A5104384780- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Click Chemistry and Applications
- Diabetes and associated disorders
- Advanced Biosensing Techniques and Applications
- Cell death mechanisms and regulation
- Pancreatic function and diabetes
- CAR-T cell therapy research
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- Diabetes Management and Research
- Peptidase Inhibition and Analysis
- Nanoparticle-Based Drug Delivery
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- Cutaneous Melanoma Detection and Management
- Neuroblastoma Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Ferroptosis and cancer prognosis
CytomX Therapeutics (United States)
2019-2025
Novartis (United States)
2010-2019
Novartis (Switzerland)
2013-2015
Novartis Institutes for BioMedical Research
2013
Molecular Oncology (United States)
2005-2011
Genentech
2007
UCSF Helen Diller Family Comprehensive Cancer Center
2005
Comprehensive Blood & Cancer Center
2003
University of California, San Francisco
2002
University of Colorado Health
1995-1996
The observation that overt type I diabetes is often preceded by the appearance of insulin autoantibodies and reports prophylactic administration to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice, human subjects results in protection from suggest an immune response involved process beta cell destruction. We have recently reported islet-infiltrating cells isolated NOD mice are enriched for insulin-specific T cells, clones capable adoptive transfer diabetes, epitopes...
Increased numbers of tumor-infiltrating macrophages correlate with poor disease outcome in patients affected by several types cancer, including breast and prostate carcinomas. The colony stimulating factor 1 receptor (CSF1R) signaling pathway drives the recruitment tumor-associated (TAMs) to neoplastic microenvironment promotes differentiation TAMs toward a pro-tumorigenic phenotype. Twelve clinical trials are currently evaluating agents that target CSF1/CSF1R as treatment against multiple...
Abstract T cells are known to play an important role in beta cell destruction the nonobese diabetic (NOD) mouse model of Type I diabetes and islet‐specific clones have been demonstrated be capable adoptive transfer diabetes. One issue involves identity antigens that recognized by nominally islet cell‐specific clones. We previously reported insulin‐specific a predominant component isolated from infiltrates pre‐diabetic NOD mice. In this report we examine six independently derived established...
The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels selectivity across the kinome. Herein we report our structure-based optimization strategy a dibenzodiazepine hit 1, discovered in fragment-based screen, yielding highly potent and selective PAK1 such as 2 3. Compound was cocrystallized with to confirm binding an site reveal key interactions. 3 modulated at cellular level due its...
In a transgenic model of multi-stage squamous carcinogenesis induced by human papillomavirus (HPV) oncogenes, infiltrating CD4+ T cells can be detected in both premalignant and malignant lesions. The lymph nodes that drain sites epidermal neoplasia contain activated predominantly reactive toward Staphylococcal bacterial antigens. HPV16 mice deficient were found to have delayed neoplastic progression lower incidence tumors. This delay is marked decreased infiltration neutrophils, reduced...
Abstract Recombinant human rhApo2L/TRAIL selectively stimulates apoptosis in various cancer cells through its receptors DR4 and DR5, is currently clinical trials. Preclinical studies have established antitumor activity of models epithelial cancers; however, efficacy non-Hodgkin lymphoma (NHL) not well studied. Of 7 NHL cell lines tested vitro, stimulated BJAB, Ramos RA1, DoHH-2 cells. Rituximab, a CD20 antibody used to treat certain types NHL, augmented rhApo2L/TRAIL-induced caspase...
Abstract A major agenda for tumor immunology is the generation of specific immune responses leading to destruction incipient and frank neoplasia. In this report, we show that a novel HPV16 E7 fusion protein can produce objective therapeutic against cervical cancer in genetically engineered mice express cervix early region genes implicated as causative agents human cancer. Although nonresponsive toward oncoprotein CD8+ T-cell compartment by virtue MHC haplotype, were capable mounting an...
Post-translational modification catalyzed by phosphopantetheinyl transferases (PPTases) has previously been used to site-specifically label proteins with structurally diverse molecules. PPTase catalysis results in covalent of a serine residue acyl/peptidyl carrier and their surrogate substrates which are typically fused the N- or C-terminus. To test utility PPTases for preparing antibody-drug conjugates (ADCs), we inserted 11 12-mer substrate sequences at 110 constant region loop positions...
