Showing papers by "Jeffrey V. Ravetch published in 2016"
TL;DR: It is found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome, and it is demonstrated that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment.
415 citations
TL;DR: The breadth of reactivity of anti-influenza Abs, regardless of their epitope, necessitates interactions with FcγRs on effector cell populations to mediate in vivo protection, which will guide the design of antiviral Ab therapeutics and inform vaccine design to elicit Abs with optimal binding properties and effector functions.
Abstract: In vivo protection by antimicrobial neutralizing Abs can require the contribution of effector functions mediated by Fc-Fcγ receptor (Fc-FcγR) interactions for optimal efficacy. In influenza, broadly neutralizing anti-hemagglutinin (anti-HA) stalk mAbs require Fc-FcγR interactions to mediate in vivo protection, but strain-specific anti-HA head mAbs do not. Whether this rule applies only to anti-stalk Abs or is applicable to any broadly neutralizing Ab (bNAb) against influenza is unknown. Here, we characterized the contribution of Fc-FcγR interactions during in vivo protection for a panel of 13 anti-HA mAbs, including bNAbs and non-neutralizing Abs, against both the stalk and head domains. All classes of broadly binding anti-HA mAbs required Fc-FcγR interactions to provide protection in vivo, including those mAbs that bind the HA head and those that do not neutralize virus in vitro. Further, a broadly neutralizing anti-neuraminidase (anti-NA) mAb also required FcγRs to provide protection in vivo, but a strain-specific anti-NA mAb did not. Thus, these findings suggest that the breadth of reactivity of anti-influenza Abs, regardless of their epitope, necessitates interactions with FcγRs on effector cell populations to mediate in vivo protection. These findings will guide the design of antiviral Ab therapeutics and inform vaccine design to elicit Abs with optimal binding properties and effector functions.
319 citations
TL;DR: Lu et al. as mentioned in this paper showed that neutralizing antibodies may be a promising therapy for HIV-1 because of their potential to reduce the viral reservoir, and demonstrated that therapeutic antibody treatment enhanced infected individuals' humoral response against the virus.
Abstract: Despite the success of antiretroviral therapy, HIV-1-infected individuals still harbor latent virus. Thus, other therapeutic strategies are needed. A single injection of a broad and potent monoclonal antibody targeting the HIV-1 envelope protein reduced viral loads in HIV-1-infected individuals, albeit only transiently. Lu et al. now report that antibody treatment not only blocked free virus from infecting new cells, it also accelerated the clearance of infected cells. Furthermore, Schoofs et al. demonstrate that therapeutic antibody treatment enhanced infected individuals' humoral response against the virus. Thus, neutralizing antibodies may be a promising therapy for HIV-1 because of their potential to reduce the viral reservoir.
Science , this issue pp. [1001][1] and [997][2]
[1]: /lookup/doi/10.1126/science.aaf1279
[2]: /lookup/doi/10.1126/science.aaf0972
284 citations
TL;DR: These findings highlight the necessity of optimizing the Fc domain for this class of therapeutic antibodies by using appropriate preclinical models that accurately reflect the unique affinities and cellular expression of human FcγR.
130 citations
TL;DR: Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc.
128 citations
TL;DR: This chapter discusses the mechanisms that regulate Fc domain binding to the various types of Fc receptors and provides an overview of the astonishing diversity of effector functions that are mediated through Fc-FcR interactions on myeloid cells.
Abstract: A key determinant for the survival of organisms is their capacity to recognize and respond efficiently to foreign antigens. This is largely accomplished by the orchestrated activity of the innate and adaptive branches of the immune system. Antibodies are specifically generated in response to foreign antigens, facilitating thereby the specific recognition of antigens of almost infinite diversity. Receptors specific for the Fc domain of antibodies, Fc receptors, are expressed on the surface of the various myeloid leukocyte populations and mediate the binding and recognition of antibodies by innate leukocytes. By directly linking the innate and the adaptive components of immunity, Fc receptors play a central role in host defense and the maintenance of tissue homeostasis through the induction of diverse proinflammatory, anti-inflammatory, and immunomodulatory processes that are initiated upon engagement by the Fc domain. In this chapter, we discuss the mechanisms that regulate Fc domain binding to the various types of Fc receptors and provide an overview of the astonishing diversity of effector functions that are mediated through Fc-FcR interactions on myeloid cells. Lastly, we discuss the impact of FcR-mediated interactions in the context of IgG-mediated inflammation, autoimmunity, susceptibility to infection, and responsiveness to antibody-based therapeutics.
92 citations
01 May 2016
TL;DR: It is reported that antibody treatment not only blocked free virus from infecting new cells, it also accelerated the clearance of infected cells and the results indicate that passive immunotherapy can accelerate elimination of HIV-1–infected cells.
32 citations
Patent•
28 Jun 2016TL;DR: In this article, the authors describe a method of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need of such a treatment, provided that the antibody regions are Fc regions with enhanced specificity for FcyRIIb.
Abstract: Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for FcyRIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.
14 citations
Patent•
02 Dec 2016
TL;DR: In this article, the present invention relates to bispecific antibodies and uses thereof, and in particular to Bispecific anti-HIV broadly neutralizing antibodies and their uses.
Abstract: The present invention relates to bispecific antibodies and, in particular, relates to bispecific anti-HIV broadly neutralizing antibodies and uses thereof.
7 citations
TL;DR: It is described that co-inhibition of the adenosingenic pathway through blockade of both CD73 and A2AR enhances antitumor efficacy through distinct mechanisms.
6 citations
Patent•
01 Jun 2016TL;DR: In this article, anti-tumor agents that target certain tumor-associated macrophages were proposed. But, they did not specify the methods of using such agents in treatment of cancer.
Abstract: The present invention relates to anti-tumor agents that target certain tumor-associated macrophages. Also disclosed are methods of using such agents in treatment of cancer.
Patent•
28 Jun 2016
TL;DR: L'invention concerne des anticorps agonistiques ou des parties de liaison a l'antigene associees, qui se lient a la proteine CD40 humaine, presentant une specificite renforcee vis-a-vis de Fc─RIIb.
Abstract: L'invention concerne des anticorps agonistiques ou des parties de liaison a l'antigene associees, qui se lient a la proteine CD40 humaine. Ces anticorps comprennent eventuellement des regions Fc presentant une specificite renforcee vis-a-vis de FcϒRIIb. L'invention concerne egalement des methodes de traitement du cancer ou d'une infection chronique par administration des anticorps de l'invention a un sujet le necessitant.