CZJ@nihcu.bitnet (02/27/89)
Attached is the table of Contents and Items of Interest from
The NIH Guide to Grants and Contracts, Feb 24, 1989.
Jim Cassatt
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Vol. 18, No. 6, February 24, 1989
NOTICES
IMPLEMENTATION OF NEW TERMS AND CONDITIONS OF THE SMALL GRANT
PROGRAM ..............................................(84/122)............... 1
Alcohol, Drug Abuse, and Mental Health Administration
Index: ALCOHOL, DRUG ABUSE, MENTAL HEALTH
DATED ANNOUNCEMENTS (RFPs AND RFAs)
PHASE III TRIAL OF NICHD-DEVELOPED PERTUSSIS VACCINE (SOURCES SOUGHT)........ 1
National Institute of Child Health and Human Development (128/190)
Index: CHILD HEALTH, HUMAN DEVELOPMENT
COMBINED ENDPOINT MOUSE GERM CELL MUTAGENICITY ASSAY (RFP) ..(193/228)....... 2
National Institute of Environmental Health Sciences
Index: ENVIRONMENTAL HEALTH SCIENCES
LOW-DOSE ORAL CONTRACEPTIVES AND CARDIOVASCULAR DISEASE (RFP) ..(241/271).... 3
National Institute of Child Health and Human Development
Index: CHILD HEALTH, HUMAN DEVELOPMENT
LEADERSHIP AND EXCELLENCE IN ALZHEIMER'S DISEASE (LEAD) AWARD (RFA) ......... 3
National Institute on Aging (274/369)
Index: AGING
ONGOING PROGRAM ANNOUNCEMENTS
SPECIFIC CANCER CELL TARGETING USING MOLECULAR GENETIC TECHNOLOGY ........... 4
National Cancer Institute (374/524)
Index: CANCER
REGULATION OF PROSTATIC INVOLUTION AS RELATED TO PROSTATIC CANCER ........... 6
National Cancer Institute (527/663)
Index: CANCER
ALZHEIMER'S DISEASE AND RELATED DISORDERS: ISSUES IN CAREGIVING ............ 8
National Institute on Aging (666/920)
National Center for Nursing Research
National Institute of Mental Health
National Center for Health Services Research
Index: AGING, NURSING RESEARCH, MENTAL HEALTH, HEALTH SERVICES RESEARCH
SMALL GRANT PROGRAM .......................................(923/1119)........11
Alcohol, Drug Abuse, and Mental Health Administration
Index: ALCOHOL, DRUG ABUSE, MENTAL HEALTH
SPECIFIC CANCER CELL TARGETING USING MOLECULAR GENETIC TECHNOLOGY
P.T. 34; K.W. 0715035, 1002058, 0760045, 0760080, 1007009
National Cancer Institute
Application Receipt Dates: February 1, June 1, October 1
The Developmental Therapeutics Program (DTP) and the Biological Response
Modifiers Program (BRMP), Division of Cancer Treatment (DCT) of the National
Cancer Institute (NCI) invite grant applications from interested investigators
for basic and applied molecular biological studies concerned with specific
targeting of cancer cells. The goal is to develop and evaluate novel methods
for killing tumor cells while sparing normal cells in vivo.
BACKGROUND
Specific targeting of cytotoxic agents to tumor cells and not to normal cell
populations continues to be a major goal in the treatment of cancer. Although
many cytotoxic agents are effective against rapidly dividing cells such as in
leukemia, where a large percentage of the tumor cell population is undergoing
proliferation, these same agents cause undesirable toxicity often associated
with damage to normal rapidly proliferating cells such as those in the bone
marrow and the gastrointestinal tract. Approaches have been taken to achieve
Vol. 18, No. 6, February 24, 1989 - Page 4
specificity of cancer treatment by exploiting unique features of the tumor
type. Immunotoxin (a specific antibody covalently coupled to a toxin) therapy
has the theoretical capability of restricting cell killing to a defined
antigen-bearing cell population, but several problems have been identified
which may limit the use of this technique. These problems include the rapid
emergence of non-antigenic variants within a tumor, the shedding of antigens
from the tumor surface, and the development of a human anti-immunoglobulin
response. Recent advances in molecular genetic technology now allow the
consideration of NEW approaches to cancer treatment which circumvent these
problems. One example is the use of tissue specific promoters and enhancers
to regulate selectively the expression of inserted genes coding for cytotoxic
molecules, such as the A subunit of diphtheria toxin. Another strategy is the
use of gene splicing to produce hybrid molecules consisting of segments of
toxins and cell surface receptor ligands or the variable region of
immunoglobulins. These agents target cells at the level of the plasma
membrane. The success of these approaches for the specific killing of tumor
cells depend upon the identification of either unique regulatory regions for a
specific tumor gene or tumor specific surface receptor ligands.
