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[Federal Register Volume 65, Number 122 (Friday, June 23, 2000)]
[Notices]
[Pages 39151-39152]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-15939]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

National Cancer Institute: Development of Innovative Idiotype 
Tumor Vaccines

    Multiple opportunities are available for collaboration with the 
National Cancer Institute (NCI), Division of Clinical Sciences, for the 
pre-clinical and clinical development of protein and/or DNA-based 
idiotypic vaccines using novel formulations, adjuvants or delivery 
systems and directed against low-grade and intermediate B-cell 
lymphomas, mantle cell lymphomas or chronic lymphocytic leukemias 
(CLL). It is anticipated that because of the magnitude and diversity of 
these projects the collaboration(s) will take the form of multiple 
Cooperative Research and Development Agreements (CRADAs). The 
collaboration(s) may involve any aspect of the therapeutic development 
of these tumor vaccines from basic scientific inquiry to late stage 
clinical trials.
AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice of opportunities for Cooperative Research and 
Development Agreements.

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SUMMARY: Pursuant to the Federal Technology Transfer Act of 1986 (FTTA, 
15 U.S.C. 3710; Executive Order 12591 of April 10, 1987 as amended by 
the National Technology Transfer and Advancement Act of 1995), the 
National Cancer Institute (NCI) of the National Institutes of Health 
(NIH) of the Public Health Service (PHS) of the Department of Health 
and Human Services (DHHS) is seeking pharmaceutical or biotechnology 
companies which can effectively collaborate on the scientific and 
commercial development of idiotypic tumor vaccines for treatment of 
low-grade and intermediate B-cell lymphomas, mantle cell lymphoma or 
chronic lymphocytic leukemia (CLL). The goal of the collaboration(s) 
will be the development of novel vaccine strategies to elicit an immune 
response directed against autologous idiotypic surface immunoglobulin 
derived from these tumors. Any CRADA for further development of this 
technology that focuses on preclinical or clinical studies of idiotypic 
vaccines for treatment of the indicated diseases will be considered. 
The CRADA would have an expected duration of three (3) to five (5) 
years. The goals of the CRADA will include the rapid publication of 
research results and timely commercialization of products, diagnostics, 
and treatments that result from the research. The CRADA Collaborators 
will have an option to negotiate the terms of an exclusive or 
nonexclusive commercialization license to subject inventions arising 
under the CRADA.

ADDRESSES: Proposals and questions about this CRADA opportunity may be 
addressed to Dr. Thomas M. Stackhouse, Technology Development & 
Commercialization Branch, National Cancer Institute--Frederick Cancer 
Research and Development Center, Fairview Center, 1003 West Seventh 
Street, Room 502, Frederick, MD 20852, Telephone: (301) 846-5222; 
Facsimile: (301) 846-6820. Scientific Inquiries may be directed to Dr. 
Larry Kwak, M.D., Ph.D., Senior Investigator, Division of Clinical 
Sciences, National Cancer Institute, Bldg. 567, Room 205, Frederick, MD 
21702-1201, Telephone: (301) 846-1607; Facsimile: (301) 846-6107.

EFFECTIVE DATE: Organizations must submit a proposal summary preferably 
two pages or less, to NCI within 90 days from date of this publication. 
Guidelines

[[Page 39152]]

for preparing full CRADA proposals will be communicated shortly 
thereafter to all respondents with whom initial discussions have 
established sufficient mutual interest.

SUPPLEMENTARY INFORMATION:   

