Benson Jr. D.M.,Ohio State University |
Bakan C.E.,Ohio State University |
Mishra A.,Ohio State University |
Hofmeister C.C.,Ohio State University |
And 13 more authors.
T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies.We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti-PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1+ MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered. © 2010 by The American Society of Hematology. Source
Mkrtichyan M.,U.S. National Institutes of Health |
Najjar Y.G.,U.S. National Institutes of Health |
Raulfs E.C.,U.S. National Institutes of Health |
Abdalla M.Y.,U.S. National Institutes of Health |
And 4 more authors.
European Journal of Immunology
Programmed death-1 receptor (PD-1) is expressed on T cells following TCR activation. Binding of this receptor to its cognate ligands, programmed death ligand (PDL)-1 and PDL-2, down-regulates signals by the TCR, promoting T-cell anergy and apoptosis, thus leading to immune suppression. Here, we find that using an anti-PD-1 antibody (CT-011) with Treg-cell depletion by low-dose cyclophosphamide (CPM), combined with a tumor vaccine, induces synergistic antigen-specific immune responses and reveals novel activities of each agent in this combination. This strategy led to complete regression of established tumors in a significant percentage of treated animals, with survival prolongation. We show for the first time that combining CT-011 and CPM significantly increases the number of vaccine-induced tumor-infiltrating CD8 + T cells, with simultaneous decrease in infiltrating Treg cells. Interestingly, we find that CT-011 prolongs Treg-cell inhibition induced by CPM, leading to a sustainable significant synergistic decrease of splenic and tumor-infiltrated Treg cells. Surprisingly, we find that the anti-tumor effect elicited by the combination of CT-011 and CPM is dependent on both CD8 + and CD4 + T-cell responses, although the antigen we used is a class I MHC-restricted peptide. Thus, we describe a novel and effective therapeutic approach by combining multiple strategies to target several tumor-mediated immune inhibitory mechanisms. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source
CureTech | Date: 2014-04-29
A method of treating a tumor or enhancing survival of a subject having a tumor. The method includes (i) administering to a subject in need thereof an effective amount of a humanized monoclonal antibody or a fragment thereof, wherein the antibody or the fragment thereof has all complementarity determining regions of murine monoclonal antibody BAT (mBAT-1) and a framework region (FR) from an acceptor human immunoglobulin, or modified therefrom; and (ii) administering to the subject an effective amount of at least one chemotherapeutic agent selected from the group consisting of: 5-fluorouracil, cytarabine, oxaliplatin, paclitaxel and combinations thereof. The humanized antibody is administered between 1 and 30 days after commencing chemotherapy or substantially simultaneously or concurrently or according to an overlapping schedule with the at least one chemotherapeutic agent to thereby treat the tumor or enhance the survival of the subject having the tumor.
CureTech | Date: 2011-01-04
Surgical and medical instruments and apparatus, namely, syringes for medical purposes, needles for medical purposes, guide wires for medical purposes, probes for medical purposes, drainage tubes for medical purposes, secretion bags for medical purposes, surgical instrument for use in spreading vertebral bodies, surgical instrument for use in delivering stents, disposable medical products, namely, stents, catheters, balloon catheters, surgical implants made of artificial materials, namely, vessel implants, namely, stents for medical purposes and markers for indicating parts of tissue and tumors for medical purposes, application instruments for medical purposes, namely, biopsy punction apparatus, apparatus for introducing bone cement, medical apparatus for breaking up kidney stones, sutures, instruments for the insertion of implants for medical purposes.
CureTech | Entity website
CureTech Ltd. is a biotechnology company developing novel, broad-spectrum, immune modulating products for the treatment and control of cancer ...