Radioimmunotherapy for NHL
Oncolym Backgrounder

February 1998

   Techniclone  Corp.  reported on the status of Oncolym, the  companys most advanced drug development program.

   Oncolym is an investigational radioimmunotherapy being studied   for the treatment of intermediate- and high-grade non-Hodgkins B-cell lymphoma. Techniclone Corp. is dedicated to the rapid and efficient  development and commercialization of Oncolym to improve the quality   of life for those people afflicted with this life-threatening disease. 


   Oncolym, a radiolabeled murine monoclonal antibody, is an   investigational radioimmunotherapy being studied for the treatment of intermediate- and high-grade relapsed or refractory B-cell   non-Hodgkins lymphoma.  Iodine-131 is a radioactive form of iodine.    When radioactive iodine-131 is attached to the Lym-1 antibody, the   result is 131I Lym-1 or Oncolym.  The antibody has a high specificity for human lymphoma cells.  The radiolabeled antibody binds to the tumor after injection and appears to selectively kill the tumor cells by irradiation.   

Preliminary Clinical Results to Date

   To date, 88 patients have been treated with a therapeutic dose of Oncolym. In these trials, patients have achieved meaningful complete and partial remissions of their tumors.  An overall response rate  (complete and partial responses) of 41% has been demonstrated in  patients with intermediate- or high-grade non-Hodgkins lymphoma.   Non-target organ radiation dosimetry demonstrates a tolerable safety  index.  Side effects such as thrombocytopenia (low platelets) and  leukopenia (low white blood cells) have been observed. Clinical   studies have revealed that the side effects appear to be reversible and manageable and to have resolved without complications.   

Current Development Plans

   The current Phase II/III protocol includes all the claims for the intended labeling currently anticipated by Techniclone.  The U.S.   Food and Drug Administration (FDA) will need to review all clinical   data to confirm all findings before Oncolym is cleared for marketing. Oncolym is being investigated as a treatment for patients that have  failed two prior chemotherapy treatments and will be only for  patients with intermediate- or high-grade relapsed or refractory  non-Hodgkins B-cell lymphoma.  Two therapeutic doses of 60 mCi/m2 of radiolabeled Lym-1 given 6-weeks apart will constitute a treatment  cycle.  There are no restrictions for prior chemotherapy regimens and in many cases, patients may be able to be treated in outpatient  facilities rather than in the hospital.  The company continues to remain on schedule to begin multi-center clinical trials in first  quarter 1998.       

Non-Hodgkins Lymphoma (NHL)

   Non-Hodgkins lymphoma is a malignant (cancerous) growth of cells   in the lymph system.  The lymph system is a connecting network of  glands and vessels, which manufacture and circulate lymph throughout  the body.

   According to the American Cancer Society, an estimated 61,000 new cases of lymphoma will be diagnosed, including 7,500 cases of   Hodgkins disease and 54,000 cases of non-Hodgkins lymphoma.  Among   the classified non-Hodgkins lymphoma disease group, approximately 65% of the patient population will be diagnosed with intermediate- or  high-grade lymphoma.

   Prevalence of NHL includes over 200,000 patients in the United   States and the incidence of patients with intermediate- or high-grade lymphomas who will fail chemotherapy and radiation is approximately   40,000.  Oncolym is currently being investigated for treating   intermediate- and high-grade NHL patients from whom current therapy  has proven inadequate, and represents a major unmet medical need.     

Disease Grades

   Non-Hodgkins lymphoma (NHL) is sub-divided into three different   grades based upon specific disease characteristics:  low-grade,  intermediate-grade and high-grade.

   Low-grade lymphoma affects about 35% of the patients newly   diagnosed with the disease.  Low grade lymphoma usually presents as a nodal disease.  In a number of cases, low grade NHL can be indolent   or slow-growing.  Survival from the time of diagnosis with low-grade   disease averages 5 to 7 years. Recent approval of a biologic therapy for low-grade disease was based on a combined overall response of  50%, which was considered similar to conventional therapy.

   Intermediate- and high-grade disease affects some 65% of the   newly diagnosed cases of NHL and has average survival rates of 2-5  years in intermediate and six months to 2 years in high-grade  disease.   Intermediate-and high-grade disease usually presents as a  much more aggressive disease with large extranodal bulky tumors.  The large tumor bulk in intermediate- and high-grade challenges the  development of radioimmunotherapy.     

