R01CA293908
Project Grant
Overview
Grant Description
Combinatorial application of nanoscale technologies to target a novel mechanism of immune evasion by cancer cells - project summary
Immunotherapy holds the promise of a cure for cancer. However, only a subset (<20%) of patients exhibit durable response to immunotherapy. This is because immune checkpoint inhibitors need immune cells in the tumor.
However, many tumors are found to be immunologically barren or cold, i.e. lack tumor infiltrating lymphocytes (TILs). Overcoming this barrier is key to a cure for cancer.
We recently discovered that cancer cells form physical nanoscale tentacles (tunneling nanotubes) to connect with and harvest mitochondria from immune cells, which depletes the immune cells.
Recent evidence show mitochondria-harvesting tumors have poor clinical outcomes. There is is an unmet need to target this novel mechanism of immune evasion.
There are two distinct and complementary strategies to achieve this goal: (1) engineer CAR-Ts or TILs with extra mitochondria (augmented T cells) such that any loss of mitochondria to cancer cells doesn’t not fully deplete the immune cells of their metabolic capacity; and (2) disable the ability of a cancer cell to form nanotubes to harvest immune cell mitochondria.
In this proposal, we aim to develop an immunotherapeutic regimen that combines these two strategies with an immune checkpoint inhibition. Specifically, we will evaluate different organelle transplantation technologies for delivering mitochondria, a nanoscale structure, to a T cell ex vivo prior to infusion as cell therapy (Aim 1); (2) test the antitumor efficacy of these mitochondria-augmented T cells in combination with a drug that inhibits the capability of cancer cells to form nanotubes and an immune checkpoint inhibitor (Aim 2); and dissect the mechanisms underlying mitochondrial harvesting (Aim 3).
These studies can lead to paradigm shift in immunotherapy and generate fundamental insights into cancer-immune cell communications at the nanoscale.
Immunotherapy holds the promise of a cure for cancer. However, only a subset (<20%) of patients exhibit durable response to immunotherapy. This is because immune checkpoint inhibitors need immune cells in the tumor.
However, many tumors are found to be immunologically barren or cold, i.e. lack tumor infiltrating lymphocytes (TILs). Overcoming this barrier is key to a cure for cancer.
We recently discovered that cancer cells form physical nanoscale tentacles (tunneling nanotubes) to connect with and harvest mitochondria from immune cells, which depletes the immune cells.
Recent evidence show mitochondria-harvesting tumors have poor clinical outcomes. There is is an unmet need to target this novel mechanism of immune evasion.
There are two distinct and complementary strategies to achieve this goal: (1) engineer CAR-Ts or TILs with extra mitochondria (augmented T cells) such that any loss of mitochondria to cancer cells doesn’t not fully deplete the immune cells of their metabolic capacity; and (2) disable the ability of a cancer cell to form nanotubes to harvest immune cell mitochondria.
In this proposal, we aim to develop an immunotherapeutic regimen that combines these two strategies with an immune checkpoint inhibition. Specifically, we will evaluate different organelle transplantation technologies for delivering mitochondria, a nanoscale structure, to a T cell ex vivo prior to infusion as cell therapy (Aim 1); (2) test the antitumor efficacy of these mitochondria-augmented T cells in combination with a drug that inhibits the capability of cancer cells to form nanotubes and an immune checkpoint inhibitor (Aim 2); and dissect the mechanisms underlying mitochondrial harvesting (Aim 3).
These studies can lead to paradigm shift in immunotherapy and generate fundamental insights into cancer-immune cell communications at the nanoscale.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Boston,
Massachusetts
021156110
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 400% from $690,825 to $3,454,125.
Brigham & Womens Hospital was awarded
Nanoscale Technology Targeting Cancer Cell Immune Evasion
Project Grant R01CA293908
worth $3,454,125
from National Cancer Institute in June 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 Innovative Research in Cancer Nanotechnology (IRCN; R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 6/22/26
Period of Performance
6/21/24
Start Date
5/31/29
End Date
Funding Split
$3.5M
Federal Obligation
$0.0
Non-Federal Obligation
$3.5M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01CA293908
Additional Detail
Award ID FAIN
R01CA293908
SAI Number
R01CA293908-677399028
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
QN6MS4VN7BD1
Awardee CAGE
0W3J1
Performance District
MA-07
Senators
Edward Markey
Elizabeth Warren
Elizabeth Warren
Modified: 6/22/26