR T cells lysed CD38 + monocytes, NK cells, CD34 + cells and to a lesser extent CD38 + T and B cells, they did not hamper the outgrowth progenitor cells into various myeloid lineages. (biomedcentral.com)
  • Moreover, the CD34 + CD38 - progenitor cells expressed variable amounts of the target receptor CD33, CD133 and c-kit (CD117) [ 20 ]. (researchsquare.com)
  • This is clearly shown in Figure 2, where increasing concentrations of two immunotoxins: anti-CD19 (BU12-Saporin) and anti-CD38 (OKT10-SAP) show decreasing protein synthesis levels in a target CD19+ CD38+ pediatric acute lymphoblastic leukaemia (ALL) cell line. (atsbio.com)
  • The product was purified to obtain the recombinant human CD38 protein carrying C-terminal hFc tag. (cusabio.com)
  • The results showed that both the total CD8+ percentage, and the CD8+CD38+ and CD8+CD38+CD45RO+ subpopulations of cells all individually predicted progression to AIDS. (nih.gov)
  • Prompted by this, we evaluated the feasibility of targeting MM with CD38-CAR-transduced (CD38-CAR) T cells. (biomedcentral.com)
  • Irrespective of the donor, CD38-CAR T cells lost CD38 expression, expanded readily and lysed MM and other malignant cell lines in a cell dose-, and CD38-dependent manner. (biomedcentral.com)
  • Also in a xenotransplant model, i.v. injected CD38-CAR T cells were effective against MM tumors growing in a human bone marrow-like microenvironment, thus demonstrating their ability to properly migrate and infiltrate into the tumor niche to lyse malignant cells. (biomedcentral.com)
  • Furthermore, CD38-CART cells were controllable with a caspase-9-based suicide gene. (biomedcentral.com)
  • These results signify the potential importance of CD38-CAR T cells as therapeutic tools for CD38 + malignancies, including MM, and warrant further safety and efficacy evaluation in appropriate models. (biomedcentral.com)
  • In humans, CD38 is expressed by the majority of hematopoietic cells at levels which vary according to the differentiation and activation status of the cells. (stemcell.com)
  • CD38 is expressed at increasingly higher levels on B cells at each stage of B-cell differentiation, and is then down-regulated on germinal center B cells and mature plasma cells. (thermofisher.com)
  • Crosslinking of CD38 on the surface of mature, resting B cells induces B-cell proliferation, which is enhanced by co-signals such as IL-4 and LPS. (thermofisher.com)
  • Fig. 2: CD38 + CCR7 - CD4 + T cells contain a homogeneous population of IFNγ- and MIP-1β-producing cells. (nature.com)
  • Fig. 3: Analysis of libraries of CD38 + CCR7 - T cell clones and fluorescence barcoding to dissect the antigen-specific repertoire of effector CD4 + T cells. (nature.com)
  • Novel gene editing systems were deployed in NK cells to disrupt CD38 - a cell surface immune modulator that can be targeted in the development of cancer immunotherapy - and to integrate a CAR construct that led to robust CAR-directed cellular cytotoxicity. (businesswire.com)
  • To identify regulators of primitive chronic myeloid leukemia (CML) cells, we performed a high-content cytokine screen using primary CD34 + CD38 low chronic phase CML cells. (haematologica.org)
  • We examined the CD45 dim CD34 + CD38 - CD133 + cells on bone marrow samples of hematologic malignancies and healthy controls using four-color flow cytometry experiments. (researchsquare.com)
  • Interestingly, the CD45 dim CD34 + CD38 - CD133 + cells were highly expressed in bone marrow of patients with AML compared to that of healthy controls (HC). (researchsquare.com)
  • Additionally, the high levels of the CD45 dim CD34 + CD38 - CD133 + cells in AML patients were an independently significant poor risk factor for overall survival and event free survivals. (researchsquare.com)
  • Therefore, our results suggest that CD45 dim CD34 + CD38 - CD133 + cells in AML might have the potential of leukemia stem cells. (researchsquare.com)
  • For examples, Rhenen et al showed that a high percentage of CD34 + CD38 - stem cells at diagnosis significantly correlated with a high minimal residual disease frequency and subsequently to relapse especially after the third course of chemotherapy in AML patients. (researchsquare.com)
  • On the surface of lymphoid cells, myeloid cells and other non-hematopoietic tissue cells, the expression of CD38 shows is lower, but on the surface of malignant plasma cells such as myeloma cells, CD38 shows high expression. (cusabio.com)
  • Hiza H, Hella J, Arbués A, Sasamalo M, Misana V, Fellay J, Gagneux S, Reither K, Portevin D. CD38 expression by antigen-specific CD4 t cells is significantly restored 5 months after treatment initiation independently of sputum bacterial load at the time of tuberculosis diagnosis. (swisstph.ch)
