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

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $340,336

## Abstract

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.

## Key facts

- **NIH application ID:** 10072045
- **Project number:** 5R01CA247632-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Darrell J Irvine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $340,336
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072045

## Citation

> US National Institutes of Health, RePORTER application 10072045, Enhancing CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor (5R01CA247632-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072045. Licensed CC0.

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