Cell-type specific intracellular payload delivery is desired for antibody-based targeted therapy development. However, tumor-specific internalizing antigens are rare to find, and even rarer for those that are expressed at uniformly high levels. We constructed a bispecific antibody that is composed of a rapidly internalizing antibody binding to a tumor-associated antigen EphA2 and a non-internalizing antibody binding to a highly expressed tumor-associated antigen ALCAM. We found that the overall internalization...
Mon Apr 08, 2019 17:28
One of the most recent advances in the treatment of HER2+ breast cancer is the development of the antibody-drug conjugate, T-DM1. T-DM1 has proven clinical benefits for patients with advanced and/or metastatic breast cancer who have progressed on prior HER2-targeted therapies. However, T-DM1 resistance ultimately occurs and represents a major obstacle in the effective treatment of this disease. Since anti-apoptotic BCL-2 family proteins can affect the threshold for induction of apoptosis and thus...
Mon Apr 08, 2019 17:28
Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, and drug resistance is a major reason for poor outcomes. Elevated proteasome activity plays an important role in NB tumor development and resistance to conventional chemotherapy. Ubiquitin-specific protease 14 (USP14), one of three deubiquitinases associated with the regulatory subunit of the proteasome, is emerging as a potential therapeutic target in multiple tumor types. However, the role of USP14 in NB is yet...
Mon Apr 08, 2019 17:28
Soft tissue sarcomas (STS) represent a heterogeneous group of rare, malignant tumors of mesenchymal origin. Reliable in vivo sarcoma research models are scarce. We aimed to establish and characterize histologically and molecularly stable patient-derived xenograft (PDX) models from a broad variety of STS subtypes. A total of 188 fresh tumor samples from consenting patients with localized or advanced STS were transplanted subcutaneously in NMRI nu/nu immunodeficient mice. Once tumor growth was observed,...
Mon Apr 08, 2019 17:28
While inhibiting EGFR-mediated signaling proved to be effective in treating certain types of cancers, a quickly evolved mechanism that either restores the EGFR signaling or activates an alternative pathway for driving the proliferation and survival of malignant cells limits the efficacy and utility of the approach via suppressing the EGFR functionality. Given the fact that overexpression of EGFR is commonly seen in many cancers, an EGFR-targeting antibody-drug conjugate (ADC) can selectively kill...
Mon Apr 08, 2019 17:28
Recognition of immunoactive oligonucleotides by the immune system, such as Toll-like receptor ligand CpG leads to increased antibody and T cell responses. Systemic application often results in unwanted generalized non-antigen specific activation of the immune system. Nanoparticles are ideal carriers for small and large molecules. Recently, we have demonstrated that calcium phosphate (CaP) nanoparticles functionalized with CpG and viral antigens are able to induce specific T cell immunity that protects...
Mon Apr 08, 2019 17:28
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