PD-1 and CTLA-4 serve as major gatekeepers for effector and cytotoxic T-cell potentiation by limiting a CXCL9/10-CXCR3-IFNγ positive feedback loop.

CXCR3 is a chemokine receptor with three ligands: CXCL9, CXCL10 and CXCL11. We report that in addition to attracting CXCR3+ T cells to tumor sites a key role of CXCL9 and CXCL10 is in inducing a self-feeding feedback loop that accelerates effector/cytotoxic activities of both CD4+ and CD8+ T cells while downregulating immunoregulatory protein TIM3. CXCR3KO mice displayed a markedly reduced response to anti-PD-1 and anti-CTLA-4 therapy.

Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker.

Antibody-drug conjugates (ADCs) are a rapidly expanding class of anticancer therapeutics, with 14 ADCs already approved worldwide. We developed unique linker technologies for the bioconjugation of drug molecules with controlled-release applications. We synthesized cathepsin-cleavable ADCs using a dimeric prodrug system based on a self-immolative dendritic scaffold, resulting in a high drug-antibody ratio (DAR) with the potential to reach 16 payloads due to its dendritic structure, increased stability in the circulation and efficient release profile of a highly cytotoxic payload at the targeted site.

Novel membrane-bound reporter molecule for sorting high producer cells by flow cytometry.

We developed a membrane bound reporter and selection molecule for sorting by fluorescence activated cell sorting (FACS) of cells producing a protein of interest. This molecule is composed of a transmembrane (TM) domain, fused on its extracellular end to a biotin mimetic peptide (BMP) and on its intracellular side to puromycin N-acetyl transferase (PAC). In this format BMP is displayed on the cell membrane surface and PAC faces the cell cytoplasm.

Cytotoxicity of NF-kappaB inhibitors Bay 11-7085 and caffeic acid phenethyl ester to Ramos and other human B-lymphoma cell lines.

Objective: The viability of normal and malignant B-cells was shown to depend on the constitutive activation of the nuclear factor (NF)- kappaB pathway. Thus, attempts to find efficient inhibitors of NF-kappaB play a central role in the search for novel anti-B lymphoma therapies. We studied the effects of two NF-kappaB inhibitors, Bay 11-7085 (BAY) and caffeic acid phenethyl ester (CAPE), on the viability of B-lymphoma cell lines.

Tumor necrosis factor-alpha and CD40L modulate cell surface morphology and induce aggregation in Ramos Burkitt's lymphoma cells.

Interaction of CD40L and its cognate receptor is an essential component of B-lymphocyte signaling, affecting various aspects of B-cell differentiation pathways and immunoglobulin gene expression. However, much less is known about the biological consequences of B-cell signaling through tumor necrosis factor (TNF)-alpha and its cognate receptors TNF-R1 and 2. We used Ramos Burkitt's lymphoma cell line as a model system to study the direct effects of these cytokines on B cells.

Differential effects of tumor necrosis factor-alpha and CD40L on NF-kappa B inhibitory proteins I kappa B alpha, beta and epsilon and on the induction of the Jun amino-terminal kinase pathway in Ramos Burkitt lymphoma cells.

Interaction between the CD40 ligand and its cognate receptor is known to affect various aspects of B-cell biology. Less is known about the biological consequences of B-cell signaling through tumor necrosis factor alpha (TNF-alpha) and its two receptors. We have used Ramos germinal center (GC)-derived Burkitt's lymphoma (BL) cells as a model system to compare some of the early signaling events of TNF-alpha and CD40L on the NF-kappaB and c-Jun amino-terminal kinase (JNK) pathways.