Technology Available

    The NCI has established the anti-tumor effects of protein-based 
immunologic anti-idiotype antibodies for lymphoma-specific vaccination 
in both animal studies and human clinical trials evaluating idiotype 
vaccines against B-cell lymphomas. B-cell tumors are composed of 
clonally-expanded cells synthesizing a single antibody molecule 
containing unique variable regions in the heavy and light chains known 
as idiotypic determinants. B-cell lymphomas consist of mature resting 
and reactive lymphocytes, which typically synthesize and express 
immunoglobulin on the cell surface. Idiotypic determinants of the 
surface immunoglobulin of B-cell malignancies therefore, comprise 
tumor-specific antigens that can be used to elicit a specific immune 
response against B-cell lymphoma. Immunization against idiotypic 
determinants on malignant B cells prevents tumor growth and antagonizes 
the growth of established tumors in several syngeneic tumor models. 
Studies conducted at the NCI have also demonstrated that idiotype 
specific immune responses against an autologous antigen could be 
induced in patients with B-cell lymphoma (New Engl. J. of Med. 
327:1209-1215, 1992).
    In a recent clinical study, NCI investigators demonstrated that an 
idiotypic protein vaccine against B-cell lymphoma administered in 
combination with granulocyte-macrophage colony-stimulating factor (GM-
CSF), exerts an anti-tumor effect in patients with B-cell lymphoma as 
measured by the eradication of residual tumor cells bearing a t(14:18) 
translocation detectable by PCR. The clearance of residual tumor cells 
from the blood and the presence of tumor specific cytotoxic T-cells 
correlated with long-term disease free survival in these patients. 
Based on the results of these studies, the NCI is currently conducting 
a definitive multi-center Phase III clinical trial of idiotype vaccines 
against follicular B-cell lymphoma. In addition, results of Phase I/II 
clinical studies evaluating the effectiveness of protein-based 
immnoglobulin idiotype vaccines in the treatment of multiple myeloma 
have also provided support for the use of idiotypic vaccines as a 
cancer therapeutic. The NCI is currently seeking partners to 
collaborate in extending the development of idiotype tumor vaccines to 
additional tumor types specifically, low-grade and intermediate B-cell 
lymphomas, mantle cell lymphoma and chronic lymphocytic leukemia (CLL). 
In addition, the NCI is interested in evaluating novel formulations, 
adjuvants or delivery systems for idiotypic vaccines against any of the 
indicated diseases, including B-cell lymphoma and myeloma.
    The NCI specifically seeks corporate partner(s) with the ability to 
collaborate in the development of any of these therapeutic 
applications. Since idiotypic determinants are tumor-specific, the 
vaccines must be custom-made for each patient. Collaborators will be 
selected based upon the scientific merit and intellectual contributions 
brought to each individual project(s) as well as their demonstrated 
expertise in vaccine production and clinical monitoring. Potential 
collaborators should have experience in preclinical and clinical drug 
development; experience in the monitoring, evaluation and 
interpretation of data from investigational agent clinical studies; or 
experience in areas that represent an extention of these studies to 
include new formulations, or approaches to vaccine delivery, such as 
the development of DNA-based idiotype vaccines.
    The role of the National Cancer Institute in the CRADA(s) may 
include but is not limited to the following:
    1. The NCI will provide intellectual, scientific, and technical 
expertise and experience related to the development of idiotype 
vaccines.
    2. The NCI will continue preclinical and clinical development of 
these vaccines and will make data available to the collaborator as 
appropriate.
    3. NCI will collaborate in the design of experiments and the 
evaluation of results.
    4. Agents developed under a pre-clinical CRADA may proceed to 
clinical development under NCI-sponsored clinical trials if warranted.
    The role of the CRADA Collaborator may include, but is not limited 
to the following:
    1. Providing scientific development strategy and financial and 
other support for the collaborative preclinical development of vaccines 
for new disease indications or for development of novel methodologies.
    2. Providing significant intellectual, scientific, and technical 
expertise or experience to the development of processes required for 
GMP vaccine production of selected vaccine candidates.
    3. Participating in clinical development leading to FDA approval 
and marketing through participation on a Steering Committee established 
to guide the commercialization of successful vaccines.
    Selection criteria for choosing the CRADA Collaborator may include, 
but not be limited to:
    1. The scientific merit and intellectual contribution of the 
Collaborator as outlined in the project proposal. Potential 
collaborators are urged to submit proposals which focus on particular 
areas of expertise and which clearly outline a development and 
commercialization plan.
    2. The ability to collaborate with NCI on the research and 
development of this technology. This ability can be demonstrated 
through experience and expertise in this or related areas that indicate 
the ability to contribute intellectually to the ongoing research and 
development of idiotype vaccines.
    3. The demonstration of adequate resources to perform the research 
and development of this technology (e.g. facilities, personnel and 
expertise) and accomplish objectives according to an appropriate 
timetable to be outlined in the CRADA Collaborator's proposal.
    4. The willingness to commit best effort and demonstrated resources 
to the research and development of this technology, as outlined in the 
CRADA Collaborator's proposal.
    5. The demonstration of expertise in the commercial development and 
production of products related to this area of technology.
    6. The willingness to cooperate with the National Cancer Institute 
in the timely publication of research results.
    7. The agreement to be bound by the appropriate DHHS regulations 
relating to human subjects, and all PHS policies relating to the use 
and care of laboratory animals.

    Dated: June 5, 2000.
Kathleen Sybert,
Chief, Technology Development & Commercialization Branch, National 
Cancer Institute, National Institutes of Health.
[FR Doc. 00-15939 Filed 6-22-00; 8:45 am]
BILLING CODE 4140-01-P
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