Kachlany S.C.,Rutgers University |
Kachlany S.C.,Actinobac Biomed, Inc.
Journal of Investigative Dermatology Symposium Proceedings | Year: 2015
Alopecia areata is an autoimmune condition where activated, pro-inflammatory white blood cells (WBCs) attack the hair follicles, resulting in hair loss. Migration of these activated WBCs from the blood stream and into the follicle tissue requires interaction between the integrin, lymphocyte function-associated antigen-1 (LFA-1) on WBCs, and ICAM-1 on vascular endothelial cells. High levels of active LFA-1 are uniquely expressed on WBCs that are involved in autoimmune and inflammatory conditions. The natural biologic agent LtxA (Leukothera) preferentially targets and depletes disease activated and malignant WBCs by binding to active LFA-1. The experimental drug has demonstrated significant therapeutic efficacy against autoimmune/inflammatory conditions such as psoriasis and allergic asthma in mouse models for these diseases. In addition, when injected into rodents, rhesus macaques, and dogs, LtxA was demonstrated to be physiologically active, biologically specific, and extremely well-tolerated. LFA-1 is an attractive target for therapy because it is only normally present on WBCs and has been shown to be activated and overexpressed on WBCs that are responsible for autoimmune/inflammatory conditions. © 2015 The Society for Investigative Dermatology.
Gupta A.,Rutgers University |
Le A.,Rutgers University |
Belinka B.A.,Actinobac Biomed, Inc. |
Kachlany S.C.,Rutgers University
Leukemia Research | Year: 2011
Leukotoxin (Leukothera™; LtxA) is a bacterial protein and experimental therapeutic that binds leukocyte function antigen (LFA-1) on white blood cells (WBCs) and induces cell death via apoptosis or necrosis. We previously found that LtxA preferentially targets WBCs with high levels of activated LFA-1, which is characteristic of many leukemias and lymphomas, and showed that LtxA exhibits significant anti-leukemia activity in vivo using the humanized SCID mouse model. In this report, we demonstrate that LtxA induces very rapid (1 h) apoptosis in acute monocytic leukemia THP-1 cells characterized by binding of annexin V to cells, loss of mitochondrial membrane potential, depletion of cellular ATP, and fragmentation of chromosomal DNA. We tested the activity of LtxA in combination with the standard chemotherapeutic agents, etoposide, mitoxantrone, daunorubicin, busulfan, and imatinib against several leukemia cell lines, including THP-1, GDM-1, HL-60, and KU-812 cells. LtxA exhibited synergism with all the drugs, and the levels of synergy were dependent on the doses used and cell lines examined. In general, the greatest level of synergy was observed with LtxA and etoposide or imatinib. Combination index (CI) values were less than 0.1 for many of the combinations, indicating very strong synergism. In addition, LtxA alone was cytotoxic to primary cells from newly diagnosed, relapsed, and refractory patients with different hematological malignancies. Thus, LtxA is highly effective at inducing rapid apoptosis both as a single agent and in combination with approved leukemia therapies. © 2011 Elsevier Ltd.
Actinobac Biomed, Inc. and Rutgers University | Date: 2014-06-27
Rutgers University and Actinobac Biomed, Inc. | Date: 2016-03-24
This invention concerns compositions and methods of treating or diagnosing inflammatory disorders and other disorders, as well as compositions and methods of treating HIV.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase II | Award Amount: 1.94M | Year: 2014
DESCRIPTION provided by applicant B cell lymphoma is cancer of B lymphocytes and accounts for more than deaths in the U S each year While many patients respond to currently available therapy there is a high rate of cancer relapse and inability for the patients o tolerate chemotherapy Thus there is a significant need to make available to these patients newer therapies that are more effective and better tolerated than the drugs that are currently used Actinobac Biomed Inc is developing a natural biologic therapy that seeks out and kills a subset of white blood cells WBCs This therapy Leukothera R LtxA leukotoxin is a native protein derived from an oral bacterium LtxA binds specifically to the active form of lymphocyte function associated antigen LFA and causes cell death LFA is found exclusively on WBCs and malignant WBCs overexpress the molecule making them ideal targets for the drug During the phase I stage of this STTR application we showed that LtxA kills malignant B cells using a unique mechanism of action which involves Fas death receptor and caspase lymph node tissue samples from B cell lymphoma patients express high levels of LFA LtxA causes complete regression of tumors in a humanized mouse model for B cell lymphoma and results in long term survival the drug is well tolerated highly active and does not cause a neutralizing immune response in healthy dogs or a dog with naturally occurring lymphoma and we have initiated expression and production of recombinant LtxA in a cGMP drug manufacturing facility in preparation for Investigational New Drug IND enabling studies and clinical trials Important pharmaceutical properties of LtxA include the drug works rapidly in vivo within minutes or less doses as low as g kg have been shown to be highly active in animals neutralizing antibody to LtxA is not generated in healthy or diseased animals even after repeat dosing and the high specificity of the drug allows targeting of a subset of WBCs and complete depletion of WBCs has never been observed with LtxA treatment During this STTR phase II proposal Actinobac will carry out IND enabling studies that will be included in the IND application to the FDA PUBLIC HEALTH RELEVANCE B cell lymphomas kill thousands of people each year We are developing a biotherapeutic agent Leukothera R that has targeted specificity for malignant white blood cells This phase II application will accomplish studies that are required for FDA approval to start testing in human patients with B cell lymphoma
