# Ex Vivo Profiling of Immunotherapy Combinations Using Organotypic Tumor Spheroids

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $189,130

## Abstract

PROJECT SUMMARY
 Precision cancer medicine currently focuses on knowledge of the cancer mutation repertoire and the
tailored application of drugs that target altered genes or pathways in individual patients, such as use of BRAF
inhibitors in patients with BRAF mutant melanoma. Immune checkpoint inhibitors targeting the PD-1/PD-L1
pathway have shown dramatic and durable clinical responses in melanoma and others cancers, but robust
predictive biomarkers are lacking and innate resistance is common. Thus, a critical need exists for more
sophisticated ex vivo functional testing modalities that recapitulate human tumor biology to predict response to
targeted and immune-based therapies to develop personalized treatment plans in real-time. We recently
developed a novel approach for evaluating ex vivo response to ICB using murine- and patient-derived
organotypic tumor spheroids (MDOTS/PDOTS) cultured in a 3-dimensional microfluidic system (Jenkins et al.,
Nature, under review). We demonstrated that spheroids isolated from fresh mouse and human tumor samples
retain autologous lymphoid and myeloid cell populations, including antigen-experienced tumor infiltrating CD4
and CD8 T lymphocytes, and respond to ICB in short-term ex vivo culture. Improved understanding of the
immune and tumor response to immune checkpoint inhibitors within the tumor microenvironment will facilitate
efforts to identify predictive biomarkers/models for immune checkpoint blockade in real-time, as well as future
efforts to screen for therapeutic combinations that enhance the response to immune checkpoint blockade, and
may ultimately provide a platform for the `personalization' of immunotherapy.
 I am currently a Clinical Fellow in Medicine in the Dana-Farber/Harvard Cancer Center Hematology-
Oncology Fellowship Program. Over 80% of my time is devoted to my ongoing research under the mentorship
of Dr. David A. Barbie (DFCI, Broad Institute). The remainder of my time is devoted to clinical practice and clinical
training, working primarily at the MGH Cancer Center in the Center for Melanoma. My goal is to successfully
transition from senior fellow to research instructor, and ultimately to an independent investigator in a tenure-track
position. I am applying for the K08 Mentored Clinical Scientist Research Career Development Award to provide
the necessary training and funding support to achieve this goal. Under the mentorship of Drs. Barbie and
Flaherty, and the guidance of my advisory committee (Drs. Wong, Janne, and Fisher), I will access to the
necessary resources and training to develop a successful, independent research program over the funding
period of the award.

## Key facts

- **NIH application ID:** 10459409
- **Project number:** 5K08CA226391-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Russell William Jenkins
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $189,130
- **Award type:** 5
- **Project period:** 2018-08-16 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459409

## Citation

> US National Institutes of Health, RePORTER application 10459409, Ex Vivo Profiling of Immunotherapy Combinations Using Organotypic Tumor Spheroids (5K08CA226391-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10459409. Licensed CC0.

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