Here are a couple of papers that I ran across and thought that you folks might like to peruse them. First there is a (I think) phase I study of an IDEC anti-melanoma antibody (monoclonal not primatized and uncertain where in pipeline it fits) showing low toxicity and some decent activity though HAMA is found. The second paper simply describes an assay that IDEC uses for functional testing of C2B8 antibody for quality control purposes. Kind of boring but does highlight IDEC's continuing efforts to improve process control of their antibodies and (who knows) might even be a patentable process for the assay of other cytotoxic antibodies.
Ed
Authors
Quan WDY. Dean GE. Spears L. Spears CP. Groshen S. Merritt JA. Mitchell MS .
Title
ACTIVE SPECIFIC IMMUNOTHERAPY OF METASTATIC MELANOMA WITH AN ANTIIDIOTYPE
VACCINE - A PHASE I/II TRIAL OF I-MEL-2 PLUS SAF-M
Source
Journal of Clinical Oncology. 15(5):2103-2110, 1997 May.
Abstract
Purpose: To determine the toxicity and immunologic activity of on antiidiotype melanoma vaccine that consists of
monoclonal antibody I-Mel-2 (MELIMMUNE-5, IDEC Pharmaceuticals, La Jolla, CA) and an immunologic
adjuvant SAF-m. Patients and Methods: Twenty-six patients with metastatic melanoma, whom had previously
received chemotherapy, were given 2 mg of I-Mel-2 and either 100 mu g (n=6) or 250 mu g (n=20) of SAF-m.
Antiidiotype vaccine was given intramuscularly (IM) biweekly for 4 weeks, and then bimonthly until disease
progression. Human antimurine antibodies (HAMA), anti-I-Mel-2 antibodies, and specific antibody (Ab)3 against
the melanoma epitope mimicked by the vaccine were titrated before treatment, biweekly from weeks 4 to 12, and
every 4 to 8 weeks thereafter. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic
resonance imaging (MRI) of the brain were obtained before and bimonthly during treatment to evaluate responses.
Results: Elevated titers of human antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical
antitumor effect (P=.02 and P=.05, respectively). Ab3 wets absent in most patients, but was found in the best
clinical responder. Fever, myalgias/arthralgias, fatigue, nausea, and headaches were the most common toxicities.
Grade III myalgias/arthralgias and headaches required dose reduction of SAF-m in eight patients at the 250-mu g
dose. No treatment-related death occurred. Six patients had an antitumor effect: one complete response in liver and
lung, two minor responses, and three stable disease. The patient with a complete response has survived nearly 5
years. Conclusion: I-Mel-2 antiidiotype vaccine was safe, tolerated best the 100-mu g dose of SAF-m, and had
immunologic and clinical activity. (C) 1997 by American Society of Clinical Oncology. [References: 31]
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Authors
Gazzanosantoro H. Ralph P. Ryskamp TC. Chen AB. Mukku VR .
Title
A NON-RADIOACTIVE COMPLEMENT-DEPENDENT CYTOTOXICITY ASSAY FOR ANTI-CD20
MONOCLONAL ANTIBODY
Source
Journal of Immunological Methods. 202(2):163-171, 1997 Mar 28.
Abstract
A simple and non-radioactive complement-dependent cytotoxicity assay was developed to determine the relative
potency of an anti-CD20 mAb, IDEC-C2B8. The assay measures the relative number of viable cells based on the
uptake and metabolism of the redox dye, Alamar blue. A linear relationship between the relative fluorescence unit
generated and the number of viable cells was demonstrated. The assay is simple, has high throughput (performed
in 96-well microtiter plates), and shows reproducible dose-response curves in the concentration range of 0.02-3.3
mu g/ml. With intra-assay variability of 5-12%, interassay variability of 6-10% and spike recoveries of 101-109%,
the assay has high precision and accuracy. Specificity was demonstrated by the lack of activity of immunoglobulins
that do not bind CD20, or anti-CD20 antibody isotype (gamma 4) which does not bind complement. The assay is
able to detect degradative changes in the molecule caused by heat, light and proteolytic treatments, suggesting its
use as a stability-indicating method. Finally, the Alamar blue method compared favorably with other more
conventional methods used to assess cell viability, The assay has the desired properties for use as a potency assay
for quality control testing of anti-CD20 mAb. [References: 12] |
