A new tripodal tris(hydroxypyridinone) bifunctional chelator for gallium allows easy production of (68)Ga-labelled proteins rapidly under mild conditions in high yields at exceptionally high specific activity and low concentration.
IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibodydependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen-specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms were undefined and in vivo proof of concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fce receptor system for cancer studies. We also generated rat IgE and IgG mAbs specific for the folate receptor (FRa), which is expressed widely on human ovarian tumors, along with a syngeneic rat tumor model expressing human FRa. Compared with IgG, anti-FRa IgE reduced lung metastases. This effect was associated with increased intratumoral infiltration by TNFa þ and CD80
The 425(scFv)SNAP fusion protein combines rapid and specific targeting of EGFR-positive tumours with a versatile and robust labelling technique that facilitates the attachment of fluorophores for use in optical imaging. The same approach could be used to couple a chelating agent for use in nuclear imaging.
Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic
in nature. While there has been much focus on T cell-mediated immune responses,
limited knowledge exists on the role of mature B cells. We describe an approach,
including a cell-based ELISA, to evaluate mature IgG antibody responses to
melanoma from human peripheral blood B cells. We observed a significant increase
in antibody responses from melanoma patients (n = 10) to
primary and metastatic melanoma cells compared to healthy volunteers
(n = 10) (P<0.0001). Interestingly, we
detected a significant reduction in antibody responses to melanoma with
advancing disease stage in our patient cohort (n = 21)
(P<0.0001). Overall, 28% of
melanoma patient-derived B cell cultures (n = 1,800)
compared to 2% of cultures from healthy controls
(n = 600) produced antibodies that recognized melanoma
cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was
selected for further study. This antibody effectively killed melanoma cells
in vitro via antibody-mediated cellular cytotoxicity. These
data demonstrate the presence of a mature systemic B cell response in melanoma
patients, which is reduced with disease progression, adding to previous reports
of tumor-reactive antibodies in patient sera, and suggesting the merit of future
work to elucidate the clinical relevance of activating humoral immune responses
to cancer.
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