A diagnosis of ovarian cancer (OvCa) is especially devastating. With 22,240 diagnoses in 2018 and an estimated 14,070 deaths, OvCa has the third-highest mortality rate, leading to the fifth-highest number of cancer deaths among women in the United States. The objective of this research is to validate the anti-tumor function of humanized antibodies with the end goal of identifying and developing an optimized lead monoclonal antibody (mAb) as a therapeutic antibody against Epidermal Growth Factor-Like 6 (EGFL6), a mediator of tumor growth and metastasis. Our first indication for treatment with the therapeutic antibody will be patients with platinum resistant ovarian cancer (OvCa), post-PARP (poly-ADP ribose polymerase) inhibitor treatment, which is a growing area of need. Our proposed therapeutic neutralizes EGFL6 by disrupting its functions to promote cancer cell growth, act as a chemotactic factor in the tumor microenvironment to promote metastasis, and promote angiogenesis. The proposed Phase I research objectives are focused on identifying the antibody most efficacious in inhibiting tumor growth and metastasis for further characterization and development as a therapeutic antibody. Upon successful completion of this Phase I study, the next steps in Phase II will include evaluating toxicity alone as well as efficacy in combination with other OvCa therapeutics in order to address regulatory requirements and refine concepts for clinical trials. Public Health Relevance Statement NARRATIVE The Institute of Medicine (IOM) has concluded that special emphasis is needed to discover novel therapies for high-grade serous cancer (HGSC), such as ovarian cancer (OvCa). However, the benefits of treatment with new cancer drugs remain limited, even with renewed efforts. Our drug development goal is to develop therapeutic monoclonal antibodies (mAb) to disrupt the functions of Epidermal Growth Factor-Like 6 (EGFL6), which has been shown to play an important role in early through late stage ovarian cancer.
Project Terms: Abdomen ; Abdominal ; inhibitor/antagonist ; inhibitor ; Antibodies ; Monoclonal Antibodies ; Clinical Treatment Moab ; mAbs ; Epitopes ; Antigenic Determinants ; Binding Determinants ; malignant breast neoplasm ; Breast Cancer ; malignant breast tumor ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Chemotactic Factors ; Chemoattractants ; Chemotaxins ; complement chemotactic factor ; Clinical Trials ; Complement ; Complement Proteins ; Cessation of life ; Death ; Decision Making ; Diagnosis ; Disease ; Disorder ; Drug resistance ; drug resistant ; resistance to Drug ; resistant to Drug ; Fund Raising ; Goals ; Growth ; Generalized Growth ; Tissue Growth ; ontogeny ; Heart ; Human ; Modern Man ; Incidence ; Institute of Medicine (U.S.) ; Institute of Medicine ; NAS/IOM ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Morbidity - disease rate ; Morbidity ; mortality ; Mus ; Mice ; Mice Mammals ; Murine ; Neoplasm Metastasis ; Metastasis ; Metastasize ; Metastatic Lesion ; Metastatic Mass ; Metastatic Neoplasm ; Metastatic Tumor ; Secondary Neoplasm ; Secondary Tumor ; cancer metastasis ; tumor cell metastasis ; Legal patent ; Patents ; Pathology ; Patients ; Drug Kinetics ; Pharmacokinetics ; Platinum ; Platinum Black ; Pt element ; Play ; Poly(ADP-ribose) Polymerases ; PARP Polymerase ; PARS ; Poly(ADPribose) Polymerase ; poly ADP polymerase ; poly ADP ribose synthetase ; Research ; Research Personnel ; Investigators ; Researchers ; Rights ; Role ; social role ; Signal Transduction ; Cell Communication and Signaling ; Cell Signaling ; Intracellular Communication and Signaling ; Signal Transduction Systems ; Signaling ; biological signal transduction ; Tissues ; Body Tissues ; Toxicology ; Translating ; Transplantation ; transplant ; United States ; Weight ; Woman ; Work ; Treatment Failure ; therapy failure ; base ; Organ ; improved ; Area ; Phase ; Epidermal Growth Factor ; Anthelone U ; Epidermal Growth Factor-Urogastrone ; Urogastrone ; beta-Urogastrone ; Funding ; inhibiting antibody ; Therapeutic ; angiogenesis ; Malignant Cell ; cancer cell ; Diagnostic ; Serous ; intraperitoneal ; Remission ; Disease remission ; experience ; tumor growth ; Toxicities ; Toxic effect ; Modeling ; drug development ; Ig Variable Region ; Immunoglobulin V ; Variable Region ; Immunoglobulin Variable Region ; Malignant Ovarian Neoplasm ; Malignant Ovarian Tumor ; Malignant Tumor of the Ovary ; Ovary Cancer ; ovarian cancer ; Malignant neoplasm of ovary ; Signaling Factor Proto-Oncogene ; Signaling Pathway Gene ; Signaling Protein ; Mediator ; Mediator of Activation ; Mediator of activation protein ; Address ; Affinity ; Data ; in vitro Assay ; in vivo ; Cancer Biology ; Cancer Cell Growth ; Cancer Patient ; Pathologic ; Development ; developmental ; tumor microenvironment ; cancer microenvironment ; humanized monoclonal antibodies ; neutralizing monoclonal antibodies ; neutralizing mAb ; migration ; innovation ; innovate ; innovative ; Resistance ; resistant ; Cancerous ; Therapeutic antibodies ; Therapeutic Monoclonal Antibodies ; MAb Therapeutics ; monoclonal antibody drugs ; therapeutic mAbs ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; stemness ; prototype ; tumor ; humanized antibody ; product development ; phase 1 study ; Phase I Study ; SKOV3 cells ; SKOV3 ; SkOV-3 ; targeted treatment ; targeted drug therapy ; targeted drug treatments ; targeted therapeutic ; targeted therapeutic agents ; targeted therapy ; invention ; novel anticancer drug ; new anti-cancer agent ; new anticancer agent ; new anticancer drug ; new antineoplastic ; new cancer drug ; novel anti-cancer agent ; novel anti-cancer drug ; novel anticancer agent ; novel antineoplastic ; novel cancer drug ; nanomolar ; nano-molar ; cancer subtypes ; cancer sub-types ; stem-like cell ; lead optimization ;
