R01CA294793
Project Grant
Overview
Grant Description
Elucidating resistance mechanisms and enhancing response to immune checkpoint blockade in central nervous system metastases from breast cancer - Project summary
Metastases to the central nervous system (CNS) are a common complication of breast cancer.
Prognosis is typically on the order of a few months.
Immunotherapies have revolutionized the management of many types of cancers.
However, these agents have not been systematically studied in the management of CNS metastases from breast cancer.
We are conducting several Phase II trials to explore the role of newly developed immunotherapies in CNS metastases.
Three of our trials have already met primary endpoint, with a subset of patients with breast cancer showing responses to immunotherapy.
We propose to study cancer genetic and immune phenotypic changes in samples collected from patients before, during and after immunotherapy.
Our overarching objective is to characterize mechanisms of resistance to immunotherapy in CNS metastases.
To achieve this, we will chart the co-evolution of cancer and the immune system over time and anatomical location during immunotherapy by profiling DNA and RNA from cancer tissues, peripheral blood, and cerebrospinal fluid (CSF).
Notably, using cutting-edge single-cell technologies, we will examine alterations to the cancer genome and immune cell behaviors at unprecedented resolution.
Furthermore, in our innovative mouse models of brain metastases, we will study novel combination therapies, including CDK inhibition with immune-checkpoint blockade, to augment the efficacy of immunotherapy.
We believe that this work has the potential to uncover basic mechanisms of treatment-failure in these patients and that these discoveries will have tremendous translational potential as a basis on which to refine existing immunotherapy protocols and develop novel treatment strategies.
Metastases to the central nervous system (CNS) are a common complication of breast cancer.
Prognosis is typically on the order of a few months.
Immunotherapies have revolutionized the management of many types of cancers.
However, these agents have not been systematically studied in the management of CNS metastases from breast cancer.
We are conducting several Phase II trials to explore the role of newly developed immunotherapies in CNS metastases.
Three of our trials have already met primary endpoint, with a subset of patients with breast cancer showing responses to immunotherapy.
We propose to study cancer genetic and immune phenotypic changes in samples collected from patients before, during and after immunotherapy.
Our overarching objective is to characterize mechanisms of resistance to immunotherapy in CNS metastases.
To achieve this, we will chart the co-evolution of cancer and the immune system over time and anatomical location during immunotherapy by profiling DNA and RNA from cancer tissues, peripheral blood, and cerebrospinal fluid (CSF).
Notably, using cutting-edge single-cell technologies, we will examine alterations to the cancer genome and immune cell behaviors at unprecedented resolution.
Furthermore, in our innovative mouse models of brain metastases, we will study novel combination therapies, including CDK inhibition with immune-checkpoint blockade, to augment the efficacy of immunotherapy.
We believe that this work has the potential to uncover basic mechanisms of treatment-failure in these patients and that these discoveries will have tremendous translational potential as a basis on which to refine existing immunotherapy protocols and develop novel treatment strategies.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Boston,
Massachusetts
021142621
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 397% from $701,408 to $3,485,673.
The General Hospital Corporation was awarded
Enhancing Immunotherapy Efficacy for CNS Breast Cancer Metastases
Project Grant R01CA294793
worth $3,485,673
from National Cancer Institute in July 2024 with work to be completed primarily in Boston Massachusetts United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.395 Cancer Treatment Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 7/6/26
Period of Performance
7/12/24
Start Date
6/30/29
End Date
Funding Split
$3.5M
Federal Obligation
$0.0
Non-Federal Obligation
$3.5M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01CA294793
Additional Detail
Award ID FAIN
R01CA294793
SAI Number
R01CA294793-3946135263
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75NC00 NIH National Cancer Institute
Funding Office
75NC00 NIH National Cancer Institute
Awardee UEI
FLJ7DQKLL226
Awardee CAGE
0ULU5
Performance District
MA-08
Senators
Edward Markey
Elizabeth Warren
Elizabeth Warren
Modified: 7/6/26