# Reprogramming the chimeric antigen receptor T cell epigenome to augment anti-tumor activity

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $192,138

## Abstract

PROJECT SUMMARY/ABSTRACT
The candidate for this NCI Career Development Award is Max Jan, MD, PhD, who has completed clinical training
in molecular genetic pathology and is a current postdoctoral researcher at Massachusetts General Hospital
(MGH). Dr. Jan has joined the laboratory of Benjamin Ebert, a worldwide leader in the study of hematologic
malignancies and targeted protein degradation as a therapeutic concept in cancer. Dr. Jan is co-mentored by
Marcela Maus, a worldwide leader in the field of cellular immunotherapy. An immediate-term goal for the
candidate is to complete his proposed scientific Aims, which center around reprogramming the epigenome of
chimeric antigen receptor (CAR) T cells in order to increase their anti-tumor activity. The proposed work will
address a fundamental limitation of immune cell therapies for cancer, that cancers are too often able to evade
such therapies by inducing immune cell dysregulation and suppression. The candidate will develop methods to
reprogram the CAR T cell epigenome to enhance persistence and anti-tumor activity (Aim 1). A chemical biology
approach will then be used to switch between baseline and reprogrammed epigenetic states, in order to study
the immediate and direct mechanisms governing this process (Aim 2). Finally, the impact of regulated, switchable
epigenomic reprogramming on long-term CAR T cell effector functions will be tested (Aim 3). The completion of
these aims will intellectually and technically prepare Dr. Jan to transition to independence. The candidate’s short-
and long-term goals are directly relevant to the mission of the NCI, and pursue scientific knowledge in order to
more successfully treat patients with cancer using immune cell therapies. In the long term, the candidate will
continue to study patient responses to immune therapy in order to engineer next generations of safer and more
effective cellular immunotherapies for patients with solid and blood cancers. The candidate has advanced a
mentored career development plan centered on technical training in single cell genomics and epigenetics, as
well as academic and leadership skills. The candidate has outstanding institutional and departmental support at
MGH, where he has full access to excellent technical and intellectual resources. The candidate receives
enthusiastic support from his prior and current mentors, who have outstanding track records for training
physician-scientist to become independent investigators. Finally, the candidate has developed a scientific
advisory committee composed of highly regarded physician-investigators in the relevant areas of cancer
immunology and genomics who will provide experienced and sure-handed mentorship. This career development
award will greatly enhance Max Jan’s transition to independence as an investigator dedicated to the study of
immune therapies to improve the lives of people with cancer.

## Key facts

- **NIH application ID:** 10105416
- **Project number:** 1K08CA255932-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Max Jan
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,138
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105416

## Citation

> US National Institutes of Health, RePORTER application 10105416, Reprogramming the chimeric antigen receptor T cell epigenome to augment anti-tumor activity (1K08CA255932-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10105416. Licensed CC0.

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