STUDIES TO IMPROVE CANCER THERAPY WITH ANTIBODIES

  • Meares, Claude F, (PI)
  • Richman, Carol M (PI)
  • Lam, Kit (PI)
  • De Nardo, Sally (PI)
  • O'Donnell, Robert (PI)
  • Colvin, Michael (PI)
  • Denardo, Sally (PI)
  • Hartmann-Siantar, Christine (PI)
  • Lamborn, Kathleen (PI)
  • Larkin, Edward (PI)
  • Salako, Qansy (PI)
  • Gumerlock, Paul (PI)
  • Shen, S.U.I. (PI)
  • Denardo, Sally (PI)
  • Denardo, Gerald (PI)
  • Denardo, Gerald L (PI)

Project: Research project

Description

The objectives of this research are to pursue treatment of cancer
with biologically active radiolabeled MoAb such as Lym-1 and L-6
by examining the influence of basic factors, such as amount of
administered MoAb; amount and schedule for administered
radionuclide; radiation dose rate; alterations to tumor delivery by
preceeding biologic response modifiers, e.g., unlabeled MoAb,
interleukin, interferon or radiation; and site-specific attachments
for toxins. Maximum tolerated dose and optimum biologic dose
will be determined for each system. Treatment of mice and 14
patients with B cell malignancies using I-131 Lym-1, an IgG2a
MoAb has provided evidence for the potential of this and similar
MoAbs and also some of the factors and obstacles that must be
manipulated. Methods to be used include: quantitative imaging
that provides absolute amounts (and concentrations) of MoAb in
tumor and organs for pharmacokinetics and radiation dosimetry in
patients; tomographic imaging estimates of tumor volume; and in
vitro tests for in vivo cytotoxicity. Statistical and protocol
designs which provide the most information from a minimum
number of patients will be used. Response-surface designs may
provide more information that the more commonly used Phase I
design when appropriate to the purpose. Chemical
characterization of the residues of MoAb, such as Lym-1 and L-6
will be used for sitespecific attachment to specific residues of
toxins so as to preserve biologic functions of importance to
treatment of cancer, such as those that determine
immunotargeting and those that stimulate cytotoxic systems in
vivo. Strengths of this program project include: interactive,
interdisciplinary investigative teams established in the 1970's;
investigators who bridge the interface between basic and clinical
sciences; use of methods already established and in some
instances developed by the group; and existence of established
resources and specialized laboratory investigators. While the
investigators choose to pursue radionuclide-conjugated antibodies
as the primary source of therapeutic effect, much of the
information to be obtained is relevant to the use of other toxins
and even antibodies without attached toxins.
StatusFinished
Effective start/end date7/15/883/31/09

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Immunoconjugates
Peptides
Antibodies
Radioimmunotherapy
Peptide Library
Chelating Agents
Prostatic Neoplasms
Breast Neoplasms
Neoplasms
Radiopharmaceuticals
Metals
Monoclonal Antibodies
Therapeutics
Bispecific Antibodies
Organized Financing
Lymphoma
Paclitaxel
Radioactivity
Radio
Radiation

Keywords

  • Medicine(all)