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Multiple Drug Resistance Press release by Immunomedics Corp

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  • Matt960@aol.com
    I saw this press release which came out a few months ago from the Immunomedics corporation. It contains some interesting information about the status of
    Message 1 of 1 , Feb 1, 1998
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      I saw this press release which came out a few months ago from the Immunomedics
      corporation. It contains some interesting information about the status of
      "Multiple Drug Resistance" treatments for cancer therapy and outlines how some
      of them work. --Matt--

      Broad Patent for Therapy and Diagnosis of Drug-Resistant Cancers and
      Infections Awarded to Immunomedics

      New Class of Drugs Specific for Multi-Drug Resistant (MDR) Diseases Invented

      MORRIS PLAINS, N.J., Nov. 11 /PRNewswire/ -- Immunomedics, Inc.
      (Nasdaq: IMMU) today announced the issuance of U.S. Patent 5,686,578, covering
      broad claims for drugs designed to treat and diagnose chemotherapy-resistant
      cancers or infections.
      Drug resistance is a major obstacle to the successful treatment of many
      cancers and infections, such as bacteria and parasites. One important
      mechanism responsible for the resistance developed by many cancers against a
      variety of anti-cancer drugs, even when they have received only one of these,
      is related to the increased expression of certain proteins on the membrane of
      the resistant cells, such as P-glycoprotein. It is generally believed that
      P-glycoprotein is responsible for the cancer cells pumping out the cytotoxic
      cancer drugs, giving rise to multi-drug resistance, or MDR.
      "By constructing targeting drugs that bind to both the multi-drug
      resistant (MDR) protein and also to cancer cells or infectious agents,
      selective delivery of a therapeutic may be achieved. This new technology we
      are developing could offer many new drug groups to circumvent this problem,"
      explained the inventor and Company Chairman, David M. Goldenberg, Sc.D., M.D.
      "One of the major difficulties of treating diseases such as cancers and
      infections is the development of resistance to multiple drugs," stated Dr.
      Goldenberg. "For example, treatment of cancer with doxorubicin can induce the
      P-glycoprotein which pumps the drug from the cancer cells, preventing the drug
      from reaching levels that kill the cancer. Unfortunately, this protein is
      also able to pump many other drugs out of the cancer cells, such as drugs
      which have structures and mechanisms of action different from those of
      doxorubicin."
      The Immunomedics process involves the use of two antibodies fused together
      to result in a bi-specific weapon to target the cancer cells and the
      P-glycoprotein of MDR, simultaneously. Dr. Goldenberg further explained, "By
      constructing specific targeting vehicles that bind both to the protein drug-
      pumps and to cancer cells or infectious agents, selective delivery of a
      therapeutic or diagnostic agent could be possible. These novel targeting
      vehicles could deliver therapeutics such as radioisotopes, anti-cancer drugs,
      antibiotics, antiviral drugs, anti-parasitic drugs, anti-fungal drugs,
      immunomodulators (such as IL-2 or interferon), neutron-capture elements,
      photoactive dyes, chemosensitizers, and enzymes for the activation of
      pro-drugs."
      Another aspect of the invention is to attach diagnostic imaging agents,
      such as radioisotopes, fluorescent labels, photoactive dyes, and
      MRI-chemicals, to the bi-specific drugs for the potential identification of
      tumors that express P-glycoprotein and could thus have MDR. "This may enable
      the earlier diagnosis of MDR tumors that would require other therapeutic
      strategies, possibly also including our bi-specific delivery systems," stated
      Dr. Goldenberg.
      "This technology," Dr. Goldenberg added, "should enable us to diversify
      our diagnostic and therapeutic strategies, both for cancer and certain kinds
      of infection, because related protein families of drug-pumps also have been
      characterized in infectious organisms."
      Marvin E. Jaffe, M.D., Board member of the Company and former President,
      R.W. Johnson Pharmaceutical Research Institute, commented, "We are very
      excited about this novel new technology, which will enable us to diversify our
      strategies for development of new drugs to treat catastrophic diseases."
      The Company stated that because of the very broad scope of this invention,
      it is seeking corporate partners to develop this technology and its diverse
      product opportunities.
      Immunomedics is a biopharmaceutical company focused on the development,
      manufacture and commercialization of diagnostic imaging and therapeutic
      products for the detection and treatment of cancer and infectious diseases.
      Integral to these products are highly specific monoclonal antibodies and
      antibody fragments designed to deliver radioisotopes and chemotherapeutic
      agents to tumors and sites of infection. The Company's first product,
      CEA-Scan(R) for the detection of colorectal cancer, has been approved in the
      United States, Canada, and Europe. The Company's second diagnostic imaging
      product, LeukoScan(R), has been approved for sale in Europe for the diagnosis
      of osteomyelitis (bone infection). This product is presently under regulatory
      review by the U.S. Food and Drug Administration. Immunomedics also has
      several other diagnostic imaging products and two therapeutic products in
      clinical trials.
      This news release contains forward-looking statements that involve risk
      and uncertainties. The development and commercialization of the Company's
      imaging and therapeutic programs and products may differ materially from the
      Company's expectations. Among the factors that could result in a materially
      different outcome are the inherent uncertainties accompanying new product
      development and marketing, actions of regulatory authorities concerning
      product approval, actions of government and private organizations concerning
      reimbursement, the impact of competitive products and pricing, and the results
      of further clinical trials.