Abstract IL-12 is a potent pro-inflammatory cytokine that has shown promising anti-tumor activity through its ability to activate both innate and adaptive immune cells. However, systemically administered limited clinical utility due striking inflammatory toxicity short half-life leading narrow therapeutic margin. Alternative strategies reduce systemic exposure or restrict the tumor microenvironment limit in circulation non-tumor tissues have been explored. Using CytomX proprietary PROBODY®...
It is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction their tumors. Thus, an important goal for immunotherapy identify ways modulate vivo anti-tumor immunity achieve clinical efficacy. We investigate this proposition spontaneous mouse model, Rip1-Tag2. Experimental therapies were carried out two distinctive trial designs, intended either intervene the explosive growth small tumors, or...
Tumor‐associated macrophages can promote growth of cancers. In neuroblastoma, tumor‐associated have greater frequency in metastatic versus loco‐regional tumors, and higher expression genes associated with helps to predict poor prognosis the 60% high‐risk patients who MYCN ‐non‐amplified disease. The contribution cytotoxic T‐lymphocytes anti‐neuroblastoma immune responses may be limited by low MHC class I exonic mutation frequency. Therefore, we modelled human neuroblastoma T‐cell deficient...
Abstract Immune-checkpoint blockade has revolutionized cancer treatment. However, most patients do not respond to single-agent therapy. Combining checkpoint inhibitors with other immune-stimulating agents increases both efficacy and toxicity due systemic T-cell activation. Protease-activatable antibody prodrugs, known as Probody therapeutics (Pb-Tx), localize activity by attenuating capacity bind antigen until protease activation in the tumor microenvironment. Herein, we show that...
Targeted antimitotic agents are a promising class of anticancer therapies. Herein, we describe the development potent and selective Eg5 inhibitor based antibody-drug conjugate (ADC). Preliminary studies were performed using proprietary inhibitors which conjugated onto HER2-targeting antibody maleimido caproyl valine-citrulline para-amino benzocarbamate, or MC-VC-PABC cleavable linker. However, resulting ADCs lacked antigen-specificity in vivo, probably from premature release payload....
Abstract Aberrant activation of osteoclasts due to bone metastasis causes osteolysis, skeletal-related events and severe pain in cancer patients. Macrophage-Colony-stimulating Factor (M-CSF) signaling through its receptor c-fms / Colony-Stimulating Factor-1 Receptor (CSF-1R) the monocytic lineage is essential for osteoclastogenesis, providing an opportunity inhibit this pathway suppress tumor-induced osteolysis. BLZ945 orally active, potent selective CSF-1R inhibitor. inhibits activity with...
Abstract The clinical successes of immunotherapy in immunologically “hot” cancers such as kidney, bladder and lung has lead researchers to pursue strategies improve the initiation immune responses more “cold” breast ovarian cancer. We have characterized two syngeneic mouse models cancer, 4T1 E0771, an cancer model, ID8, for their baseline profile responsiveness various approaches effort enable rational combination therapy. model useful traits immuno-oncology research including a highly...
<h3>Background</h3> Cytokines have been shown to elicit broad anti-tumor activity in preclinical models. These results translated into the approval for clinical use of IFN-alpha and IL-2 before checkpoint therapy era. However, date, success cytokines has limited by systemic toxicity poor exposure. CytomX Therapeutics developed a new class antibodies called Probody<sup>®</sup> therapeutics (Pb-Tx), designed widen therapeutic window minimizing binding targets healthy tissue while being...
Abstract Immune checkpoint blockade therapies have been shown to induce potent and durable anti-tumor immunity in many cancer types. Nevertheless, not all patients benefit from immunotherapy, immune-related adverse events remain a problem. Recently, it has demonstrated that Antibody Drug Conjugates (ADCs) are only capable of killing cells but also can act the immunogenic cell death tumor as well directly activate dendritic cells. These results provided rationale combine ADCs with...
Immune checkpoint blockade therapies have been shown to induce potent and durable anti-tumor immunity in many cancer types. Nevertheless, not all patients benefit from immunotherapy, immune-related adverse events remain a problem. Recently, it has demonstrated that Antibody Drug Conjugates (ADCs) are only capable of killing cells but also can act the immunogenic cell death tumor as well directly activate dendritic cells. These results provided rationale combine ADCs with immunotherapy...