# Immune Targeting of non-Hodgkin Lymphoma through Integrative Antigen Presentation Profiling

> **NIH NIH K08** · STANFORD UNIVERSITY · 2020 · $173,532

## Abstract

SUMMARY/ABSTRACT: Dr. Michael Khodadoust is an Instructor in Oncology at Stanford University. He and
his mentors, Drs. Ash Alizadeh and Ronald Levy, have developed a comprehensive career development plan
designed to prepare him for his long term goal of an independent career in translational studies of immunotherapy
in non-Hodgkin lymphoma (NHL).
The Applicant: Dr. Khodadoust has consistently pursued his goal of an academic career in translational
oncology. He completed his MD/PhD training in Immunology at the University of Michigan Medical School
discovering oncogenic functions of the DEK gene. More recently, Dr. Khodadoust applied a novel approach
integrating genomic and proteomic data to profile mantle cell lymphoma (MCL) tumor antigens, revealing that
the lymphoma immunoglobulin is a key antigen that is almost exclusively presented by class II MHC.
Mentorship Environment and Career Development Plan: Both mentors are practicing physician-scientists
with a history of providing seminal contributions to the understanding and treatment of NHL. Training will be
focused in developing a foundation in computational aspects of immunology and enhancing prior immunology
training. There will be specific practical training in T cell engineering with transgenic T cell receptors as a means
to translate antigen profiling results into future clinical therapies. The plan incorporates didactic courses, seminar
series, and participation in formal training programs, both internal and external to Stanford University. A
distinguished advisory committee consisting of Drs. Mark Davis, Crystal Mackall, and Philip Greenberg will
closely assist in training and mentorship.
Research: The key antigens that determine immune recognition of NHL remain unknown. We have developed
an innovative strategy to uncover novel tumor antigens, incorporating genomic and proteomic profiling to identify
peptides presented by the major histocompatibility complex (MHC) of cancer cells. This approach was designed
to specifically include patient-specific antigens including neoantigens. In preliminary work with MCL, we have
discovered that the only presented neoantigens were derived from unique lymphoma immunoglobulin VDJ
rearrangements and somatic hypermutation events. In the first aim, we now propose to extend this analysis to
other more common subtypes of NHL including diffuse large B cell lymphoma, follicular lymphoma, chronic
lymphocytic leukemia, marginal zone lymphoma, and Sezary syndrome. In the second aim, we will focus on
identifying T cell receptors (TCRs) specific for common NHL shared immunoglobulin-derived antigens. These
lymphoma-specific TCRs will be delivered into patient T cells and tested for cytolytic activity against primary
lymphoma cells as a proof of principle for future T cell-based therapies targeting the lymphoma immunoglobulin.

## Key facts

- **NIH application ID:** 9854897
- **Project number:** 5K08CA207882-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michael Siavash Khodadoust
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $173,532
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854897

## Citation

> US National Institutes of Health, RePORTER application 9854897, Immune Targeting of non-Hodgkin Lymphoma through Integrative Antigen Presentation Profiling (5K08CA207882-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9854897. Licensed CC0.

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