      New Hope for Overcoming the Drug Resistance of Cancer Cells

      How Cancers Become Drug-resistant
      The treatment of cancer with cytotoxic drugs is the basis of management of
      patients with tumors that have spread beyond their initial location. This
      cancer spread, or metastasis, is responsible for a very large percent of all
      cancer deaths. Unfortunately, the responses of cancers to chemotherapy vary,
      and failures are usually due to the emergence of a resistance of the cancer
      cells to drugs, particularly at the doses that are tolerated by the patient's
      normal cells and tissues. Yet, cancer chemotherapy, especially the use of
      various drug combinations, has been one of the important developments in
      cancer management in the past 30 years.
      This evolution of drug resistance and its prevention or reversal has been
      a major target of research, both at academic institutions and major drug
      companies for a number of years, and has resulted in the research and use of
      various other drugs and strategies to overcome the resistance of cancer cells
      to the usual cancer drugs.

      Multiple Drug Resistance
      An interesting finding has been that when resistance to one drug occurs, a
      cross-resistance to some related agents as well as to different classes of
      drugs often develops. This cross-resistance to multiple unrelated drugs to
      which the patient's cancer cells were never exposed has been termed multiple
      drug resistance, or MDR. This was first observed in the testing of drugs
      against cancer cells in the test tube over 20 years ago. Subsequently, this
      MDR has been associated with the increased expression of certain proteins on
      the membranes of cancer cells, one of which has been determined to be
      P-glycoprotein. It is generally accepted that P-glycoprotein is the mechanism
      by which drugs are pumped out of the cancer cells, giving rise to MDR.
      Because of this, several major pharmaceutical companies, including the giant
      Swiss drug company, Novartis, are developing drugs to counteract the
      expression and function of P-glycoprotein and similar MDR-related molecules in
      order to increase the retention of cytotoxic drugs in cancer cells. However,
      some of these agents can also affect the P-glycoprotein in normal cells, such
      as cells lining blood vessels, leading to increased toxicity in certain normal
      tissues. In fact, some of these MDR-combating drugs in clinical trials have
      shown a higher toxicity of the conventional cancer drugs being given to the
      patients.

      Overcoming Multiple Drug Resistance With Two-headed Anti-cancer Missiles
      A totally new approach has now been invented by Immunomedics, Inc., a
      biopharmaceutical company located in Morris Plains, New Jersey. Immunomedics
      is a 15-year old publicly traded company of about 100 staff, mostly scientists
      and clinicians, focusing its research on a class of actual and potential
      cancer imaging and therapy drugs that are based upon antibodies that are made
      very selective against cancer cells. In addition, the Company has begun
      building its own contract sales force for marketing its first approved
      products. This week, the U.S. Patent and Trademark Office issued a patent to
      Immunomedics for a new method to overcome drug resistance which also provides
      a way to better detect and treat many forms of cancer which are prone to have
      MDR, and an increased expression of P-glycoprotein.
      The Immunomedics process involves the use of two antibodies fused together
      to result in a specific weapon to target the cancer cells and one of the
      MDR-causes, P-glycoprotein, simultaneously. In this invention, Immunomedics'
      scientists take a cancer-targeting antibody, such as the one in its first
      approved cancer-imaging product, CEA-Scan, and link it to an antibody against
      P-glycoprotein. In earlier studies by other research groups, P-glycoprotein
      antibodies were shown in animals to be effective for killing cancer cells
      having an increased expression of this substance after treatment with drugs
      that induced multiple drug resistance. But since this P-glycoprotein is also
      expressed by some normal cells and tissues of the body, simply using a
      P-glycoprotein antibody alone, Immunomedics' scientists reasoned, would
      increase the toxicity of cancer drugs to many of these normal cells and
      tissues. In order to avoid this, they decided to develop a method to direct
      the P-glycoprotein antibodies only to the cancer cells, and this was done by
      joining the P-glycoprotein antibody to a cancer-targeting antibody. This
      could then increase the delivery of the P-glycoprotein-blocking agent to
      cancer cells, allowing for delivery of various cancer therapeutic agents to
      the cancers bearing P-glycoprotein by also attaching them to this fused, or
      two-headed, antibody missile.
      Since MDR-cancer cells have increased production of P-glycoprotein, the
      scientists further reasoned that these two-headed missiles would have a
      double-target for delivering not only therapeutic agents, such as drugs and
      isotopes, but also imaging agents, such as diagnostic isotopes, dyes, and
      chemicals enhancing magnetic resonance imaging, thus potentially providing a
      whole new category of cancer detection agents. More importantly, these
      imaging agents may help identify tumors having multi-drug resistance, thereby
      avoiding unnecessary drug therapies in favor of other approaches, including
      Immunomedics' new biological therapy.
      The principal inventor of this new technology, Dr. David M. Goldenberg,
      also founder and Chairman of Immunomedics, commented that "this approach is
      totally different from the MDR-interfering drugs under development by the rest
      of the pharmaceutical industry, and should spawn new areas of drug development
      for both cancer detection and therapy, either by blocking multiple drug
      resistance at the outset, or overcoming it thereafter. The bi-specific
      antibody may even be effective without a cancer drug," Dr. Goldenberg added,
      "and we are planning to study this also."
      The Company cautioned that this is still very early research that has not
      yet proceeded to clinical trials, although the anti-cancer antibody has been
      approved when used in conjunction with traditional diagnostic modalities as a
      new colorectal cancer imaging agent in the U.S., Canada, and Europe.

      SOURCE Immunomedics, Inc.



      CONTACT: Cynthia Sullivan, Executive Director of Immunomedics,
      973-605-8200, ext. 109; or Virginia Rybski of Mentus, Inc.,
      619-455-5500

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