Handra ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P529 Background CD47 is over expressed on numerous Serpin B13 Proteins Synonyms various human cancers and it’s also referred to as a “don’t consume me” signal. Several research have demonstrated that there is certainly wonderful prospective for targeting the Contactin-1 Proteins supplier CD47-SIRP pathway as therapy for cancer. Efforts have been produced to create therapies inhibiting the CD47-SIRP pathway, by means of antibodies directed against CD47 and recombinant SIRP proteins. We’ve got developed a novel small molecule CD47 antagonist, AU7R-104, as therapeutic agent for strong and hematological cancers. AU7R-104 enhances phagocytosis of tumor cells and exhibits fantastic drug-like properties with excellent antitumor activity. Right here, we report the in vivo activity of AU7R-104 in distinctive tumor models, biomarker characterization and safety profile of AU7R-104 in rodents and non-rodents. Procedures We’ve identified preclinical candidate compound AU7R-104 with potent in vitro and in vivo activity. AU7R-104 was profiled extensively in diverse tumor models each as single agent and in mixture with tumor distinct antibodies and other anti-cancer agents. In the PK-PD and efficacy studies, efforts have been made for biomarker characterization through multiplex and FACS evaluation. Sophisticated profiling of AU7R-104 has been completed in DMPK and toxicological research in rodents and non-rodents. Outcomes AU7R-104 has potent anti-tumor activity each as a single agent and in combination with anti-cancer agents. In the PK-PD research, AU7R104 enhanced in vivo phagocytosis in both macrophages and dendritic cells. Multiplex evaluation of serum samples indicated there was modulation of macrophage and T-cell mediated cytokines. Inside the advanced ADME assays, AU7R-104 demonstrated very good drug-like properties devoid of any considerable alerts. AU7R- 104 combination treatment options were well tolerated. Preliminary security evaluation of AU7R-104 in each rodents and non-rodents indicated the lack of safety issues typically connected with anti-CD47 antibodies or SIRP-Fc protein therapeutics. Conclusions The above findings support further improvement of these orally bioavailable agents for use within the clinic P530 Novel bispecific antibody targeting NKp30 receptor enhances NKmediated killing activity against a number of myeloma cells and overcomes CD16A deficiency Monia Draghi, PhD1, Jennifer Watkins-Yoon1, Jamie Schafer, PhD1, Sara Haserlat1, Sri Vadde1, Xin Kai1, Allison Nelson1, Lucy Liu1, Nora Zizlsperger, PhD1, Amanda Oliphant1, Michael Schmidt1, Robert Tighe, BS2, 1 Compass Therapeutics, Cambridge, MA, USA; 2Compass Therapeutics LLC, Cambridge, MA, USA Correspondence: Monia Draghi ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):PBackground A number of myeloma (MM) is usually a malignant hematological illness characterized by a dysregulated development of malignant plasma cells. Distinctive therapeutic solutions are available for MM individuals; on the other hand, the illness remains largely incurable. B-cell maturation antigen (BCMA) is a promising target in MM due to its restricted expression in regular and malignant plasma cells [1]. NK cells have been implicated in the clinical efficacy of various therapies against MM and may well contribute to the achievement of stem cell transplantation (SCT) by clearing residual cancer cells [2]. In patients with sophisticated MM, NK cell function is impaired by downregulation of activating receptors which includes NKG2D, 2B4, and CD16A (FcRIIIA) [3,4]. Downregulatio.
