Monday, June 30, 2025 6/30/2025

Enhancing CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor

Award Number: R01CA247632
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

Group Awards By:

View Award Description

Enhancing CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor - Project Summary/Abstract 30 lines or less: Adoptive cell therapy (ACT) with chimeric antigen receptor (CAR) T cells has shown dramatic clinical responses in hematologic cancers, with a high proportion of durable complete remissions elicited in leukemias and lymphomas. This success has led to a strong commercial investment establishing adoptive cell therapy as a viable clinical therapy and the first licensure of CAR-T therapy by the FDA in 2017. However, achieving the full promise of CAR-T ACT, especially in solid tumors, will require further advances in this form of cellular therapy. A key challenge is maintaining a sufficient pool of functional CAR-T cells in vivo. In addition, even in hematologic tumors treated effectively with CAR T cells, chemotherapeutic lymphodepletion regimens with high toxicity are often required to ensure the engraftment and initial expansion of the donor cells. We recently discovered an efficient strategy for molecularly targeting peptide vaccines and vaccine adjuvants to lymph nodes, through the use of albumin-binding phospholipid-polymer linkers conjugated to antigens/molecular adjuvants. Albumin constitutively traffics from blood to lymph, and serves as an effective chaperone to concentrate these “amphiphile-vaccine” (amph-vax) components in lymph nodes that would otherwise be rapidly dispersed in the bloodstream following parenteral injection. However, these lipid-polymer conjugates also exhibit the property that they insert in cell membranes on arrival in lymph nodes. We propose here to exploit these dual lymph node targeting and membrane-decorating properties of amph-vax molecules to create a booster vaccine for CAR T cells, which can be used to repeatedly expand and rejuvenate CAR-T directly in vivo- in native lymph nodes and/or tumors. To evaluate this approach in the presence of a complete host immune system, we will test this concept both with human T cells and with an immunocompetent syngeneic mouse model of melanoma recently developed by our lab. Our specific aims are to (1) Characterize the biology of synthetic antigen presentation of amphiphile-ligands from the surface of antigen presenting cells to CAR T cells in vivo, (2) to demonstrate an amph-vax design generalizable to any CAR, (3) to evaluate the capacity of a CAR-T vaccine to expand T cells with enhanced functionality and persistence in vivo, and (4) to test the utility of intratumoral amph-vax delivery to enhance CAR-T and endogenous T cell priming in tandem. These studies will establish a robust technology platform to transform multiple aspects of adoptive cell therapy and address key limitations in existing ACT therapeutic strategies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	5	4/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $321,825 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	001	5	4/18/2024	NON-COMPETING CONTINUATION	$16,939
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	5	12/15/2023	NON-COMPETING CONTINUATION	$304,886
														Subtotal = $321,825

Issue Date FY: 2023 ( Subtotal = $331,987 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	001	4	3/15/2023	NON-COMPETING CONTINUATION	$27,101
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	4	12/12/2022	NON-COMPETING CONTINUATION	$304,886
														Subtotal = $331,987

Issue Date FY: 2022 ( Subtotal = $331,987 )
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	001	3	6/10/2022	NON-COMPETING CONTINUATION	$27,101
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	3	12/14/2021	NON-COMPETING CONTINUATION	$304,886
														Subtotal = $331,987

Issue Date FY: 2021 ( Subtotal = $340,336 )
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	001	2	1/26/2021	NON-COMPETING CONTINUATION	$17,018
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	2	12/29/2020	NON-COMPETING CONTINUATION	$323,318
														Subtotal = $340,336

Issue Date FY: 2020 ( Subtotal = $348,609 )
2020	2020	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	1	12/16/2019	NEW	$348,609
														Subtotal = $348,609

Grand Total All Awards = $1,674,744

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Enhancing CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor

Award Number: R01CA247632

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer