Quesions are being asked on other threads about LymphoCide, so some news on its progress will help. Note they are going the IDPH route with a radiolabeled version 90Y-LymphoCide(TM). Maybe they will beat CLTR to market<G>.
Jason
Tuesday May 23, 7:01 am Eastern Time
Company Press Release
SOURCE: Immunomedics, Inc.
Immunomedics Reports Phase II Clinical Results Of
Non-Hodgkin's Lymphoma (NHL) Therapy At American Society Of Clinical
Oncology (ASCO)
NEW ORLEANS, May 23 /PRNewswire/ -- Immunomedics, Inc. (Nasdaq: IMMU - news) today reported that its clinical study
group at Weill Medical College of Cornell University, New York Presbyterian Hospital, presented an analysis of their ongoing
Phase II trial results at the annual meeting of ASCO.
The investigators reported that over 70 patients have been enrolled, with 44 currently assessable for safety and response to
epratuzumab, a humanized monoclonal antibody that targets the CD22 receptor on mature and malignant B-lymphocytes, including
NHL.
``At the optimal weekly infusion of 360-480 mg per square meter, repeated four times, 60% of patients with low-grade, follicular
NHL had an objective response, half of whom were complete responses,'' commented Dr. John Leonard, principal investigator of
the study and Clinical Director of the Center for Lymphoma and Myeloma at New York Presbyterian Hospital.
``In addition, two aggressive NHL patients have also had ongoing complete responses, one lasting over a year and a half in a
patient who was refractory to rituximab (Rituxan©, IDEC/Genentech). We have been particularly pleased that the infusion-related
side effects have been generally minimal and manageable to date, even with infusion times as short as 30-60 minutes,'' he added.
``These updated results of our trials with epratuzumab increase our confidence that this potential therapeutic for NHL may
complement the use of other treatments for NHL, particularly since it has been found, so far, to be safe and well tolerated, and has
a very convenient infusion schedule,'' commented Dr. David M. Goldenberg, Chairman and CEO of the Company. ``We plan to
soon announce our Phase III study plans,'' he added.
``In addition to epratuzumab as a naked antibody, we are progressing in clinical trials with the radiolabeled version,
90Y-LymphoCide(TM), as well as with our solid tumor therapeutic, CEA-Cide(TM),'' Dr. Goldenberg also commented.
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© for the detection of colorectal cancer, is being marketed in
the United States and Europe (approved in Canada). The Company's second diagnostic imaging product, LeukoScan©, is being
marketed in Europe for the diagnosis of osteomyelitis (bone infection). Immunomedics also has several other diagnostic imaging
products and three therapeutic products in clinical trials. The most advanced therapeutic products are LymphoCide(TM)
(epratuzumab), which is completing Phase II clinical trials for the treatment of non-Hodgkin's lymphoma, and CEA-Cide(TM),
which is in Phase I/II clinical trials for the treatment of colorectal, pancreatic, lung, breast, ovarian, and medullary thyroid cancers.
This release, in addition to historical information, contains forward-looking statements made pursuant to the Private Securities
Litigation Reform Act of 1995. Such statements, including the statements regarding future clinical trials, involve significant risks
and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such
differences include, but are not limited to, risks associated with new product development (including clinical trials outcome and
regulatory requirements/actions), competitive risks to marketed products and availability of financing and other sources of capital,
as well as the risks discussed in the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2000.
Company Contact: Cynthia L. Sullivan, Executive Vice President, 973-605-8200, extension 109. Visit the company's web site at
immunomedics.com.
SOURCE: Immunomedics, Inc.
An abstract from Medline
Title
Pharmacokinetics, dosimetry, and initial therapeutic results with 131I- and (111)In-/90Y-labeled
humanized LL2 anti-CD22 monoclonal antibody in patients with relapsed, refractory non-Hodgkin's
lymphoma.
Author
Juweid ME; Stadtmauer E; Hajjar G; Sharkey RM; Suleiman S; Luger S; Swayne LC; Alavi A;
Goldenberg DM
Address
Garden State Cancer Center, Belleville, New Jersey 07109, USA. gscancer@att.net
Source
Clin Cancer Res, 1999 Oct, 5:10 Suppl, 3292s-3303s
Abstract
The pharmacokinetics, dosimetry, and immunogenicity of 131I- and (111)In-/90Y-humanized LL2
(hLL2) anti-CD22 monoclonal antibodies were determined in patients with recurrent non-Hodgkin's
lymphoma. Fourteen patients received tracer doses of 131I-hLL2 followed 1 week later by
therapeutic doses intended to deliver 50-100 cGy to the bone marrow. Another eight patients
received (111)In-hLL2 followed by therapy with 90Y-hLL2 also delivering 50 or 100 cGy to the bone
marrow. The blood T(1/2) (hours) for the tracer infusions of 131I-hLL2 was 44.2 +/- 10.9 (mean +/-
SD) compared with 54.2 +/- 25.0 for the therapy infusions, whereas the values were 70.7 +/- 17.6
for (111)In-hLL2 and 65.8 +/- 15.0 for 90Y-hLL2. The estimated average radiation dose from
131I-hLL2 in tumors >3 cm was 2.4 +/- 1.9 cGy/mCi and was only 0.9-, 1.0-, 1.1-, and 1.0-fold
that of the bone marrow, lung, liver, and kidney, respectively. In contrast, the estimated average
radiation dose from 90Y-hLL2 in tumors >3 cm was 21.5 +/- 10.0 cGy/mCi and was 3.7-, 2.5-,
1.8-, and 2.5-fold that of the bone marrow, lung, liver, and kidney, respectively. No evidence of
significant anti-hLL2 antibodies was seen in any of the patients. Myelosuppression was the only
dose-limiting toxicity and was greater in patients who had prior high-dose chemotherapy.
Objective tumor responses were seen in 2 of 13 and 2 of 7 patients given 131I-hLL2 or 90Y-hLL2,
respectively. In conclusion, 90Y-hLL2 results in a more favorable tumor dosimetry compared with
131I-hLL2. This finding, combined with the initial anti-tumor effects observed, encourage further
studies of this agent in therapeutic trials.
Language of Publication
English
Unique Identifier
20007391
Another Medline abstract of what could be an interesting article
Title
Antibody-targeted therapy for low-grade lymphoma.
Author
Vose JM
Address
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-3332,
USA.
Source
Semin Hematol, 1999 Oct, 36:4 Suppl 6, 15-20
Abstract
Monoclonal antibodies (MoAbs) have now become a successful treatment for selected patients
with non-Hodgkin's lymphoma (NHL). Antibody targets most commonly used for the treatment of
B-cell NHL include CD20, CD19, and CD22. Unconjugated MoAbs are cytotoxic by several
mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent
cell-mediated cytotoxicity (ADCC), and signal transduction leading to apoptosis. In an attempt to
augment the effectiveness of naked antibody preparations, various radioconjugates, immunotoxins,
chemotherapeutic agents, or immune-modifiers have been attached to the antibodies. The
immunotoxin tested most extensively in clinical trials is B4-blocked ricin (anti-CD19 with a
partially blocked ricin toxin). The use of radioimmunoconjugates to augment the effectiveness of
unlabeled antibodies has been one of the most popular strategies. Antibodies against these
targets have now been chelated with radioconjugates such as 131I or 90Y and tested in recent
clinical trials. Radioimmunotherapy has the theoretical advantage over naked antibody therapy or
immunotoxin therapy in that the MoAb conjugated with a radioisotope can have a "cross-fire"
effect such that antigen-negative tumor cells adjacent to those expressing the target antigen may
also be killed. This may enhance the likelihood of tumor sterilization even in fairly bulky disease.
Future studies will focus on testing these antibodies in larger patient populations, sequentially or
in combination, and on combining MoAb therapy with standard- or high-dose chemotherapy and
hematopoietic stem-cell transplantation.
Language of Publication
English
Unique Identifier
99458295
An older review of stuff we already know
Title
Prospects for the management of non-Hodgkin's lymphomas with monoclonal antibodies and
immunoconjugates.
Author
Press OW
Address
Division of Medical Oncology, University of Washington Medical Center, Seattle, Washington
98195-6043, USA.
Source
Cancer J Sci Am, 1998 Jul, 4 Suppl 2:, S19-26
Abstract
PURPOSE: To review the role of monoclonal antibody constructs in the treatment of B-cell
malignancies. PATIENTS AND METHODS: The efficacy and tolerability of unmodified monoclonal
antibodies, immunotoxins, and radioimmunoconjugates have been investigated in patients with
hematologic B-cell malignancies. Response rates, durability of responses, and tolerability were
the principal measures of treatment outcome. RESULTS: Investigators from several institutions
have documented response rates ranging from 25% to 95% in lymphoma patients suffering
relapses who were treated with antibody constructs targeting the CD19, CD20, CD22, DR, or
idiotypic immunoglobulin epitopes on malignant B-cell lymphomas. Chimeric anti-CD20 antibodies
and 131I-labeled anti-CD20 antibodies appear particularly promising, producing response rates of
50% to 95%. Complete remissions (CRs) appear to be more frequent and durable with
radiolabeled anti-CD20 antibodies (33% to 85% CR rate) than with unmodified chimeric anti-CD20
antibodies (6% to 10% CR rate), although a randomized comparison has not yet been made.
CONCLUSION: Monoclonal antibodies provide promising new reagents for the treatment of
patients with B-cell non-Hodgkin's lymphomas. Impressive response rates have been achieved in
clinical trials using unmodified monoclonal antibodies, immunotoxins, and
radioimmunoconjugates, although the durability of responses is still under scrutiny. Durability may
be improved when the antibodies are used in conjunction with chemotherapy or stem cell
transplantation.
Language of Publication
English
Unique Identifier
98336642
An older paper on an important point about CD22 radioimmunotherapy. Anyone know if Y90-lymphocide produces a residualizing radiolabel? I would think so if the D Goldenberg here is the CEO of IMMU.
Title
Advantage of residualizing radiolabels for an internalizing antibody against the B-cell lymphoma
antigen, CD22.
Author
Sharkey RM; Behr TM; Mattes MJ; Stein R; Griffiths GL; Shih LB; Hansen HJ; Blumenthal RD;
Dunn RM; Juweid ME; Goldenberg DM
Address
Garden State Cancer Center, Belleville, NJ 07109, USA.
Source
Cancer Immunol Immunother, 1997 May, 44:3, 179-88
Abstract
LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has a high
sensitivity for detecting B-cell, non-Hodgkin's lymphoma (NHL), as well as an antitumor efficacy in
therapeutic applications. The aim of this study was to determine whether intracellularly retained
radiolabels have an advantage in the diagnosis and therapy of lymphoma with LL2. In vitro studies
showed that iodinated LL2 is intracellularly catabolized, with a rapid release of the radioiodine from
the cell. In contrast, residualizing radiolabels, such as radioactive metals, are retained
intracellularly for substantially longer. In vivo studies were performed using LL2-labeled with
radioiodine by a non-residualizing (chloramine-T) or a residualizing method (dilactitol-tyramine,
DLT), or with a radioactive metal (111In). The biodistribution of a mixture of 125I (non-residualizing
chloramine-T compared to residualizing DLT), 111In-labeled LL2 murine IgG2a or its fragments
[F(ab')2, Fab'], as well as its humanized, CDR-grafted form, was studied in nude mice bearing the
RL human B-cell NHL cell line. Radiation doses were calculated from the biodistribution data
according to the Medical International Radiation Dose scheme to assess the potential advantage
for therapeutic applications. At all assay times, tumor uptake was higher with the residualizing
labels (i.e., 111In and DLT-125I) than with the non-residualizing iodine label. For example,
tumor/blood ratios of 111In-labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing
iodinated IgG on days 3, 7 and 14, respectively. Similar results were obtained for DLT-labeled IgG
and fragments with residualized radiolabels. Tumor/organ ratios also were higher with residualizing
labels. No significant differences in tumor, blood and organ uptake were observed between murine
and humanized LL2. The conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake
values comparable to those of iodinated LL2, the uptake of both antibodies being strongly
dependent on tumor size. These data suggest that, with internalizing antibodies such as LL2,
labeling with intracellularly retained isotopes has an advantage over released ones, which justifies
further clinical trials with residualizing 111In-labeled LL2 for diagnosis, and residualizing 131I and
90Y labels for therapy.
Language of Publication
English
Unique Identifier
97335212
|
