# Local blockade of IL10R on innate immune cells to mediate both innate and adaptive anti-tumor immunity

> **NIH NIH K08** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $263,034

## Abstract

PROJECT SUMMARY
Immune checkpoint blockade (ICB) has improved outcomes for patients with various malignancies by
disinhibiting anti-tumor T cells; however, most cancer patients do not yet benefit from it. In situ vaccination
(ISV), which converts tumors into therapeutic vaccines via direct intratumoral treatment, is under investigation
as a means of potentiating ICB. ISV often consists of injecting tumors with agents that activate stimulatory
receptors on antigen presenting cells (APCs). However, this method of ISV has not yet been translated into
standard-of-care treatments for most cancer patients. This may be, in part, because of the secretion of
inhibitory cytokines such as IL10 that confer negative feedback in response to ISV, and thus represent a critical
barrier to progress in this field. Preliminary data in this proposal suggest that by incorporating an IL10 receptor-
blocking antibody (αIL10R) into ISV, tumor control is significantly improved. These data further suggest that
αIL10R enhances tumor control by two distinct mechanisms, and support the central hypothesis that αIL10R
enhances innate immune cells' ability to control tumors, in various in situ vaccines, by both a direct and an
indirect mechanism. The objective of this proposal is to interrogate this central hypothesis through the
proposed Specific Aims.
This work will provide ideal training for the candidate as he prepares for his long-term career goal of
investigating the mechanisms by which innate immune cells can enhance the efficacy of cancer
immunotherapy. Memorial Sloan Kettering Cancer Center has a renowned immunology program. Dr. Jedd
Wolchok, the candidate's mentor, is a leader in the development of new immunotherapies, and the candidate's
co-mentors are experts on distinct aspects of innate immune cell biology. All have strong track records of
mentoring independent scientists. Together with the candidate and an interdisciplinary advisory committee,
they have formulated a rigorous training plan designed to increase the candidate's knowledge base in (i) innate
immunity, (ii) bioinformatics, especially regarding single-cell data, (iii) statistics, and (iv) practical skills related
to professional development. Training in these areas will occur through formal coursework, workshops, and
meetings with mentors and the advisory committee, who will evaluate the candidate's progress. This research
project and training plan will provide the foundation for the candidate to transition to a tenure-track position
leading an academic laboratory that is well positioned to compete for R01 funding. The candidate's ultimate
aim is to define new ways to enhance immunotherapy through the innate immune system, and thereby extend
life for patients with a range of solid cancers.

## Key facts

- **NIH application ID:** 10401840
- **Project number:** 5K08CA248964-03
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Danny Khalil
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $263,034
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401840

## Citation

> US National Institutes of Health, RePORTER application 10401840, Local blockade of IL10R on innate immune cells to mediate both innate and adaptive anti-tumor immunity (5K08CA248964-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10401840. Licensed CC0.

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