Lym-1 Antibody

   When radioactive iodine-131 is attached to the Lym-1 monoclonal   antibody, the result is 131I Lym-1 or Oncolym.  The Lym-1 antibody is a murine IgG2a monoclonal antibody (MAb) raised against Raji cells, a malignant line cultured from Burkitts lymphoma.  The Lym-1 antibody   recognizes HLA-Dr10 protein, a cell surface marker present on over  80% of lymphoma cells.  Only about 2% of the normal population have  B-cells that express the HLA-Dr10 marker.  This means that the Lym-1  monoclonal antibody may selectively target lymphoma cancer cells and  may spare healthy B-cells that are responsible for making antibodies  that fight infection.

   In addition, Lym-1 has high precision for its target receptor and may bind 5 times more avidly to lymphoma cells than to healthy cells  that express the HLA-Dr marker.  It is speculated that the HLA-Dr   marker does not modulate (or go away) when treated and it does not  come off the cell during treatment. The antibody profile for Lym-1  demonstrates high specificity only for lymphoma cells and binds to a  very high degree to lymphoma cells rather than healthy cells.

   Numerous other investigations of both non-labeled and   radiolabeled monoclonal antibodies that attach to the CD-20 cell  surface receptor are currently underway.  The CD-20 cell surface   receptor protein is highly expressed on both mature healthy and  lymphoma cells.  As with Lym-1, anti-CD-20 antibodies have a high  precision (or binding avidity) for their target surface receptor.   However, since CD-20 is present on both healthy and lymphoma cells,  therapies targeted at this marker have been shown to kill not only  the lymphoma cells but also the healthy mature B-cells that normally help protect the body from infections.

   Techniclone chose the Lym-1 monoclonal antibody because the   company believes that Lym-1 has the high precision associated with  anti-CD-20 antibodies but also is more specific in recognizing and   attaching to cancer cells while not attaching to healthy  disease-fighting B-cells.

Iodine-131 Radionuclide

   Techniclone Corp. uses iodine-131, a radioactive form of iodine,   attached to the Lym-1 monoclonal antibody.   Techniclone believes that iodine-131 appears to have a number of advantages as a therapeutic  radionuclide.  The primary potential advantage is that beta   irradiation (the energy that kills the cancer) emissions from the  isotope penetrate several millimeters killing some 300 cells around  the antibody.  This makes the radioimmunoconjugate very effective  against the outer rim of cells in the tumor as well as against the bulk of the disease.  It is this outer rim that causes the invasive  damage of the tumor in bulky disease.  Other potential advantages are that iodine is cheap to produce, abundant, requires simple  radiolabeling procedures, has a long half-life, has  well-characterized dosimetry and can be imaged.

   Other radioimmunoconjugates under investigation include   yttrium-90 in combination with a monoclonal antibody to treat  lymphoma.  Techniclone has not pursued yttrium because this isotope   is costly (approximately 10 times that of iodine-131), requires   metal-chelation technology, has a short half-life, can not be imaged  in its therapeutic form, and has such high energy that it may be  less able to kill residual cancer at the tumor site.  In addition,  this higher energy may cause radiation damage to non-targeted tissue  well away from the intended target.        


   The current investigation for the treatment of intermediate- or   high-grade NHL utilizes multiple therapeutic dosing to complete a  treatment course.  Data from a number of clinical trials with Oncolym in intermediate-and high-grade NHL suggest that patients with large  bulky tumor may not respond as well to single doses of radiolabeled  antibody compared to that observed with multiple dose treatments.   This may be in part due to the inability of the limited amount of  beta irradiation and short (a few millimeters) kill radius of  iodine-131 to reach all cells in a large tumor when given as a single dose.  Techniclone believes that radioimmunotherapy for intermediate- and high-grade NHL will require multiple doses to produce clinically  meaningful effects.       

About Techniclone

   Techniclone Corp. is a biotechnology company focused on the research, development and commercialization of novel cancer   therapeutics in two principal areas:  1) direct tumor targeting agents for the therapeutic treatment of refractory malignant lymphomas and  2) collateral targeting agents for the therapeutic treatment of solid tumors.  Oncolym, the companys most advanced drug development  program, is a radiolabled murine monoclonal antibody for the  treatment of intermediate- and high-grade relapsed or refractory   B-cell non-Hodgkins lymphoma.  The company is developing additional   product candidates derived from its collateral targeting program for  solid tumor therapy: Tumor Necrosis Therapy (TNT), Vascular Targeting Agents (VTAs) and Vasopermeation Enhancement Agents (VEAs).  TNT-1 is the first drug candidate to be clinically investigated from its  collateral targeting program and is expected to begin Phase I  clinical trials in first quarter 1998.  Techniclone Corp. intends   to establish strategic partnerships to rapidly develop and  commercialize these products.

   For additional company information, visit the companys Web site at:



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