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 202.60K | Year: 2012
DESCRIPTION (provided by applicant): B-cell lymphomas include Hodgkin's, and non-Hodgkin's lymphoma (NHL) (eg. mantle cell lymphoma (MCL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma). More than 70,000 people willbe diagnosed with these B-cell malignancies in the U.S. this year and more than 19,000 will die from NHL alone. B-cell lymphomas can affect numerous organs including the lymph nodes, spleen, liver, and bone marrow. Many patients who receive treatment for B-cell lymphomas become refractory to all available therapies and often die from disease. Thus, there is a significant need to identify newer therapeutics with greater activity and fewer side effects. The novel biologic agent Leukothera(R) (leukotoxin; LtxA) specifically targets active leukocyte function antigen-1 (LFA-1) expressed on white blood cells (WBCs). Malignant WBCs constantly express high levels active LFA-1, allowing LtxA to target specifically diseased cells while minimally affecting healthy cells and tissue. LtxA employs several mechanisms of cell death to intoxicate susceptible WBCs. We have found that cell lines and primary cells from patients with newly diagnosed, relapsed, and refractory leukemia and lymphoma are highly sensitive to LtxA. Inpreclinical studies, LtxA shows significant efficacy using humanized mouse models for leukemia. In addition, single- dose LtxA administered intravenously into rhesus monkeys was active, highly specific for WBCs, and well-tolerated. No effect was seen on red blood cells, platelets, hemoglobin, or markers of organ toxicity. However, no studies have yet examined LtxA for the treatment of B- cell lymphoma. Thus, based on our encouraging preclinical studies for leukemia, we propose to test LtxA using in vitro and in vivo B-cell lymphoma model systems. The data that we generate from the work described in this application is necessary to provide proof-of-principle and mechanistic knowledge for subsequent clinical testing in lymphoma patients. PUBLIC HEALTHRELEVANCE: B-cell lymphomas kill thousands of people each year. We are developing a biotherapeutic agent (leukotoxin) that has targeted specificity for malignant white blood cells. Our studies will test the hypothesis that leukotoxin can be used for the treatment of B-cell lymphomas employing in vitro and in vivo models.
Actinobac Biomed, Inc. | Date: 2014-12-03
A protein agent termed leukotoxin derived from a bacterium used in the manufacture of anti-cancer drugs that has specificity for white blood cells. Pharmaceutical preparations for the treatment of white blood cell diseases in the form of protein agent termed leukotoxin derived from a bacterium that has specificity for white blood cells.
News Article | December 17, 2013
Zach Braff probably has great plans for his 3,105,473 Kickstarter dollars, but crowdfunding can do a lot more than support vanity projects. Enter RocketHub, an online platform that balances typical/questionable business ideas (backpack paintball loader!) with more high-minded pursuits. “Now science can be funded by the people, as opposed to endowments, wealthy patrons, or the government,” says cofounder and CEO Brian Meece. “Even cooler, folks get access to the excitement of making science.” Here, four worthy projects that you can help bring to life. Campaign: Support Production of Leukothera Target: $250,000 Goal: Help Actinobac Biomed complete FDA-mandated studies on this drug that fights diseases and disorders of the immune system, from leukemia to lupus. Swag: N/A Campaign: Whale Call Project Target: $25,000 Goal: Create a Global Ocean App (OApp) to serve as an organizing platform for ocean conservation. Users are encouraged to share and play whale call songs. (Hey, they can’t be any worse than One Direction.) Swag: Twelve-song Whale Call MP3 album ($7 donation) Campaign: AlgaeTown Target: $18,700 Goal: Purchase equipment for this awesomely named Goshen College research project that works to efficiently grow and harvest algae as a fuel and food source. Efficient, nutritious slime! Swag: “Green Citizen” official pin ($15 donation) Campaign: What Are Golden Eagles in Arizona Eating? Target: $1,600 Goal: Support the fieldwork of raptor ecologist/falconer/PhD candidate Michele Losee as she studies the “regurgitated casting material” of these secretive predators. Let’s see Veronica Mars do that. Swag: Name-drop in dissertation acknowledgments
News Article | February 23, 2013
Actinobac Biomed Inc., a North Brunswick, NJ-based developer of pharmaceutical technologies, raised $100k in seed financing. Foundation Venture Capital Group (FVCG), an affiliate of New Jersey Health Foundation, made a follow on investment. It had originally invested $500k when Actinobac was established in 2009. The company intends to use the capital to test its lead product, Leukothera, in the treatment of veterinary white blood cell diseases. Founded by Dr. Scott Kachlany, Actinobac develops pharmaceutical agents for the treatment of hematologic malignancies (leukemias & lymphomas), latent infections (HIV/AIDS & tuberculosis) and autoimmune diseases (rheumatoid arthritis, multiple sclerosis, Crohn’s disease, type 1 diabetes, Lupus & psoriasis) based upon the natural biologic agent leukotoxin (Leukothera™), which targets Leukocyte Function Antigen-1 (LFA-1) on white blood cells. The company has exclusive rights to the therapeutic use of Leukothera™ through a license from the University of Medicine and Dentistry of New Jersey (UMDNJ).