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Principal Investigator: Priscilla Simon Redd
Organization: CHEMEDIMMUNE, INC.
Fiscal Year: 2024
Award: $320,597
Funding agency: National Cancer Institute
Project Summary
Lung metastasis is the 2nd most common metastasis and accounts for 30% of all metastatic diseases in
human cancer patients. Patients with lung metastases have a very short survival time. For example, the 5-
year survival rate for colorectal cancer patients with lung metastases, if left untreated, is only 5%. Surgical
lung metastases resection (pulmonary metastasectomy) is a “curative” treatment for cancer patients with lung
metastases. For example, pulmonary metastasectomy increases the 5-year survival rate of colorectal cancer
patients with lung metastases from 50.3-66%. However, pulmonary metastasectomy is currently performed
only in a very small population of cancer patients with lung metastases due to the risk-related highly selective
criteria. For example, only 5% of colorectal cancer patients with lung metastases are treated with pulmonary
metastasectomy. A neoadjuvant therapy that can effectively reduce lung metastases number and/or size is
therefore expected to significantly increase the eligible patient population for this life-saving pulmonary
metastasectomy. ChemMedImmune Inc. is developing IFNA2-LNP001, a lipid nanoparticle-encapsulated
IFN2-encoding mini-plasmid DNA for treatment of patients with lung metastases. IFNA2-LNP01 will be
administered in the clinically neoadjuvant setting, where it activates the type I interferon (IFN-I) signaling
pathways in lung metastases to increase the expression of T cell chemokines CXCL9 and CXCL10, resulting
in enhanced T cell recruitment to the tumor site to reduce the size and number of lung metastases. A key
differentiating feature of IFNA2-LNP01 is its administration in the neoadjuvant setting, which is necessary to
give patients the best chance to fight their metastatic tumor ahead of other lines of therapies that can
negatively affect T cells. IFNA2-LNP01 is designed based on our recent published data showing that loss of
IFN-I expression and function is a major mechanism underlying lung metastases immune evasion and growth.
Two aims will be pursued in this project: 1) determine the efficacy of IFNA2-LNP01 in suppression of tumor
lung metastases in vivo; and 2) determine IFNA2-LNP01 biodistribution and toxicology in vivo. This project is
expected to generate sufficient efficacy and toxicology data for a Phase II IND-enabling study of IFNA2-
LNP01.
Terms: <4T1><Abscission><Adverse effects><Affect><B7-H1><B7H1><Biodistribution><CD274><COVID-19><CRG-2><CT-26><CT26><CV-19><CXCL10><CXCL10 gene><CXCL9><CXCL9 gene><Cancer Patient><Cancer Treatment><Cancers><Cell-Mediated Lympholytic Cells><Chemotactic Cytokines><Clinical><Colon Cancer><Colon Carcinoma><Colon Neoplasms><Colon Tumor><Colonic Mass><Colonic Neoplasms><Colonic Tumor><Coronavirus Infectious Disease 2019><Cytolytic T-Cell><Cytotoxic T Cell><Cytotoxic T-Lymphocytes><DNA><Data><Deoxyribonucleic Acid><Development><Disease><Disorder><Dose><Eligibility><Eligibility Determination><Encapsulated><Excision><Extirpation><FDA approved><Frequencies><Generalized Growth><Generations><Growth><Half-Life><Homologous Chemotactic Cytokines><Human><Humig><IFI10><IFNA2><IFNA2 gene><INP10><IP-10><Immune Evasion><Immune mediated therapy><Immunologically Directed Therapy><Immunotherapy><Impairment><Induction Therapy><Intercrines><Interferon Type I><Left><Life><Literature><Lung><Lung Neoplasms><Lung Respiratory System><Lung Tumor><MIG Gene><MOB-1><Macrogols><Malignant Melanoma><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Melanoma><Messenger RNA><Metastasis><Metastasis to the Lung><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Neoplasm to the Lung><Metastatic Tumor><Metastatic Tumor to the Lung><Mice><Mice Mammals><Modeling><Modern Man><Molecular Tumor Suppression><Murine><Mus><Myeloid Cells><NEOADJ><Neoadjuvant><Neoadjuvant Therapy><Neoadjuvant Treatment><Neoplasm Metastasis><Nucleic Acids><Operative Procedures><Operative Surgical Procedures><Organ><PD 1><PD-1><PD-1 blockade><PD-L1><PD1><PD1 blockade><PDL-1><PDL1><PDX model><Pathway interactions><Patient derived xenograft><Patients><Pegintron><Phase><Polyethylene Glycols><Polyethylene Oxide><Polyethyleneoxide><Polymers><Polyoxyethylenes><Population><Programmed Cell Death 1 Ligand 1><Programmed Death Ligand 1><Proteins><Protocol Screening><Publishing><Pulmonary Neoplasms><RNA vaccine><RNA-based vaccine><Recombinant Proteins><Removal><Repression><Risk><SCYB10><SCYB9><SIS cytokines><STAT1><STAT1 gene><STAT91><Secondary Neoplasm><Secondary Tumor><Signal Pathway><Site><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><Survival Rate><T-Cells><T-Lymphocyte><TNBC><Testing><Time><Tissue Growth><Toxicology><Tumor Cell><Tumor Suppression><Tumor Suppressor Proteins><Tumor-Infiltrating Lymphocytes><ViraferonPeg><anti-PD-1 blockade><anti-PD1 blockade><anti-cancer therapy><cancer in the colon><cancer metastasis><cancer therapy><cancer-directed therapy><chemoattractant cytokine><chemokine><colon cancer patients><colon neoplasia><colorectal cancer patients><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><crg-10><curative intervention><curative therapeutic><curative therapy><curative treatments><design><designing><determine efficacy><developmental><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><fighting><gIP-10><human disease><humanized mice><humanized mouse><immune evasive><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><in vivo><induction therapies><killer T cell><lipid based nanoparticle><lipid nanoparticle><lung metastasis><mRNA><mRNA vaccine><mRNA-based vaccine><malignancy><metastasize to the lung><mouse model><murine model><neoplasm/cancer><neoplastic cell><ontogeny><pathway><patient derived xenograft model><patient population><phase 2 study><phase II study><plasmid DNA><polymer><polymeric><programmed cell death 1><programmed cell death ligand 1><programmed cell death protein 1><programmed cell death protein ligand 1><programmed death 1><protein death-ligand 1><pulmonary><pulmonary metastasis><recruit><resection><response to therapy><response to treatment><sle2><success><surgery><systemic lupus erythematosus susceptibility 2><systemic toxicity><therapeutic response><therapy response><thymus derived lymphocyte><treatment response><treatment responsiveness><triple-negative breast cancer><triple-negative invasive breast carcinoma><tumor><tumor cell metastasis><tumor suppressor>