  • Accumulating evidence indicates that ADPR-cyclases other than CD38 are expressed in various cells and organs. (elsevierpure.com)
  • In contrast, the compound did not block CD3/TCR-induced cADPR production and the increase of [Ca 2+ ] i in Jurkat T cells, which express CD38 exclusively. (elsevierpure.com)
  • Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. (ox.ac.uk)
  • In this study, we have used tetrameric major histocompatibility complex-peptide complexes to directly visualize antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (EBV) infection in humans. (ox.ac.uk)
  • We show that massive expansion of activated, antigen-specific T cells occurs during the primary response to this virus. (ox.ac.uk)
  • The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. (ox.ac.uk)
  • After recovery from AIM, the frequency of antigen-specific T cells fell in most donors studied, although populations of antigen-specific cells continued to be easily detectable for at least 3 yr. (ox.ac.uk)
  • As cells undergo oncogenesis, neoantigens are released and captured on major histocompatibility complex (MHC)/ human leukocyte antigen (HLA) of dendritic cells (DCs) that subsequently mature and migrate to central lymphoid organs. (encyclopedia.pub)
  • Immunoprecipitation of CD38 protein from mouse spleen tissue extracts. (cellsignal.com)
  • CD38 is a 45 kD type II transmembrane protein. (biolegend.com)
  • This CD38 protein migrated along the gel to a band of about 58-90 kDa molecular weight. (cusabio.com)
  • A poignant reminder here was the disastrous peripheral nerve damage experienced by women with breast cancer treated with a ricin A chain-based immunotoxin which unexpectedly also targeted nervous tissue.4 The most sensitive in vitro method for determining the selective cytotoxic potency of saporin-based immunotoxins is by measuring their ability to selectively inhibit protein synthesis in antigen-expressing cell lines in a dose-dependent manner. (atsbio.com)
  • Furthermore, it was developed using the basic platform of the CD34 + CD38 - markers, but applying more advanced antigens such as CD45 dim and CD133. (researchsquare.com)
  • These findings identify IFN-gamma as a modulator of monocytic CD38 expression and indicate that CD38 plays a specific role in the activation and adhesion processes performed by monocytes. (nih.gov)
  • Our results indicate that IFN-gamma is a strong up-modulator of CD38, and IL-2 increases its expression only modestly. (nih.gov)
  • CD38 expression can be upregulated upon cell activation. (biolegend.com)
  • Impairment in CD38 expression is associated with immunological and behavioral disorders. (biolegend.com)
  • CUSABIO synthesized the recombinant gene by integrating the C-terminal hFc tag sequence into the targeted gene encoding the 43-300aa of the human CD38. (cusabio.com)
  • They are generated by immunizing an animal with an antigen to elicit an immune response. (cellsignal.com)
  • Our results identify immune-dominant, serovar-specific, and cross-reactive T cell antigens, which should aid in the design of T cell-vaccination strategies against Salmonella . (nature.com)
  • We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. (frontiersin.org)
  • The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. (frontiersin.org)
  • The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. (frontiersin.org)
  • CD157 is a paralog of CD38, both of which are located on chromosome 4 (4p15) in humans. (wikipedia.org)
  • Immunohistochemical analysis of paraffin-embedded mouse spleen using CD38 (E9F5A) XP ® Rabbit mAb (left) compared to concentration-matched Rabbit (DA1E) mAb IgG XP ® Isotype Control #3900 (right). (cellsignal.com)
  • Confocal immunofluorescent analysis of fixed frozen mouse spleen labeled with CD38 (E9F5A) XP ® Rabbit mAb (left, green). (cellsignal.com)
  • Furthermore, CD38 ligation by specific MoAb reduced the IFN-gamma-dependent enhancement of monocyte-dynamic adhesion to endothelial monolayers. (nih.gov)
  • Classical monocyte proliferation and CD38 upregulation on plasmacytoid DCs coincided with declining viral load. (cdc.gov)
  • Examples include daratumumab (Darzalex) and isatuximab (Sarclisa) for CD38 proteins, or elotuzumab ( Empliciti ) for SLAMF7 proteins. (healthline.com)
  • CD38 catalyzes the production of cyclic APD ribose, which is important in Ca 2+ release. (biolegend.com)
  • Diseases associated with CD38 dysfunction include chronic lymphocytic leukemia and Richter's Syndrome. (thermofisher.com)