RESEARCH GOALS AND SCOPE
Recent experiments have shown that specific cell targeting using gene transfer
or genetically engineered molecules can result in selective toxicity in vitro.
However, successful use of these techniques for the treatment of cancer
patients will depend upon the efficient delivery of the genes or toxic
molecules to the tumor in vivo, the expression of the genes within the cells
of the tumor, and the limitation of gene expression or ligand binding in
non-target tissues. This Program Announcement encourages novel approaches to
specific cancer cell targeting using recombinant DNA technology. Construction
of appropriate molecules or genes which would specifically alter the function
of tumor cells is encouraged. Proposed studies could include the isolation of
cell-specific genes with unique promoter and enhancer regions, the design of
multifunctional proteins with specific cell surface receptor ligands, or the
development of theoretical models which predict functionality of the
molecules. These molecules or genes should then be tested for efficacy in
vivo in appropriate tumor-bearing animal models addressing questions of
delivery and specificity. The overall aim of this initiative is the
stimulation of new therapeutic approaches to cancer using molecular genetic
technology which can be tested in a relevant experimental animal model.
Although outside the scope of this Program Announcement, resources are
available within the BRMP and DTP to facilitate further development of
interesting and efficacious therapeutic agents. Resources include scale-up
production, pharmacokinetic assessment, toxicology studies and clinical
evaluation of the agent.
MECHANISM OF SUPPORT
This program will be supported through traditional research grants (R01).
Awards may be made to public, private non-profit, and for-profit
organizations. All PHS and NIH grant policies will apply to applications
received in response to this announcement.
REVIEW PROCEDURES AND CRITERIA
Grant applications in response to this announcement will be reviewed in
accordance with the usual National Institutes of Health peer review (Study
Section) procedures. They will first be reviewed for scientific and technical
merit by a review group composed primarily of non-Federal scientific
consultants. Following the initial review, the applications will be evaluated
by the appropriate advisory Board or Council. Review criteria include:
o the significance and originality of the research from a scientific
and technical viewpoint.
o feasibility of research and adequacy of experimental design.
o adequacy of time which the investigator(s) and staff would devote
to the proposed studies.
o the experience, training and research competence of the
investigators.
o adequacy of available facilities.
o provision for the adequate protection of human subjects and the
humane treatment of animals.
Vol. 18, No. 6, February 24, 1989 - Page 5
The Study Section will review the requested budget and recommend an
appropriate budget for each approved application.
METHOD OF APPLYING
Applications should be submitted on Form PHS-398, revised 9/86, available in
the business or grants office at most academic or research institutions, or
from the Division of Research Grants, National Institutes of Health.
Applications will be accepted in accordance with the dates for receipt of new
applications on an indefinite basis:
February 1, June 1, October 1
The phrase "Specific Cancer Cell Targeting Using Molecular Genetic Technology"
should be typed on line 2 of the face page of the application. The original
and six copies should be sent or delivered to:
Grant Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892-4500**
In order to alert the DTP and BRMP to the submission of applications with
primary thrust directed to cancer treatment research, a copy of the face page
and abstract - key personnel page of the application should be sent under
separate cover to:
Dr. George S. Johnson
Grants and Contracts Operations Branch
Developmental Therapeutics Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Suite 832
Bethesda, Maryland 20892
Telephone: (301) 496-8783
*This program is described in the Catalog of Federal Domestic Assistance No.
13.395, Cancer Treatment Research. Awards are under authorization of the
Public Health Service Act, Section 301(c) and Section 402 (Public Law 78-410,
as amended; 42 USC 421; 42 USC 282) and administered under PHS grant policies
and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is
not subject to the intergovernmental review requirements of Executive Order
12372 or Health Systems Agency Review.